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Artificial rearing of low birth-weight pigs Whiting, Richard John 1982

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ARTIFICIAL REARING OF LOW BIRTH-WEIGHT PIGS  by  RICHARD JOHN WHITING Sc. Ag., The U n i v e r s i t y o f B r i t i s h Columbia, 1970  A THESIS SUBMITTED IN PARTIAL FULFILMENT OF THE REQUIREMENTS FOR THE DEGREE OF MASTER OF SCIENCE  in THE FACULTY OF GRADUATE STUDIES (Department o f Animal S c i e n c e )  We a c c e p t t h i s  t h e s i s as conforming  to the r e q u i r e d  standard  THE UNIVERSITY OF BRITISH COLUMBIA May 1982  ©  R i c h a r d John W h i t i n g , 1982  In p r e s e n t i n g  t h i s t h e s i s i n p a r t i a l f u l f i l m e n t o f the  requirements f o r an advanced degree a t the U n i v e r s i t y o f B r i t i s h Columbia, I agree t h a t the L i b r a r y s h a l l make it  freely  a v a i l a b l e f o r reference  and study.  I further  agree t h a t p e r m i s s i o n f o r e x t e n s i v e copying o f t h i s  thesis  f o r s c h o l a r l y purposes may be granted by t h e head o f my department o r by h i s o r her r e p r e s e n t a t i v e s . understood t h a t copying o r p u b l i c a t i o n o f t h i s for  financial  gain  A/"Wy*»(  The U n i v e r s i t y o f B r i t i s h 1956 Main Mall Vancouver, Canada V6T 1Y3  DE-6 (3/81)  thesis  s h a l l n o t be allowed without my  permission.  Department o f  It is  ^ <X~*ir~L*t Columbia  written  ABSTRACT Four e x p e r i m e n t s were conducted to e v a l u a t e a c r u d e immunoglobulin p r e p a r a t i o n f r a c t i o n a t e d from a b a t t o i r w i t h ammonium s u l p h a t e .  p o r c i n e serum  The p r e p a r a t i o n was used as an a d d i t i v e  to  m i l k r e p l a c e r f o r c o l o s t r u m d e p r i v e d , low b i r t h - w e i g h t p i g s r e a r e d i n a n o n - i s o l a t e d environment. e x p e r i m e n t s 1 and 3 .  S i x p i g s per t r e a t m e n t were used i n  E i g h t p i g s per t r e a t m e n t were used i n e x p e r i -  ments 2 and 4 . In the f i r s t e x p e r i m e n t , members of the n e g a t i v e  control  group d i d not s u r v i v e and m o r t a l i t y o f the o t h e r t h r e e groups which r e c e i v e d some immunity was h i g h . negative control  In the second e x p e r i m e n t ,  group was e l i m i n a t e d from t h e t r i a l ,  the  so t h o s e r e c e i v -  i n g o n l y c o l o s t r u m f o r 12 hours d i e d , but t h e two groups r e c e i v i n g immunoglobulin t r e a t m e n t showed improved s u r v i v a l  ( 6 3 , 50%).  In  the  t h i r d e x p e r i m e n t , h i g h e r l e v e l s o f immunoglobulin ( 1 5 g . / k g . body weight, i n i t i a l l y e f f e c t on s u r v i v a l to 2 g . / k g . .  f o l l o w e d by 5 g . / k g / d a y ) d i d not show a s i g n i f i c a n t i n comparison w i t h the p r e v i o u s l e v e l s o f  lOg./kg.  However, r a t e o f g a i n i n body weight was s i g n i f i c a n t l y  h i g h e r i n the h i g h dose l e v e l o f  immunoglobulin.  In the f o u r t h e x p e r i m e n t the p i g s were m a i n t a i n e d on immunoglobulin f o r 1 0 , 1 5 , and 21 days and i t was found t h a t 21 day treatment e l i m i n a t e d deaths.  The h i g h e s t r a t e o f g a i n was a c h i e v e d  w i t h t h o s e on 21 day t r e a t m e n t i n experiment 4 . o f g a i n were c o n s i d e r a b l y below t h o s e a c h i e v e d  However, t h e s e r a t e s with Digs on the sow.  The causes o f m o r t a l i t y were p r e d o m i n a t e l y E . c o l i s c o u r s , s e p t i c a e m i a due t o E. c o l i and o t h e r b a c t e r i a , pneumonia, and 1n t h e ii  \n  two experiments, S a l m o n e l l o s i s . 4 by the immunoglobulin  The p r e v e n t i o n  o f death i n experiment  e x t r a c t , i n d i c a t e d the s u c c e s s o f the p r e p a r a t i o n  a g a i n s t the S a l m o n e l l a s p e c i e s  encountered.  iii  TABLE OF CONTENTS Page  1.  INTRODUCTION  1  2.  LITERATURE REVIEW  2  2.1 The Mammalian Immune System  2  2.1.1 The Development of Immunocytes  2  2.1.2 The Intestinal Secretory Immune System . . . .  4  2.1.3 Antibody  5  2.1.3.1 The Structure of Antibodies  5  2.1.4 Complement  10  2.1.5 Antibody Reactions in the Gut Associated Lymphoid Tissue (GALT)  13  2.2 Prenatal Development of the Porcine Immune System  .  16  2.3 Postnatal Development of the Porcine Immune System .  18  2.4 The "Runt" Phenomenon  .  23  2.5 Mechanisms of Action of Bacteria in the Intestine. .  26  2.6 Diarrhea in Piglets  28  2.7 Non-Specific Gastro-Intestinal Immune Mechanisms . .  30  2.7.1 The Gastric Trap  30  2.7.2 Intestinal Motility  30  2.7.3 Intestinal Microflora  31  2.7.4 Non-Immunological Factors in the Secretions of the G. I. Tract  32  2.8 Humoral and Cellular Immunity in Porcine Mammary Secretions  34  2.9 Preweaning Mortality  36  2.9.1 Causes of Preweaning Mortality iv  36  2 . 9 . 2 E f f e c t o f Low B i r t h - W e i g h t 3.  on S u r v i v a l  . . .  38  EXPERIMENTAL  42  3.1 I n t r o d u c t i o n  42  3.2 Experiment I  44  3.2.1 Objective  44  3 . 2 . 2 M a t e r i a l s and Methods  44  3 . 2 . 2 . 1 Experimental Animals  44  3.2.2.2 Preparation of Porcine Immunoglobulins  44  3 . 2 . 2 . 3 D i e t a r y Treatments  44  3 . 2 . 2 . 4 Feeding Regimen .  45  3 . 2 . 3 Measurments and O b s e r v a t i o n s  45  3 . 2 . 4 R e s u l t s and D i s c u s s i o n  46  3 . 3 Experiment II  49  3.3.1 Objective  49  3 . 3 . 2 M a t e r i a l s and Methods  49  3 . 3 . 2 . 1 E x p e r i m e n t a l Animals  49  3 . 3 . 2 . 2 D i e t a r y Treatments  49  3 . 3 . 2 . 3 Feeding Regimen  50  3 . 3 . 3 Measurments and O b s e r v a t i o n s  50  3 . 3 . 4 R e s u l t s and D i s c u s s i o n  51  3.4 Experiment I I I  54  3.4.1 Objective  54  3 . 4 . 2 M a t e r i a l s and Methods  54  3 . 4 . 2 . 1 Experimental Animals  54  3 . 4 . 2 . 2 D i e t a r y Treatments  54  v  3 . 4 . 2 . 3 F e e d i n g Regimen  55  3 . 4 . 3 Measurments and O b s e r v a t i o n s  55  3 . 4 . 4 R e s u l t s and D i s c u s s i o n  56  3.5 Experiment IV  64  3.5.1 Objective  64  3 . 5 . 2 M a t e r i a l s and Methods  64  3 . 5 . 2 . 1 E x p e r i m e n t a l Animals  64  3 . 5 . 2 . 2 D i e t a r y Treatments  64  3 . 5 . 2 . 3 F e e d i n g Regimen  65  3 . 5 . 3 Measurments and O b s e r v a t i o n s 3 . 5 . 4 R e s u l t s and D i s c u s s i o n  . . .  65 65  3.6 General D i s c u s s i o n  70  3.7 C o n c l u s i o n s  75  4 . BIBLIOGRAPHY  77  vi  LIST OF TABLES Table  Page  2.1  Immunoglobulin S t r u c t u r e  2.2  Mechanisms o f A n t i b o d y A n t i - B a c t e r i a l A c t i v i t y  2.3  P r e n a t a l Development o f the P o r c i n e Immune System  2.4  A Summary o f Major Causes C o n t r i b u t i n g t o Death i n  2.5  9 14 . . .  17  Baby P i g s  37  E f f e c t o f B i r t h Weight on M o r t a l i t y  39  3 . 1 a Experiment I:  Experimental Animals  47  3.1b Experiment I:  Results  47  3.2a Experiment I I :  Experimental Animals  52  3.2b Experiment I I :  Results  52  3 . 3 a Experiment I I I :  Experimental Animals  57  3.3b E x p e r i m e n t I I I :  Results  58  3 . 4 a Experiment I V : E x p e r i m e n t a l A n i m a l s  66  3.4b Experiment I V : R e s u l t s  66  vii  LIST OF FIGURES Figure 2.1  2.2 2.3  Page  The IgG A n t i b o d y M o l e c u l e : a Schematic P r e s e n t a t i o n of Structure A c t i v a t i o n Pathways and P h y s i o l o g i c a l F u n c t i o n s Complement Components  6  of 12  Serum Immunoglobulin P r o f i l e s o f the Neonatal P i g . . . 20  3 . 1 a Growth i n Experiment I I I ,  Replicate 1  60  3.1b Growth i n Experiment I I I ,  Replicate 2  61  3.2  S c o u r i n g Frequency  63  3.3  C u m u l a t i v e Weight G a i n : Experiment IV  68  3.4  Comparative Growth Curves  71  vi i i  ACKNOWLEDGMENTS I would l i k e t o g r a t e f u l l y acknowledge t h e wonderful p a t i e n c e and u n d e r s t a n d i n g  o f my p r o j e c t s u p e r v i s o r , Dr.B.D. Owen  who p r o v i d e d s t r o n g support d u r i n g some d i f f i c u l t p e r i o d s . I should a l s o l i k e t o thank Dr. R.M. Beames f o r h i s a s s i s t a n c e toward completion a s s i s t a n c e with s t a t i s t i c a l I am indebted in Abbotsford  o f t h e study.  Dr. R. P e t e r s o n  provided  analyses. t o t h e people  a t B.C. V e t e r i n a r y L a b o r a t o r y  f o r c a r r y i n g o u t a u t o p s i e s and b a c t e r i o l o g i c a l  assess-  ments. Finally,  I would l i k e t o express  thanks t o t h e t h r e e  summer s t u d e n t s , B r i g i t t e Sonendrucher, L a r r y N a u l t , and Don R o b e r t s , who helped d u r i n g odd hours o f t h e n i g h t and day t o c a r r y o u t t h e experiments.  ix  1  1.  INTRODUCTION S e v e r a l s t u d i e s have been done on the a r t i f i c i a l  rearing  o f n e o n a t a l p i g s u s i n g supplemental immunoglobulins added t o the  diet  (Owen, B e l l , and W i l l i a m s , 1 9 6 1 ; S c o o t , 1972; M c C a l l u m , 1977; Lodge and E l l i o t , 1979).  The e x p e r i m e n t s r e p o r t e d h e r e i n were attempts  to r a i s e  low b i r t h w e i g h t  p i g s , i n c l u d i n g s o - c a l l e d r u n t s , i n a f a r m environment  u s i n g p r e v i o u s l y s t u d i e d l e v e l s and p e r i o d s o f s e r u m - d e r i v e d immunoglobulin  supplementation. Below a b i r t h w e i g h t  d u r i n g the f i r s t week o f l i f e  o f 900 to 1000 grams, p i g  dramatically  mortality  i n c r e a s e s (Pomeroy, 1960;  S h a r p e , 1966; L e f c e , 1 9 7 1 ; Fahmy and B e r n a r d , 1 9 7 1 ; B e r e s k i n e t a l . , 1973; E n g l i s h and S m i t h , 1 9 7 5 ) .  P r e v i o u s workers have found  g i v e n an environment removed from c o m p e t i t i o n and t r a u m a , low w e i g h t p i g s can be a r t i f i c i a l l y  r e a r e d w i t h low m o r t a l i t y  s a t i s f a c t o r y growth r a t e s ( L e c c e , 1 9 7 1 ; E n g l a n d , 1 9 7 4 ) .  that, birth-  and more .However, these  e a r l i e r s t u d i e s u t i l i z e d a s e m i - i s o l a t e d environment and s t e r i l e f o o d . The current project  i n v o l v e d attempts  to r a i s e t h e s e low b i r t h w e i g h t  i n a n o n - i s o l a t e d environment u s i n g added immunoglobulins the need f o r an i s o l a t e d  environment.  to  pigs  eliminate  2 2.  LITERATURE REVIEW  2.1  The Mammalian Immune System  2.1.1  The Development o f  Immunocytes  The major e f f e c t o r c e l l s i n immunity a r e the l y m p h o c y t e s , o f w h i c h t h e r e a r e two c l a s s e s .  There a r e T lymphocytes where " T " r e f e r s  to  t h e i r d e r i v a t i o n i n the thymus g l a n d and t h e r e a r e B lymphocytes where the " B " r e f e r s t o the major d i f f e r e n t i a t i o n  r e g i o n i n the b i r d c a l l e d the Bursa  o f F a b r i c u s (Cooper and L a w t o n , 1 9 7 4 ) .  The bursa has no analogous r e g i o n y e t  demonstrated i n the mammal a l t h o u g h s i m i l a r development o f B c e l l s here seems t o o c c u r i n the f e t a l  l i v e r o r bone marrow.  (Cooper & Lawton 1 9 7 4 ) .  These  lymphocytes a r e d e r i v e d from a common stem c e l l f o r hemopoiesis from which other c i r c u l a t i n g c e l l s are d e r i v e d .  Thus, lymphocytes, monocytes, p o l y -  morphonuclear l e u c o c y t e s , macrophage? m e g a k a r y o c y t e s (from which  platelets  a r e d e r i v e d ) , mast c e l l s , e o s i n o p h i l s and e r y t h r o c y t e s a r e a l l d e r i v e d from the same stem c e l l . system.  A l l , e x c e p t e r y t h r o c y t e s , a r e i n v o l v e d i n the immune  The p r i m o r d i a l  stem c e l l f i r s t d e v e l o p s i n the b l o o d i s l a n d s o f  embryonic y o l k s a c and then m i g r a t e s to the l i v e r o f the f e t u s .  Later  the  in  g e s t a t i o n and d u r i n g a d u l t l i f e t h e s e stem c e l l s a r e found i n the bone marrow, h a v i n g m i g r a t e d from the f e t a l  l i v e r , and they c o n t i n u e the v e r y a c t i v e p r o -  cess o f hemopoiesis t h r o u g h o u t the l i f e o f t h e i n d i v i d u a l  (Hood e_t a_K, 1978).  In the h e m o p o i e t i c t i s s u e s a s u b t l e and as y e t differentiation  o c c u r s g i v i n g r i s e to c e l l s which w i l l  a s p e c i f i c t i s s u e microenvironment.  undetermined  i n d i v i d u a l l y home to  Here f u r t h e r d i f f e r e n t i a t i o n  and a  commitment o c c u r s which means t h a t the c e l l i s s e t on a u n i - d i r e c t i o n a l o f development.  path  T c e l l p r e c u r s o r s become committed i n the microenvironment  o f the thymus under the c o n t r o l o f thymus hormone; B c e l l s a r e committed  in  the fetal l i v e r , bone marrow and, possibly Peyer's patches (Bienstock, 1979); macrophages and polymorphonuclear leucocytes in the bone marrow and spleen; and mast cells in the bone marrow (Hood et aj_., 1978). The lymphocytes develop within these specific tissues in an antigen independent differentiation until they are capable of responding to antigens.  At this stage both B and T cells carry antigen receptor molecules  on their membranes.  The B cell receptor molecule is an immunoglobulin. The  T cell receptor molecule is as yet unidentified but does not seem to be immunoglobulin (Benaceraf and Unanue, 1979).  The B cell immunoglobulin is  f i r s t IgM but later bears the isotype to be produced by the end cells.  (Hood  et a l . , 1978). If these lymphocytes bind a cognate antigen to these surface receptors they become activated; they enlarge with the formation of polysomes, microtubules and macromolecules in a process called blast transformation (Hood et a l . , 1978).  These activated cells proliferate and continue to differentiate.  Thus clones of T cells are formed containing both effector cells and memory T cells.  Similarly, clones of effector and memory B cells are formed.  The memory  cells remain in circulation and provide a continuously reactive clone of cells which respond in a secondary immune response upon later antigen stimulation. The major effector cells are directly involved in antibody production as with T helper and T suppressor and plasma cells (B end cells) or in cell mediated immunity as with T k i l l e r and T - delayed hypersensitivity cells.  (Hood et  a l . , 1978). The function of the lymphoid system is to provide maximal contact of any antigen with its repertoire of antigen specific lymphocytes. Foreign material is phagocytized by macrophages which present antigen from  4 the f o r e i g n m a t e r i a l  to the T c e l l s .  These T c e l l s (T h e l p e r s ) a r e then  a c t i v a t e d and s t i m u l a t e maximal a n t i b o d y p r o d u c t i o n by t h e plasma c e l l s . Any a n t i g e n w h i c h e n t e r s t i s s u e i s g a t h e r e d i n t o the l y m p h a t i c system by the lymph f l u i d and c a r r i e d t o a nearby f i l t e r i n g lymph node o r t h e s p l e e n to stimulate antibody production. t r a c t or g a s t r o - i n t e s t i n a l s p e c i a l i z e d organs:  A n t i g e n s which e n t e r the upper  t r a c t e n c o u n t e r l o c a l lymph nodes as w e l l as  t o n s i l s , a d e n o i d s , P e y e r ' s p a t c h e s , and the a p p e n d i x .  B l o o d borne a n t i g e n s a r e d e a l t w i t h m a i n l y by the s p l e e n . 2.1.2  respiratory  The I n t e s t i n a l  (Hood e t a l . , 1978),  S e c r e t o r y Immune System  A major a r e a o f c o n t a c t w i t h a n t i g e n i c m a t e r i a l ment i s a t the mucosal l i n i n g o f t h e g a s t r o - i n t e s t i n a l  system.  i n the e n v i r o n Consequent t o  the development o f g u t m i c r o f l o r a , the l a m i n a o f t h e gut becomes i n f i l t r a t e d w i t h immunocytes p r o d u c i n g p r e d o m i n a t e l y IgM and IgA which a r e a c r o s s the gut e p i t h i l i u m i n t o t h e lumen ( P o r t e r e t a l _ . , 1 9 7 6 ) .  transported Initially  i n the development o f a young animal IgM p r o d u c i n g c e l l s predominate  but  l a t e r t h e r e i s a g r e a t e r p r o l i f e r a t i o n o f IgA c e l l s ( A l l e n and P o r t e r , 1 9 7 3 ) . The i n t e s t i n a l  t r a c t i s e s p e c i a l l y adapted f o r p r o d u c t i o n  of  a n t i b o d y to the l u m e n a l l y o c c u r r i n g a n t i g e n s o f b a c t e r i a , v i r u s e s , and o t h e r food borne m a t e r i a l s .  The mucosa o v e r l y i n g the P e y e r ' s patches appears to  be adapted to the uptake o f l a r g e m o l e c u l e s and even i n t a c t m i c r o o r g a n i s m s (McClelland, 1979).  I n t h i s way p r e c u r s o r lymphocytes a r e s e n s i t i z e d i n  t h e P e y e r ' s p a t c h e s and a r e r e l e a s e d t o c i r c u l a t e and home i n t o the  intestinal  l a m i n a p r o p r i a where t h e y d e v e l o p i n t o IgA s e c r e t i n g plasma c e l l s ( P i e r c e and Cowans, 1975; H a s l a n d e t a l _ . , 1 9 7 6 ) . The development o f a s y s t e m i c a n t i b o d y p r o d u c t i o n due t o gastro-intestinal  the  i m m u n i z a t i o n r o u t e may a l s o o c c u r from IgG o r IgM forming  5 c e l l s which a r e seeded by P e y e r ' s patches i n e x t r a - i n t e s t i n a l tissues.  A l s o t h e r e i s the p o s s i b i l i t y o f a n t i g e n r e a c h i n g lymphocytes  i n the s p l e e n o r p e r i p h e r a l 1971).  lymphoid  lymph nodes from the gut ( C r a i g and C e b r a ,  Serum IgA a l s o o r i g i n a t e s from g a s t r o i n t e s t i n a l  secretion  (Tomasi, 1976). Mammary s e c r e t i o n s o f a n t i b o d y a r e found t o be s e n s i t i z e d to i n t e s t i n a l  a n t i g e n s ( C h i d l o w and P o r t e r , 1 9 7 9 ) .  mammary a x i s r e f e r r e d t o by Parmely e t a K , ( 1 9 7 6 ) . cytes, possibly originating  T h i s i s the g u t - t o IgA s e c r e t i n g lympho-  i n P e y e r ' s patches and t r a v e l l i n g  through  the  m e s e n t e r i c lymph nodes i n t o c i r c u l a t i o n a r e t r a p p e d by a c t i v e mammary t i s s u e under the i n f l u e n c e o f mammotropic hormones (Lamm e t a l _ . , 1 9 7 8 ) . 2.1.3  Antibody A n t i b o d y i s produced by plasma c e l l s which a r e end B c e l l s  ( N o s s a l , 1976).  The a n t i g e n i s h e l d by the immunoglobulin r e c e p t o r  in  the c e l l membrane and i s p r o c e s s e d by i n t e r n a l i z a t i o n o r e n d o c y t o s i s . b i n d i n g o f a n t i g e n by B c e l l s i s e s s e n t i a l f o r the development o f o f a n t i b o d y ( B e n a c e r a f and Unanue, 1 9 7 9 ) . M, G , A , D, o r E .  The a n t i b o d y i s o f f i v e  The  production isotypes:  M, G , o r A a r e r e s p o n s i b l e f o r humoral and s e c r e t o r y  d e f e n s e w h i l e IgD i s p r e s e n t l y o n l y known as a membrane bound r e c e p t o r on many l y m p h o c y t e s , and IgE i s concerned w i t h t h e a l l e r g i c r e s p o n s e ( B e n a c e r a f and Unanue, 1 9 7 9 ) . 2.1.3.1  The S t r u c t u r e o f A n t i b o d i e s ( f i g u r e  2.1)  A n t i b o d i e s b e l o n g t o a c l a s s o f p r o t e i n s c a l l e d immunoglobulins.  The b a s i c u n i t o f s t r u c t u r e  two i d e n t i c a l  "light"  i s a complex o f f o u r  (low m o l e c u l a r w e i g h t ) c h a i n s and two  polypeptides, identical  " h e a v y " ( h i g h m o l e c u l a r w e i g h t ) c h a i n s l i n k e d t o g e t h e r by d i s u l p h i d e  6  L Choin Hypervoriable Regions  C3 H  Figure 2.1.  The IgG Antibody Molecule: a' Schematic Presentation of Structure (Benaceraf and Unanue, 1979)  7  bonds (Hood e t . a l . , 1 9 7 8 ) .  The f i v e c l a s s e s o f a n t i b o d i e s a r e c a l l e d  i s o t y p e s and t h e i r d i f f e r e n t s t r u c t u r e s a r e determined by t h e i r chains.  heavy  T h u s , IgG has gamma heavy c h a i n s , IgM has mu, IgA has a l p h a ,  IgD has d e l t a , and IgE has e p s i l o n heavy c h a i n s .  A l l i s o t y p e s may have  one o f two types o f l i g h t c h a i n , e i t h e r kappa o r  1 ambda.  The heavy  c h a i n s have t h r e e c o n s t a n t r e g i o n s and one v a r i a b l e r e g i o n ( a t the aminoterminal  end) w h i l e the l i g h t c h a i n s have one c o n s t a n t w i t h one v a r i a b l e  region.  The v a r i a b l e r e g i o n s a r e f u r t h e r composed o f framework  regions,  and h y p e r v a r i a b l e r e g i o n s w h i c h a r e the l e a s t homogenous r e g i o n s o f immunoglobulin  ( B e n e c e r a f and Unanue, 1 9 7 9 ) .  the  The v a r i a b l e r e g i o n s o f  the  heavy and l i g h t c h a i n s form a c l e f t which i s the s p e c i f i c b i n d i n g s i t e  of  the a n t i b o d y f o r an a n t i g e n ( S e a r h a r t e t a l _ . , 1 9 8 1 ) .  is  The b i n d i n g s i t e  p r e c i s e l y complementary t o the s t r u c t u r e o f the a n t i g e n and b i n d s to a n t i g e n by weak e l e c t r o s t a t i c a t t r a c t i o n ,  the  hydrogen b o n d i n g , and Van der  Waal f o r c e s ( B a c h , 1 9 7 8 ) . The s y n t h e s i s o f t h e s e immunoglobulins  i s c o n t r o l l e d by  gene c l u s t e r s (Hood e t a_K, 1 9 7 8 ) . For each heavy o r l i g h t c h a i n a d i v e r s e cluster of V (variable)  r e g i o n genes o f unknown number i s l i n k e d w i t h a  c l u s t e r of C (constant)  r e g i o n genes on one chromosome.  T h u s , heavy c h a i n  c l u s t e r s o f V and C r e g i o n s may be on one chromosome, a kappa C r e g i o n w i t h a c l u s t e r o f V r e g i o n s on a n o t h e r , and a V r e g i o n s on a n o t h e r .  lambda C r e g i o n w i t h a c l u s t e r  of  A s i n g l e V r e g i o n on the chromosome f o r the heavy  c h a i n can be a s s o c i a t e d w i t h two o r more C r e g i o n genes d u r i n g the d i f f e r e n t i a t i o n o f a n t i b o d y p r o d u c i n g c e l l s (Hood e t . a l . , 1978) r e s u l t i n g i n idiotypes  (i.e.  identical  v a r i a b l e r e g i o n s ) among d i f f e r e n t  identical  isotypes.  F u r t h e r work by Tonegawa e t a]_., (1978) found the p r e s e n c e o f J ( j o i n i n g )  8  l o c i on l i g h t c h a i n chromosomes, and both J and D ( d i v e r s i t y )  l o c i on heavy  c h a i n chromosomes. D i v e r s i t y o f a n t i b o d y p r o d u c t i o n t o deal w i t h the many p o s s i b l e a n t i g e n s i n the e n v i r o n m e n t , i n t h e o r y , r e s u l t s from two p o s s i b l e mechanisms (Hood e t a l _ . , ( 1 9 7 8 ) .  The f i r s t i s d i v e r s i t y w i t h i n the same  germ l i n e ( i . e . d i v e r s i t y o f V r e g i o n g e n e s ) . T h u s , a c o m b i n a t i o n from the s e l e c t i o n o f v a r i a b l e l i g h t c h a i n genes w i t h v a r i a b l e heavy c h a i n genes produces a m u l t i p l e o f them i n a n t i b o d y c l e f t s .  In c o m b i n a t i o n w i t h J and  D l o c i there i s a f u r t h e r m u l t i p l i c a t i o n of d i v e r s i t y (Gearhart et a l _ . , 1981). The second mechanism o f a n t i b o d y d i v e r s i t y c o u l d r e s u l t from s o m a t i c m u t a t i o n o r r e c o m b i n a t i o n which c o u l d o c c u r d u r i n g an i n d i v i d u a l ' s immune development. The consequence o f t h e s e mechanisms i s a v e r y d i v e r s e r e p e r t o i r e o f  antibody  s p e c i f i c i t i e s w h i c h , i n the p r e s e n c e o f a n t i g e n s t i m u l a t i o n , l e a d s t o a c o n t i n u o u s l y c i r c u l a t i n g a r r a y o f a n t i g e n s p e c i f i c lymphocytes ready to p r o liferate  under h e a v i e r a n t i g e n s t i m u l a t i o n .  The newborn i s i n e x p e r i e n c e d i n  the environment which i s c o n s t a n t l y p r e s e n t i n g d i v e r s e a n t i g e n s and c o n s e q u e n t l y has an undeveloped r e p e r t o i r e o f lymphocytes t o r e s p o n d . The a n t i b o d y c l a s s e s d i f f e r i n g r o s s f o r m a t i o n IgG i s a monomer o f two heavy and two l i g h t s c h a i n s o f  ( Table  immunoglobulin.  IgM i s a pentamer which i s h e l d t o g e t h e r by a j o i n i n g c h a i n w i t h d i s u l p h i d e bonds ( T o m a s i , 1 9 7 6 ) . disulphide  2.1)  (J)  IgM may a l s o be a s s o c i a t e d i n  o r n o n - c o v a l e n t bonds w i t h another p r o t e i n , the s e c r e t o r y component  ( B r a n d t z a e g & B a k l i e n , 1977) a t l e a s t i n human IgM. IgA may e x i s t as a monomer, o r as a dimer w i t h a J c h a i n as i n serum.  It  may a l s o e x i s t as s e c r e t o r y IgA ( S - I g A ) w h i c h i s a dimer  w i t h J c h a i n and s e c r e t o r y compoent ( S C ) .  The b i n d i n g o f SC i n IgM i s weaker  (more n o n - c o v a l e n t bonding) than i n S-IgA ( B r a n d t z a e g & B a k l i e n , 1 9 7 7 ) . IgD  Immunoglobulin  Light Chain Type  Heavy Chain Type  Other Components  Structure  10  and IgE b o t h e x i s t as monomers. Both J c h a i n and S e c r e t o r y Component a r e p o l y p e p t i d e s (Tomasi, 1976).  A c c o r d i n g t o B r a n d t z a e g & B a k l i e n (1977) J c h a i n i s  s y n t h e s i z e d i n the plasma c e l l w i t h immunoglobulin where i t the IgA o r IgM.  SC i s produced by s e r o u s t y p e e p i t h i l i a l  as a s p e c i f i c r e c e p t o r f o r the i m m u n o g l o b u l i n .  polymerizes  c e l l s and a c t s  C o v a l e n t and n o n - c o v a l e n t  i n t e r a c t i o n between SC and immunoglobulin a r e completed d u r i n g the passage o f the complex through the e p i t h i l i a l  c e l l s a n d , c o n j u g a t e d IgA ( o r  IgM)  w i t h S C , p l u s f r e e SC i s t r a n s p o r t e d i n t o the lumen by e x o c y t o s i s ( B e n a c e r a f and Unanue, 1 9 7 9 ) .  S i n c e S - I g A i s the predominate immunoglobulin i n a l l  body  f l u i d s o u t s i d e the v a s c u l a r system ( w i t h the e x c e p t i o n o f c o l o s t r u m which c o n t a i n s m o s t l y IgG)  ( P o r t e r , 1 9 7 6 ) , t h i s model p r o b a b l y a p p l i e s to  e x o s e c r e t i o n s o f s e c r e t o r y IgA. by g a s t r o - i n t e s t i n a l to f a c i l i t a t e epithilium 2.1.4  SC c o n j u g a t e d IgA i s r e s i s t a n t t o  enzymes (Tomasi and C a l v a n i c o , 1 9 6 8 ) .  all  proteolysis  SC i s a l s o thought  b i n d i n g o f the immunoglobulin t o the mucosa c o a t o f the  intestinal  (Porter et al_., 1972). Complement The term complement r e f e r s to a complex group o f enzymes  i n normal b l o o d serum (Mayer, 1 9 7 3 ) . o f 17 plasma p r o t e i n s  ( B e n a c e r a f and Unanue, 1979) w h i c h comprise a s i g n i f i c a n t  p o r t i o n o f the serum g l o b u l i n f r a c t i o n proteins f a l l  T h u s , the complement system c o n s i s t s  i n t o two f u n c t i o n a l  (Hood e t a j _ . , 1 9 7 8 ; M a y e r , 1 9 7 3 ) .  groups.  One group i s t h e c l a s s i c a l  These  com-  ponents which a r e s y m b o l i z e d w i t h a c a p i t a l C and a number, one t o n i n e .  The  o t h e r group i s t h e components o f t h e a l t e r n a t e pathway w h i c h a r e denoted w i t h a c a p i t a l l e t t e r and a r e B , D, and P ( p r o p e r d i n ) .  Many o f t h e s e p r o t e i n s  c l e a v e d d u r i n g complement r e a c t i o n s and c l e a v a g e fragments a r e s u f f i x e d  \  are  with  11  lower case l e t t e r s ,  f o r e x a m p l e , C3a and C 3 b , w i t h the s u f f i x b d e n o t i n g  the l a r g e r o f the two fragments ( B e n e c e r a f and Unanue, 1 9 7 9 ) . The f u n c t i o n s o f complement a r e s e v e r a l - f o l d .  Completion  o f the complement sequence on an a t t a c k e d c e l l l e a d s to c y t o l y s i s .  The  c l e a v a g e p r o d u c t o f C 3 , C3B, b i n d s to m i c r o o r g a n i s m c e l l s u r f a c e s p r o d u c i n g immune adherence which f a c i l i t a t e s Unanue, 1 9 7 9 ) .  p h a g o c y t o s i s (Mayer, 1973; B e n a c e r a f and  C3a and C5a c l e a v a g e fragments a r e a n a p h y l o t o x i n s which are  noted f o r c a u s i n g l e t h a l  bronchospasm i n g u i n e a p i g s and wheal and f l a r e  r e a c t i o n s i n human s k i n by d e g r a n u l a t i n g mast c e l l s ( B e n a c e r a f and Unanue, 1979).  A n a p h y l o t o x i n s a r e a c t i v e i n o t h e r mammals a l s o , c a u s i n g a c u t e  inflammation  (Hood e t a l _ . , 1 9 7 8 ) .  C5a and f r e e C 5 b - 6 - 7 complex a r e chemo-  t a c t i c f a c t o r s which a t t r a c t p o l y m o r p h o n u c l e a r l e u c o c y t e s (PMN), which a r e p h a g o c y t e s , to a s i t e o f complement a c t i v i t y  (Hood e t a l _ . , 1 9 7 8 ) .  The sequence o f the complement cascade i s most s i m p l y demonstrated i n f i g u r e 2 . 2 .  E s s e n t i a l l y , t h e r e i s an e f f e c t o r pathway (C5 to  C9) which " p u n c h e s " a h o l e i n the a f f e c t e d c e l l and can be a c t i v a t e d by e i t h e r the c l a s s i c a l sequence i n v o l v i n g C l , C 2 , C4 and c a l c i u m o r the sequence i n v o l v i n g B, D, P and magnesium. s p e c i f i c a n t i b o d y which must be e i t h e r  alternate  The c l a s s i c a l sequence r e q u i r e s  IgM o r IgG.  bound t o an a n t i g e n on a c e l l membrane w i l l  A s i n g l e m o l e c u l e o f IgM  i n i t i a t e the c l a s s i c a l sequence  whereas two a d j a c e n t IgG m o l e c u l e s a r e n e c e s s a r y .  Since antibody i s  scattered  o v e r the c e l l s u r f a c e q u i t e r a n d o m l y , the p r o b a b i l i t y o f two IgG m o l e c u l e s o c c u p y i n g a d j a c e n t s i t e s i s q u i t e s m a l l and t h e r e f o r e the f r e q u e n c y w i t h which IgG a c t i v a t e s the c l a s s i c a l sequence i s low (Mayer, 1 9 7 3 ) .  The a l t e r n a t e  pathway i s a n o n - s p e c i f i c mechanism o f immune d e f e n s e (Mayer, 1977) s i n c e doesn't require antibody f o r i n i t i a t i o n .  It  it  i s i m p o r t a n t i n defense a g a i n s t  12  endotoxin (alternative pathway)  antigen-antibody complex (classical pathway) activation  properdin factors B and D  physiological ^ functions  immune adherence and phagocytosis , CS C7  freeCSb.6,7 complex  Acute inflammation blood-vessel dilation transudation P M N chemotaxls phagccytosii lysosomal activation necrosis repair regeneration  CB OB  | holes in membrane (lysis) |  Figure  2.2  Activation of  Pathways and P h y s i o l o g i c a l  Complement  Components  Functions  (Hood e t a l _ . , 1978)  13 gram-negative b a c t e r i a t h a t i n h a b i t the gut. cell  Lipopolysaccharide  w a l l s o f these organisms ( e n d o t o x i n s ) combine d i r e c t l y w i t h the  f a c t o r , properdin  (Hood e t al_., 1978).  pathway ( H i l l  and  Porter,  1974).  the serum  There i s i n d i c a t i o n t h a t S-IgA w i l l  a l s o a c t with lysozyme to a c t i v a t e complement f i x a t i o n by  and  from  Both the c l a s s i c a l  the  alternate  a c t i v a t i o n sequence  the a l t e r n a t e pathway l e a d to cleavage o f C3 which i n i t i a t e s  the e f f e c t o r  sequence. 2.1.5  Antibody Reactions i n the Gut T a b l e 2.2  both s y s t e m i c a l l y and  Associated  l i s t s most o f the  Lymphoid T i s s u e  known a c t i v i t i e s o f a n t i b o d y  e x t e r n a l l y as " s e c r e t o r y a n t i b o d y " .  associated  lymphoid t i s s u e (GALT) there are e s s e n t i a l l y two  defense as  i n t e r p r e t e d by Tomasi  reactions within reactions  the  intestinal  c u l t u r e s as c h a l l e n g e  lumen and  the  second l i n e o f defense  and  concentrations  0.5,  0.05,  A.  being  i n h i b i t i o n of absorption to r e c e p t o r s  intestinal  segments and  first  live E.  Miler coli  p r o t e c t i v e e f f e c t s of  IgA were d i f f e r e n t , the minimum e f f e c t i v e andO.005 mg/ml r e s p e c t i v e l y f o r IgG, does not possess  o f b a c t e r i a or by b l o c k i n g cells.  The  demonstrated by S t e e l e e t al_. (1974).  organisms.  of binding  e f f i c a c y o f IgA was  M,  and  enterotoxin  of  to  enterotoxin  further  They found t h a t o f the  most e f f e c t i v e i n r e d u c i n g  i n f e c t e d with l i v e c h o l e r a  involves  The  t h a t the mechanisms o f a c t i o n might be due  on e p i t h e l i a l  g l o b u l i n s , S-IgA was  involves  by S-IgA (as copra a n t i b o d i e s ) .  M i l e r e t al_. (.1975) f u r t h e r s t a t e d t h a t IgA  n e u t r a l i z i n g a c t i v i t y and  l i n e o f defense  to s y s t e m i c immunity.  i n j e c t i o n s , found t h a t l o c a l IgM,  gut  l i n e s of antibody  first  l i g a t e d porcine  immunoglobulins IgG,  the  The  i n the t i s s u e s o f the GALT a l l i e d  (1975), using  Within  (1976).  l i n e o f defense i s mainly c a r r i e d out et aK  (GALT)  immuno-  mortality in rabbits  14  T a b l e 2.2  Mechanisms o f A n t i b o d y A n t i - b a c t e r i a l  Class of Antibody  IgG  Activity  Activity  Toxin n e u t r a l i z a t i o n Agglutination Opsonization B a c t e r i o l y s i s by complement f i x a t i o n I n h i b i t i o n of b a c t e r i a l adherence* 1  1  IgM  Toxin n e u t r a l i z a t i o n Agglutination* Opsonization B a c t e r i o l y s i s by complement 1  J  IgA  i fixation  Anti-toxin activity* Agglutination I n h i b i t i o n of bacterial m o t i l i t y Bacteriostasis I n h i b i t i o n of b a c t e r i a l adherence* Complement f i x i n g by the a l t e r n a t e pathway * B i n d i n g t o mucin o f m u c o s a * I n h i b i t i o n o f b a c t e r i a l enzymes I n h i b i t i o n o f f o r e i g n a n t i g e n uptake M  5  1.  B e n a c e r a f and Unanue, 1979  2.  T o m a s i , 1976  3.  Brandenburg and W i l s o n , 1974  4.  M c C l e l l a n d , 1979  5.  P o r t e r , e t a l _ . , 1976  J  15  The second l i n e o f d e f e n s e , o r s y s t e m i c immunity, depends l a r g e l y on IgG and IgM.  The a c t i v i t i e s o f IgG and IgM a r e q u i t e  different.  Due to i t s pentameric f o r m , IgM has more a c t i v e a n t i b o d y b i n d i n g s i t e s than IgG ( B a c h , 1 9 7 8 ) .  T h u s , the a c t i v i t y o f IgM i s c o n s i d e r e d to be  greater i n antibody r e a c t i o n s .  Rowley and T u r n e r (1966) found the 8 IgM  m o l e c u l e s / b a c t e r i u m were n e c e s s a r y as o p s o n i n s whereas 2200 IgG m o l e c u l e s / b a c t e r i u m were n e c e s s a r y .  Brandenbourg and W i l s o n (1974) s t a t e d t h a t IgM  was 500 to 1000 times more e f f e c t i v e as an o p s o n i n than IgG. s t a t e d t h a t IgM was much more e f f e c t i v e i n complement f i x a t i o n 2.1.4).  They a l s o (See S e c t i o n  S t e e l e e t a l _ . , (1974) developed d a t a s u p p o r t i n g the g r e a t e r  o f IgM u s i n g r a b b i t Ig a g a i n s t V. c h o l e r a e .  activity  P o r t e r e t a l ^ , (1977) say t h a t  the dominant immunoglobulins found i n the lamina p r o p r i a a r e IgM and IgA. S i n c e IgM may form o n l y a s m a l l p a r t o f the s e c r e t e d I g , i t may form a s t r o n g second l i n e o f d e f e n s e i n t i s s u e s b e h i n d the e p i t h i l i u m ( A l l e n and P o r t e r , 1973) where i t  can c a r r y o u t complement f i x a t i o n , o p s o n i z a t i o n a g g l u t i n a t i o n ,  and t o x i n n e u t r a l i z a t i o n a g a i n s t p a t h o g e n i c i n v a d e r s .  16  2.2  P r e n a t a l Development o f the P o r c i n e Immune System (see T a b l e 2 . 3 ) Working w i t h the f e t a l  lamb and f e t a l  mouse i t was found t h a t  development o f competence i n the mammalian f e t u s o c c u r s i n a c o n t r o l l e d , step-wise fashion.  " A h i e r a r c h y o f a n t i g e n s e x i s t s t o which the  fetus  d e v e l o p s competence a t d i f f e r e n t s t a g e s o f g e s t a t i o n " ( S i l v e r s t e i n , 1 9 7 7 ) . The immunologic competence m a t u r a t i o n ment.  The f e t u s b e f o r e h a v i n g o r g a n i z e d lymphoid t i s s u e i s a b l e to respond  t o some a n t i g e n s presumably u t i l i z i n g Once i t  i s independent o f lymphoid d e v e l o p -  lymphoid c e l l s i n the f e t a l  liver.  i s competent to a c e r t a i n a n t i g e n , the f e t u s i s a b l e t o produce  comparable a n t i b o d y t i t r e s t o an a d u l t ,  and forms them i n the usual sequence  o f immunoglobulin c l a s s e s (IgM f o l l o w e d by IgG) ( S i l v e r s t e i n , 1 9 7 7 ) . e v e r , i n c o n t r a d i c t i o n , t h e r e may be some r e s t r i c t i o n s  to f e t a l  How-  response.  The l e v e l o f a n t i g e n needed f o r s t i m u l a t i o n may be h i g h e r ( S t e r z l , 1 9 6 3 ) , o r t h e r e may be fewer stem c e l l s , o r t h e r e may be c l o n a l r e s t r i c t i o n initial  response (Klinman and P r e s s ,  1975).  in  the  17  Prenatal  T a b l e 2.3  Development o f t h e P o r c i n e Immune System  Event  G e s t a t i o n a l Time o f Occurrence Day  28  Day 32 Day 38 Day 40 Day 51  Lymphoid c e l l s a r e d e t e c t e d i n t h e r e g i o n o f t h e thymus' The lymph nodes begin forming w i t h o u t germinal c e n t r e s ( u n l e s s t h e animal i s i n f e c t e d / , Lymphoid c e l l s a r e d e t e c t e d i n the l i v e r and blood Components o f t h e complement system a r e p r e s e n t * Number o f lymphocytes g r a d u a l l y begin t o i n c r e a s e i n the s p l e e n Less than 1% o f the lymphocytes have s u r f a c e immunoglobulin^ H i s t o l o g i c a l l y , t h e thymus i s i d e n t i c a l t o development a t b i r t h ' In t h e lamina p r o p r i a o f t h e t e r m i n a l ileum lymphocytes occur i n f o l l i c u l a r a g g r e g a t i o n s ' Approximately 10% o f blood lymphocytes have s u r f a c e immunoglobulin i n d i c a t i n g development o f immunocompetence* A more g e n e r a l i z e d f o l l i c u l a r lymphoid s t r u c t u r e i s d e v e l o p i n g with l a r g e r p o p u l a t i o n s o f lymphocytes. Immune responses can be shown a g a i n s t several antigens: f o r m a l i z e d Salmonella* , sheep red blood c e l l s * and p h a g e . Transplantation immunity, to a l l o g e n e i c c e l l s was induced a f t e r 80 days ; i f i n j e c t e d a t 60 days, a l l o g e n e i c c e l l s induce t o l e r a n c e to s k i n g r a f t s . Peyer's patches a r e p r e s e n t ' 1  Before 65 days Day 77  A f t e r 70 - 80 days  A f t e r 80 days  6  7  At  birth  1.  Kruml e t a l _ . , 1970  2.  Pestana  3.  Day e t a l _ . , 1969  4.  B i n n s , 1973  5.  Binns  6.  T l a s k a l o v a e t a l _ . , 1970  7.  B i n n s , 1967  e t a l _ . , 1965  and Symons, 1973  18  2.3  P o s t n a t a l Development o f the P o r c i n e Immune System In g e r m - f r e e neonatal p i g l e t s , no immunoglobulin i s  found  w i t h the e x c e p t i o n o f a s m a l l " h a l f m o l e c u l e " o f IgG type which has been shown t o c o n s i s t o f one heavy and one l i g h t c h a i n and i s not r e s p o n s i v e (Prokesova e t a l _ . , 1 9 7 0 ) .  antigen  T h i s fragment has been t h e o r i z e d as  a r e l e a s e d , membrane-associated immune r e c e p t o r m o l e c u l e from lymphocytes ( P o r t e r , 1979).  Due to an e p i t h i l i o c h o r i a l  p l a c e n t a , the  pig fetus  prevented from r e c e i v i n g a n t i b o d y from the dam's c i r c u l a t i o n . for this  is  The reason  i s u n c l e a r , b e c a u s e , a l t h o u g h i n the e a r l y embryonic s t a g e s as  many as s i x h i s t o l o g i c a l l y d i s t i n c t  l a y e r s s e p a r a t e the two b l o o d s t r e a m s ,  i n l a t e r pregnancy the embryonic c a p i l l a r i e s d e v e l o p more i n p o s i t i o n s and invade the embryonic t r o p h o b l a s t bloods a r e i n c l o s e p r o x i m i t y the c i r c u l a t o r y  so t h a t maternal  (Marrable, 1971).  s u p p l y , no maternal a n t i b o d i e s  sub-epithilial  Whatever the s i t u a t i o n ( o r immeasurable  pass (Kim e t a l _ . , 1 9 6 7 ) . The p l a c e n t a i s a l s o thought to b l o c k stimulation  and f e t a l of  quantities) antigen  (Prokesova e t a l _ . , 1 9 7 0 ) . Immunization o f a newborn p i g l e t w i t h a l a r g e dose o f  results in a relatively  r a p i d onset of antibody formation  A n t i b o d i e s are produced w i t h i n 36 hours as IgM, and a f t e r  antigen  i n the b l o o d . 6 days both IgM  and IgG which were a n t i g e n r e s p o n s i v e a r e found ( P r o k e s o v a e t a l _ . , 1 9 7 0 ) . However, i f  c e r t a i n a n t i g e n s ( e . g . Hog C h o l e r a V i r u s ) a r e u s e d ,  i n neonates i n d u c e s t o l e r a n c e T h i s neonatal  to t h a t a n t i g e n .  injection  (Weide e t aj_., 1 9 6 2 ) .  i n d u c t i o n o f t o l e r a n c e to c e r t a i n a n t i g e n s i m p l i e s an  i m m a t u r i t y o f development and i s commonly demonstrated i n mice ( B e n e c e r a f and Unanue, 1 9 7 9 ) . After birth,  lymphocytes a r e a n t i g e n i c a l l y s t i m u l a t e d a t  the  19  P e y e r ' s patches a n d / o r the m e s e n t e r i c lymph nodes t o precommitment  for  IgA p r o d u c t i o n ; they then e n t e r the c i r c u l a t i o n and home m a i n l y to  the  l a m i n a p r o p r i a o f the s m a l l i n t e s t i n e .  T h u s , a response o f the  s e c r e t o r y immune system r e q u i r e s a n t i g e n i c s t i m u l a t i o n .  intestinal  In the duodenum,  Brown and Bourne (1976) found c o n s i d e r a b l e numbers o f c e l l s s t a i n i n g each o f the t h r e e c l a s s e s o f immnuglobulin a f t e r  the f i r s t week.  for  The  presence o f IgM c e l l s was g r e a t e r than IgA c e l l s f o r the f i r s t 3 w e e k s ; IgA exceeded IgM c e l l s a f t e r 3 weeks d u r i n g which t i m e IgG c e l l s were p r e s e n t i n c o n s i d e r a b l e but s m a l l e r numbers.  A f t e r about 1 month, the  plasma c e l l p o p u l a t i o n o f the ducdenum was l i k e t h a t o f an a d u l t . Humoral immunity a l s o begins w i t h the presence o f s y n t h e s i z e d IgM f i r s t d u r i n g the end o f the f i r s t week; 7-12  days;  IgG i s found i n the serum a f t e r  IgA i s found i n the serum a f t e r 14 days (Bourne and C u r t i s ,  1973), The immune mechanism o f an a d u l t can be c o n t r a s t e d w i t h t h a t of a neonate.  The a d u l t has been p r i m e d , d u r i n g i t s a n t i g e n e x p e r i e n c e ,  t o a g r e a t d i v e r s i t y o f a n t i g e n s from b a c t e r i a l f l o r a , and t h i s response may be c r o s s - r e a c t i v e t o an even l a r g e r a r r a y o f i n v a d e r s .  Thus, a  response which appears p r i m a r y i n a d u l t s may r e a l l y be a secondary and more r a p i d l y o c c u r r i n g r e s p o n s e , whereas i n the young o r g e r m - f r e e animal a p r i m a r y response i s t r u l y p r i m a r y ;  (Solomon, 1 9 7 1 ) .  It  i s p u z z l i n g why a  p i g l e t which i s immunocompetent a t b i r t h s h o u l d be so s u s c e p t i b l e to p a r t i c u l a r l y when d e p r i v e d o f maternal a n t i b o d y .  But t h i s may be answered  t h a t because o f a n t i g e n i c v i r g i n i t y , t h e r e may be a r e a s o n a b l e d e l a y response.  E s s e n t i a l l y a r a c e o c c u r s between the m u l t i p l i c a t i o n  s t i m u l a t e d c e l l s and pathogens (Solomon, 1 9 7 1 ) .  infection  of  in  antigen  20  21  The g e n e r a l development o f the immune system a f t e r b i r t h a c o n t i n u o u s m a t u r a t i o n due t o s t i m u l a t i o n by n a t u r a l  antigens.  is  T h i s may  be observed i n the r a p i d enlargement o f lymphoid organs such as the s p l e e n and the s l o w e r development o f lymph nodes w i t h age (Solomon, 1 9 7 1 ) . structures  do not d e v e l o p n e a r l y as f a s t i n g e r m - f r e e a n i m a l s .  alimentary t r a c t of germ-free pigs there i s v i r t u a l l y lymphoid t i s s u e s by 31 days (Kenworthy,  In  These the  no development  of  1970).  C o n t r a s t i n g r e s u l t s have been found w i t h r e g a r d t o the o f c o l o s t r u m a n t i b o d y i n the newborn p i g . trials  Segre and Myers (1964)  found t h a t p i g l e t s seemed to respond b e t t e r  to  complexes where the a n t i b o d y i s s u p p l i e d by c o l o s t r u m .  in  natural  their  antigen-antibody A d u l t p i g s respond  j u s t as w e l l t o a n t i g e n a l o n e w h i c h , a c c o r d i n g t o t h e s e w o r k e r s , i s sumably because t h e r e i s s u f f i c i e n t  effect  antibody present i n  pre-  adults.  However, S t e r z l , e t a l _ . , (1965) found t h a t c o l o s t r u m tended to i n h i b i t active production of antibody.  L a t e r r e s u l t s tend not t o r e s o l v e  c o n t r a d i c t i o n e x c e p t t h a t low l e v e l s o f a n t i b o d y w i l l  this  sometimes enhance an  immunological response whereas h i g h l e v e l s o f a n t i b o d y w i l l response (Solomon, 1 9 7 0 ) .  the  cause a poor  The l a t e r case may be understood e i t h e r to be  a case o f removal o f a n t i g e n i c s t i m u l a t i o n 1967) o r a case o f n e g a t i v e f e e d b a c k .  by the a n t i b o d y  (Dixon e t a l . ,  Low l e v e l s o f a n t i b o d y may  facilitate  p h a g o c y t o s i s by macrophages and enhance a n t i g e n p r e s e n t a t i o n to T - h e l p e r cells  (Kim e t a l _ . , 1 9 6 6 ) . Sera from p r e - c o l o s t r a l , n e o n a t a l , g e r m - f r e e p i g l e t s  bactericidal  f o r rough s t r a i n s o f E . c o l i , and t h i s a c t i v i t y  is  can be  c o r r e l a t e d w i t h the presence o f complement ( S t e r z l e t a l _ . , 1 9 6 4 ) .  This  i s a mechanism which can f u n c t i o n n o n - s p e c i f i c a l l y a g a i n s t gram n e g a t i v e  22  b a c t e r i a w i t h o u t the presence o f a n t i b o d y and c o u l d be e f f e c t i v e any gut f l o r a which become i n v a s i v e .  against  23 2.4  The " R u n t " Phenomenon As b i r t h w e i g h t  decreases, mortality  increases (Carroll  e t a J L , 1962; S h a r p e , 1966; Fahmy and B e r n a r d , 1 9 7 1 ) .  Smaller pigs  o f t e n r e q u i r e manual a s s i s t a n c e to s u c k l e and a d d i t i o n a l warmth survive.  to  F a i l u r e t o s u c k l e can l e a d to hypoglycaemia and death  (Newland e t a l ^ . , 1 9 5 2 ) ; l a c k o f warmth can l e a d t o hypothermia and death. E x c e p t i o n a l l y s m a l l p i g s a t b i r t h a r e termed " r u n t s " a r e d i s t i n g u i s h e d from normal p i g s by both t h e i r d i s t i n c t i v e physical characteristics. r u n t s as b e i n g the l i g h t e s t  l i g h t w e i g h t and  Cooper e t al_.» (1970)  5% o f the t o t a l  defined  population at b i r t h .  and Rowel 1 (1969) took a r u n t to have a p r e n a t a l w e i g h t o f o f the average f o r i t s u t e r i n e h o r n .  and  Perry  two-thirds  P h y s i c a l l y , r u n t s are s m a l l ,  thin,  and have a d i s p r o p o r t i o n a t e l y l a r g e r and more domed head than normal progeny. The p h y s i c a l c h a r a c t e r i s t i c s o f a r u n t a r e the r e s u l t intra-uterine  growth r e t a r d a t i o n w h i c h i s not the r e s u l t o f f e t a l  of  anomoly  o r maternal i l l n e s s (Cooper e t a l _ . , 1 9 7 8 ) . The r u n t i n g phenomenon may be a r e s u l t of i n t r i n s i c function  fetal  growth f a c t o r s o r be secondary to  (Cooper e t a l _ . , 1978) but the cause i s n o t c l e a r .  placental  When f i v e  or  fewer f e t i are i n each horn o f the u t e r u s , the p o s i t i o n o f the embryo has no e f f e c t on s i z e .  B u t , as the number i n c r e a s e s , those a t e i t h e r end  tend to have an i n c r e a s i n g advantage o v e r those i n the m i d d l e o f the h o r n , and t h o s e a t the o v a r i a n end have a g r e a t e r advantage t h a n t h o s e a t c e r v i c a l end ( P e r r y and Rowel 1 , 1 9 6 9 ) .  the  M a r r a b l e (1971) suggested t h a t even  w i t h s m a l l l i t t e r s i z e s , the p o s i t i o n a l e f f e c t w i l l  be o p e r a t i v e l a t e r  in  24  pregnancy.  Waldorf  e t al_.,  (1957) suggested  t h a t the u t e r i n e a r t e r i e s  p r o v i d e d h i g h e r blood p r e s s u r e a t t e r m i n a l s i t e s b u t , although t h i s may be r e l e v a n t i n o t h e r m u l t i p a r o u s mammals, the p o r c i n e v a s c u l a r system i s such t h a t supply t o the c e r v i x and u t e r i n e body i s augmented by a branch from the u r o g e n i t a l a r t e r y Several runting. of  ( M a r r a b l e , 1971).  s t u d i e s have been done about p r e n a t a l appearance o f  Pomeroy (1960) found s i g n i f i c a n t r u n t i n g appearance a t 74 days  g e s t a t i o n but not a t 51 days.  P e r r y and Rowel 1  l e s s than t w o - t h i r d s t h e weight f o r the average  (1969) found  feti of  o f t h e u t e r i n e horn a t 31  to  49 days o f g e s t a t i o n and i d e n t i f i e d these as r u n t s appearing(y>Cooper  et  al_.,  of  gestation.  (1978) found  runts a t g e s t a t i o n a l  O b v i o u s l y these data do n o t p i n - p o i n t a c o n c l u s i v e stage o f  g e s t a t i o n a t which f e t a l cent o f f e t a l  ages o f 44, 53, 56 and 75 days  growth r e t a r d a t i o n o c c u r s .  growth (by weight) o c c u r s a f t e r day 40 o f g e s t a t i o n ( M a r r a b l e ,  1971), the o c c u r r e n c e o f r u n t i n g t h i s e a r l y suggests r e t a r d a t i o n may be determined throughout  However, s i n c e 99 per  fetal  that intra-uterine  b e f o r e i t becomes r e c o g n i z a b l e and may o c c u r  development i n some c a s e s . Widdowson (1971) compared the development o f organs i n the  r u n t with t h a t o f a f e t u s taken a t an equal mate o f normal s i z e .  s i z e and with t h a t o f a  Two o u t s t a n d i n g d i f f e r e n c e s were noted:  litter-  firstly,  muscle development, as measured by q u a d r i c e p s s i z e was s i g n i f i c a n t l y in  the r u n t than i n e i t h e r the f e t u s o f equal weight o r the normal  less  litter-  mate; s e c o n d l y , the l i v e r s o f the f e t u s and r u n t were comparable i n s i z e yet  v e r y much s m a l l e r than the l i v e r o f the normal l i t t e r m a t e with t h e  added c h a r a c t e r i s t i c o f a very low carbohydrate  c o n t e n t i n the r u n t . Heart,  s p l e e n and stomach o f the r u n t were i n t e r m e d i a t e i n weight between  those  25  o f the f e t u s and normal l i t t e r m a t e .  The b r a i n o f the r u n t was n e a r e r  t o normal w e i g h t than any o t h e r p a r t o f t h e body.  G e n e r a l l y , Widdowson  (1971) found t h a t t h e d e c r e a s e i n organ s i z e o f the r u n t was due t o  both  h y p o p l a s i a ( d e c r e a s e d c e l l s i z e ) and hypotrophy ( d e c r e a s e d c e l l number). Widdowson (1971) went on t o compare t h e growths o f a r u n t and a normal littermate  f o r t h r e e y e a r s and found t h a t the r u n t was 60 k g . l i g h t e r  t h e end o f t h i s t e r m .  at  S i n c e t h e r e were no r e s t r i c t i o n s i n d i e t o r as a  r e s u l t o f e n v i r o n m e n t a l e f f e c t s a f t e r w e a n i n g , i t may i n d i c a t e t h a t u t e r i n e growth r e t a r d a t i o n may p r o v i d e a permanent s e t - b a c k .  intra-  26 2.5  Mechanisms o f A c t i o n o f B a c t e r i a i n the  Intestine  W i t h i n the i n t e s t i n e t h e r e a r e t h r e e major ways t h a t b a c t e r i a may a s s o c i a t e w i t h the i n t e s t i n a l  mucosa to produce d i s e a s e .  Firstly,  they  can a t t a c h to the mucosa w i t h o u t p e n e t r a t i o n and i n d u c e d i s e a s e by m u l t i -  3 p l y i n g and p r o d u c i n g e x o t o x i n  .  This occurs i n E. c o l i e n t e r i t i s  s m a l l i n t e s t i n e and i s caused by e n t e r o t o x i n p r o d u c i n g E . c o l i . b a c t e r i a can a t t a c h t o and p e n e t r a t e the mucosa but not the t i s s u e s and induce d i s e a s e by damaging e p i t h i l i a l exotoxin.  T h i s can o c c u r i n E . c o l i e n t e r i t i s  i s caused by i n v a s i v e s t r a i n s o f E . c o l i .  of  the  Secondly,  subepithilial  c e l l s and a l s o produce  o f the l a r g e i n t e s t i n e and  T h i r d l y , b a c t e r i a can a t t a c h  to,  and p e n e t r a t e the mucosa t o reach the s u b e p i t h e l i a l t i s s u e s , m u l t i p l y  in  the submucosa, and spread s y s t e m a t i c a l l y a l s o growing i n t r a c e l l u l a r ^  in  phagocytes.  T h i s mode o f a c t i o n o c c u r s w i t h S a l m o n e l l a e n t e r i t i s  by S . t y p h i .  ( M c C l e l l a n d , 1979). A major phenomenon i n v o l v e d i n b a c t e r i a l  thelial  surfaces i s b a c t e r i a l adherence.  invasion of  caused  epi-  S i n c e p e r i s t a l s i s and f l u s h i n g  w i t h s e c r e t i o n s tends to remove b a c t e r i a and m a i n t a i n a c o n t i n u o u s l y l e v e l o f growth and p r e v e n t i n v a d e r s from p r o l i f e r a t i n g ,  attachment to  gut e p i t h e l i u m by adherence i s a major mechanism a f f e c t i n g a pathogen to p r o l i f e r a t e .  the of  with  The most s t u d i e d i s the K88 a n t i g e n which  has n o n - f l a g e l l a r f i l a m e n t o u s s u r f a c e p i l l i plasmid.  the a b i l i t y  B e s t known i n t h i s c o n n e c t i o n i s E . c o l i  i t s varying adhesion f i m b r i a e .  lower  (Smith and L i n g g o o d , 1 9 7 1 ) .  c a r r i e d on the genome o f a  Other adherence f a c t o r s o f E . c o l i  the n e o n a t a l p o r c i n e i n t e s t i n e a r e the a n t i g e n s K 9 9 , s t r a i n 987 t y p e , and type 1 common p i l l i intestinal  o f which each has a d i f f e r e n t  r e c e p t o r s i t e on the  e p i t h e l i u m (Dupond and P i c k e r i n g , 1 9 8 0 ) .  A l l of these surface  in  27 s t r u c t u r e s a r e a n t i g e n i c and e l i c i t  a n t i b o d y responses where the  antibody  a c t s as an a n t i - a d h e r e n c e f a c t o r p o s s i b l y by masking the adherence s i t e o f the b a c t e r i u m . site for i t  In r e f e r e n c e t o the K88 a n t i g e n , the p o r c i n e  receptor  i s c o n t r o l l e d by a dominant gene and t h e r e f o r e a n i m a l s which are  double r e c e s s i v e a r e immune to K88 s t r a i n s o f b a c t e r i a u n l e s s o t h e r are p r e s e n t d e t e r m i n i n g v i r u l e n c e .  (Rutter,  The mechanism o f e n t e r o t o x i n s two e n t e r o t o x i n s genic f o r swine:  1975; Rutter et a l _ . , 1976). i s not f u l l y u n d e r s t o o d .  have been shown t o be produced by s t r a i n s o f E . c o l i one i s a n t i g e n i c and heat l a b i l e  (LT) and the o t h e r  n o n - a n t i g e n i c and heat s t a b l e (ST) (Dupont and P i c k e r i n g 1 9 8 0 ) . are transmitted E. c o l i .  It  factors  However pathois  Both t o x i n s  by a p l a s m i d and both may be produced by the same s t r a i n  of  has been suggested t h a t the n o n - a n t i g e n i c ST was i m p o r t a n t i n  the d i a r r h e a o f swine ( G y l e s ,  1971).  28 2.6  Diarrhea i n P i g l e t s In  are  a normal, h e a l t h y i n t e s t i n a l mucosa, s a l t s and water  absorbed by an energy r e q u i r i n g mechanism.  The d r i v i n g  water a b s o r p t i o n i s an a c t i v e t r a n s p o r t o f e l e c t r o l y t e s , sodium and c h l o r i n e .  the small  particularly  Acute e n t e r i t i s , w h i c h causes d i a r r h e a i n newborn  animals^produced watery s t o o l s from f e c a l in  force of  intestine  fluid  primarily  (Tennant and Hornbuckle, 1980).  originating  The r a p i d de-  h y d r a t i o n causes hemoconcentration and a l o n g w i t h the movement o f i o n s , l e a d s t o m e t a b o l i c a c i d o s i s caused by r e n a l  f a i l u r e t o e x c r e t e hydrogen  i o n s and by i n c r e a s e d p r o d u c t i o n o f o r g a n i c a c i d s r e s u l t i n g from decreased t i s s u e oxygenation.  Hyperkalemia  (hiigh  potassium) a l s o r e s u l t s as does  hypoglycemia due t o decreased g l u c o n e o g e n e s i s and i n c r e a s e d a n a e r o b i c glycolysis  (Tennant and Hornbuckle, In  the  toxin  1980).  the s p e c i f i c case o f the e n t e r o t o x i c mechanism o f E. c o l i ,  (LT o n l y ) a c t s by b i n d i n g t o r e c e p t o r s on the mucosal  cell  membranes t o a c t i v a t e adenyl c y c l a s e which c o n v e r t s ATP to c y c l i c  AMP.  The cAMP a c t s as a second messenger t o i n f l u e n c e p e r m e a b i l i t y o f the membrane.  The net r e s u l t i s t h a t sodium a b s o r p t i o n i s b l o c k e d and  chlorine i s secreted. it  The c h l o r i n e i o n p u l l s water and c a t i o n s w i t h  i n t o the gut lumen to m a i n t a i n osmotic e q u i l i b r i u m .  cause o f f l u i d toxin  loss  (Dupont and P i c k e r i n g , 1980).  T h i s i s the  E. c o l i  heat s t a b l e  (ST) does not a c t i v a t e adenyl c y c l a s e however, as has been d i s c o v e r e d  r e c e n t l y , i n mice and r a b b i t s , i t s a c t i o n may be mediated  through the  b u i l d - u p o f guanyl c y c l a s e which produces cGMP (Hughes e t a l _ . , In hydrogen  1978).  the case o f S a l m o n e l l a i n f e c t i o n , s i m i l a r d e h y d r a t i o n and  i o n and e l e c t r o l y t e d i s t u r b a n c e s a r e the r e s u l t .  Salmonella  29  i s an i n v a s i v e organism and p e n e t r a t e s the mucosa and p r o l i f e r a t e s gut a s s o c i a t e d lymphoid t i s s u e (Dupont and P i c k e r i n g , 1 9 8 0 ) . can o c c u r t h r o u g h o u t the i n t e s t i n e a l t h o u g h i t gut mucosa more r e a d i l y .  U s i n g the r a t ,  d i a r r h e a i n c r e a s e d e s p e c i a l l y the i l e a l c h l o r i n e and p o t a s s i u m .  u s u a l l y invades the  Powell e t a l _ . , (1971)  They found an i n c r e a s e d h y d r o s t a t i c  i n c r e a s e d membrane  the  effect lower  showed  s e c r e t i o n o f w a t e r , sodium and  the lamina p r o p r i a , perhaps caused by venous o r l y m p h a t i c with resultant  Its  in  permeability.  pressure in  obstruction,  30 2.7  Non-Specific Gastro-intestinal  Immune Mechanisms  There i s a s e r i e s o f mechanisms which o p e r a t e i n defense a g a i n s t p a t h o g e n i c b a c t e r i a and i n some c a s e s , v i r u s e s and p a r a s i t e s . 2.7.1  The G a s t r i c Trap A g a s t r i c t r a p i s p r o v i d e d by the HCl which i s  and i s h i g h l y e f f e c t i v e  a g a i n s t almost a l l  g a s t r i c mucosa i s not f u n c t i o n a l ,  bacteria.  the if  b a c t e r i a are not reached by  the a c i d i t y o f the stomach, b a c t e r i a may pass t h i s i n the g a s t r o - i n t e s t i n a l  However, i f  a s , p o s s i b l y , i n the n e o n a t e , o r  the c h a l l e n g e dose i s l a r g e enough, o r i f  later  anti-bacterial  t r a p to  proliferate  t r a c t ( G i a n n e l l a et al_., 1971).  In n e o n a t e s , the work on g a s t r i c a c i d s e c r e t i o n seems q u i t e i n c o m p l e t e and c o n t r a d i c t o r y . i n a c l e a n environment  C r a n w e l l e t a l _ . , (1968) found t h a t  piglets  had a c i d s e c r e t i o n a t one week o f a g e , w h i l e  raised in a conventional  those  environment d i d n ' t s e c r e t e u n t i l 30 days o f a g e .  L a t e r , C r a n w e l l and T i t c h e n (1974) d i s c o v e r e d t h a t s e c r e t i o n c o u l d begin from 2 days o f age u s i n g a s u r g i c a l l y s e p a r a t e d pouch from the stomach and t h a t the s e c r e t i o n was s i g n i f i c a n t .  Hill  (1970) s t a t e d t h a t a c i d  s e c r e t i o n was v e r y minimal d u r i n g the f i r s t 2 weeks.  Jones (1972)  to work which s t a t e d t h a t HCl s e c r e t i o n does not begin u n t i l age o f m i l k f e d o r 14 days i f  given c e r e a l s .  d i s c r e p a n c i e s i s t h a t the p i g l e t w i t h i n a few days o f b i r t h , control  i t s development  2.7.2  Intestinal  20 days o f  The l i k e l y e x p l a n a t i o n  has a competent g a s t r i c mucosa a t  but e n v i r o n m e n t a l  ( C r a n w e l l and T i t c h e n ,  referred  or n u t r i t i o n a l  of  least  factors  1974).  Motility  The r a t e o f passage o f chyme w i l l determine t o a l a r g e whether l o c a l p r o p a g a t i o n w i l l o c c u r .  extent  There i s e v i d e n c e t h a t the t i m e o f  31 c o n t a c t between the e p i t h i l i a l  l i n i n g o f the gut and an i n v a s i v e pathogen  such as a S a l m o n e l l a s t r a i n o f b a c t e r i a determines the development disease ( S p r i n z , 1969).  It  has been shown by the use o f a g a n g l i o n  b l o c k i n g drug which slowed the r a t e o f p e r i s t a l s i s i n r a t s t h a t was a s u b s t a n t i a l intestine.  of  there  i n c r e a s e i n the number o f c o l i f o r m s i n the s m a l l  (Dixon and P a u l l e y , 1 9 6 3 ) .  Diarrhea i s associated with  decreased m o t i l i t y ( C h r i s t i a n s e n e t a l . , 1972) and gut s t a s i s 1975; White e t . a l . , 1972; K o h l e r , 1 9 7 2 ) .  (Rutter,  Related to i n t e s t i n a l  motility  i s the l e v e l o f s e c r e t i o n o f l a r g e amounts o f s t e r i l e f l u i d by the duodenum which washes o u t b a c t e r i a ( N i e l s o n e_t aj_-, 1 9 6 8 ) . 2.7.3  Intestinal  Microflora  In the d e v e l o p i n g p i g l e t activity fully  raised conventionally, while  gastric  i s l o w , b a c t e r i a a r e i n g e s t e d from the environment and s u c c e s s -  adapted s t r a i n s p r o l i f e r a t e .  P r o b a b l y , the e s t a b l i s h m e n t o f a  h e a l t h y and n a t u r a l m i c r o f l o r a o c c u r s here and e v o l v e s as the d i e t changes from m i l k to s o l i d f o o d .  In a h e a l t h y young p i g the e c o l o g y o f the  gut  m a i n t a i n s a homeostasis which i s f u r t h e r ensconced i n a more mature a n i m a l . In the n u r s i n g p i g l e t l a c t o b a c i l l i in i t s a c i d i t y  inhibits  create antibacterial volatile  proliferate  other b a c t e r i a .  p r o d u c i n g l a c t i c a c i d which  L a t e r , the r e s i d e n t  bacteria  c a t a b o l i t e s i n c l u d i n g l a c t i c a c i d and s h o r t  f a t t y a c i d s t o lower the pH.  In a d d i t i o n , the r e s i d e n t  dominate the demand f o r space and n u t r i e n t s  flora  to p r e v e n t o t h e r forms  g a i n i n g a c c e s s t o grow ( F r e t e r and Abrams, 1972; F r e t e r , 1 9 7 4 ) . w i t h c o n t i n u o u s f l o w c u l t u r e s , Ozawa and F r e t e r (1964) found t h a t s t a i n s used n e a r l y a l l energy s o u r c e s and any i n v a d e r s t r a i n proliferate  chain  from  Working resident  couldn't  u n l e s s a s o u r c e not used by the r e s i d e n t s was s u p p l i e d .  32  A n o t h e r f a c t o r o f the environment o f the lumen i s t h a t i t  has a low redox  p o t e n t i a l which a l l o w s o n l y c e r t a i n s t r a i n s o f b a c t e r i a t o (McClelland, 1979).  survive  A f u r t h e r f a c t o r i n f l u e n c i n g b a c t e r i a l ecology i n  t h e gut i s t h a t some b a c t e r i a can produce s p e c i f i c a n t i m i c r o b i a l s  of  l i m i t e d spectrum which appear t o i n f l u e n c e the a b i l i t y o f a p a r t i c u l a r s t r a i n t o s u r v i v e (Branche e t a K , 1 9 6 3 ) . a g a i n s t an i n f e c t i o n  In t r e a t i n g w i t h  antibiotics  ( e . g . S a l m o n e l l a ) the magnitude o f the c h a l l e n g e  dose may be reduced and the i n f e c t i o n may be p r o l o n g e d by r e d u c i n g the total  intestinal  f l o r a and a l l o w i n g the i n f e c t i v e s t r a i n t o  ( A s e r k o f f and B e n n e t t , 1 9 6 9 ) .  proliferate  The s t a b i l i t y o f the m i c r o f l o r a s u g g e s t s  t h a t immunity i s o p e r a t i v e a g a i n s t the e f f e c t s o f i n v a s i v e o r mucosal a s s o c i a t e d b a c t e r i a and t h a t low grade pathogens ( i . e .  the  intestinal  f l o r a ) e i t h e r a r e r e s t r i c t e d t o the gut lumen where immunological a c t i o n s a r e p r e v e n t e d o r d i s p l a y a low degree o f a n t i g e n i c i t y .  inter-  (Shedlofsky  and F r e t e r , 1 9 7 4 ) . 2.7.4  Non-Immunological F a c t o r s i n the S e c r e t i o n s o f the G . I . Several n o n - s p e c i f i c i n h i b i t o r s  Tract  o f b a c t e r i a l growth a r e  p r e s e n t i n the duodenal s e c r e t i o n s and i n m i l k o f t h e n u r s i n g i n d i v i d u a l . B i l e s a l t s a r e m e t a b o l i z e d by the r e s i d e n t b a c t e r i a and may form a n t i metabolites to c e r t a i n b a c t e r i a ( M c C l e l l a n d , 1979). lysozyme a r e both p r e s e n t i n i n t e s t i n a l s e c r e t o r y IgA, are b a c t e r i c i d a l 1971) .  (Hill  L a c t o f e r r i n and  s e c r e t i o n s and m i l k a n d , w i t h  and P o r t e r , 1 9 7 4 ; Knopf e t a l . ,  L a c t o f e r r i n , which i s commonly p r e s e n t i n m i l k c h e l a t e s  iron  which r e s t r i c t s b a c t e r i a l growth (Orson and R e i t e r , 1 9 8 1 ; B u l l e n e t a l . , 1972) .  Complement may be i n v o l v e d i n r e a c t i o n s i n o r n e a r the mucosa.  The a l t e r n a t e o r p r o p e r d i n pathway o f complement a c t i v a t i o n i s a c c e p t e d  33  as important in the defense against gram negative bacteria of the gut (Hood et a l . , 1978).  This is supported by the discovery that some  complement components are synthesized by the intestinal mucosa (Lai A Fat et a i . , 1976).  34 2.8  Humoral and C e l l u l a r Immunity i n P o r c i n e Mammary S e c r e t i o n s C o l o s t r u m i s t h e f l u i d s e c r e t e d by the mammary g l a n d d u r i n g  the f i r s t 24 hours ( K a r l s s o n , 1966) and m i l k i s s e c r e t e d d u r i n g remainder o f l a c t a t i o n .  the  IgG i s the p r i m a r y immunoglobulin component  o f serum and c o l o s t r u m ; IgA i s the p r i m a r y component o f m i l k ; and IgM i s a minor component o f b o t h .  In the f i r s t 24 hours IgG d e c r e a s e s f i v e -  f o l d and w i t h i n the f i r s t week i t from f o r m i n g 80% o f t o t a l  decreases t h i r t y - f o l d .  Thus i t  drops  c o l o s t r a l immunoglobulin t o 25% o f t o t a l  immunoglobulin ( C u r t i s and B o u r n e , 1 9 7 1 ) .  milk  IgA o n l y d e c r e a s e s t h r e e - f o l d  d u r i n g the f i r s t week and hence emerges as the major immunoglobulin  in  sow m i l k , a c c o u n t i n g f o r 50 t o 60% o f m i l k immunoglobulin ( C u r t i s and Bourne, 1971). Colostrum functions mainly i n protection against systemic i n f e c t i o n because the immunoglobulins i t the gut mucosa i n t o the c i r c u l a t i o n . d u r i n g which the p i g l e t  c o n t a i n s are absorbed through  This occurs i n a period of  i n t e s t i n e absorbs macromolecules i n t a c t  gut c l o s u r e a f t e r 24 t o 36 hours (Payne and M a r s h , 1 9 6 2 ) . c o p r a - a n t i b o d i e s which f u n c t i o n w i t h i n t h e i n t e s t i n a l  time  before  M i l k provides  lumen d u r i n g  the  p r e - w e a n i n g p e r i o d ( W i l s o n , 1974; B r a n d t z a e g , 1 9 7 3 ) . 125 Bourne and C u r t i s (1973) u s i n g  I labelled  immunoglobulin  determined the p r o p o r t i o n s o f serum d e r i v e d and l o c a l l y produced immunog l o b u l i n i n mammary s e c r e t i o n s .  They found t h a t a l l  colostral  IgG came  from the serum and t h a t 60% o f c o l o s t r a l IgA was s y n t h e s i z e d by the mammary g l a n d (a s m a l l p o r t i o n o f t o t a l  c o l o s t r a l immunoglobulins), and, conse-  q u e n t l y , c o n s i d e r e d t h a t c o l o s t r u m was a serum t r a n s u d a t e ( B o u r n e , 1973). They found t h a t m i l k , on the o t h e r h a n d , was a t r u e mammary s e c r e t i o n s i n c e  35  more than 90% o f the IgA and IgM and 70% o f IgG was produced l o c a l l y . In c o n j u n c t i o n w i t h i m m u n o g l o b u l i n s , p o r c i n e m i l k  contains  a t r y p s i n i n h i b i t o r w h i c h o c c u r s f i r s t l y a t h i g h l e v e l s and f a l l s t o a v e r y low l e v e l by the f i f t h day (Laskowski e t a l _ . , 1 9 5 7 ) . f u n c t i o n s to prevent degradation of c o l o s t r a l can be absorbed i n the i n t e s t i n e  T h i s probably  immunoglobulins b e f o r e they  (Scoot, 1972).  A l t h o u g h no i n f o r m a t i o n e x i s t s f o r p o r c i n e c o l o s t r u m , human c o l o s t r u m shows a r e l a t i v e l y h i g h l e v e l o f T lymphocytes and macrophages (Parmely and B e e r , 1 9 7 7 ) .  Parmely and Beer suggested t h a t i t  but not p r o v e n , t h a t t h e s e c e l l s c o u l d s u r v i v e i n the tract.  was p o s s i b l e ,  gastro-intestinal  They f u r t h e r suggested t h a t the mammary t i s s u e may " p a c k a g e "  s p e c i f i c c e l l u l a r components i n the c o l o s t r u m to c o n t r i b u t e  t o immuno-  competency i n t h e neonate and t h a t t h i s c e l l mediated immunity  (CMI) from  the mammary g l a n d depended upon i n d u c t i v e e v e n t s a t d i s t a n t mucosal s u r f a c e ( b r o n c h i a l a s s o c i a t e d and gut a s s o c i a t e d lymphoid t i s s u e s ) .  36  2.9  Preweaning M o r t a l i t y In a s u r v e y o f t h e l i t e r a t u r e  from 1937 t o 1976 McCallum  (1977) found t h a t l e v e l s o f preweaning m o r t a l i t y  have c o n s i s t e n t l y  ranged between 18 and 30 p e r c e n t o f p i g s born ( i n c l u d i n g  stillbirths).  Two s t u d i e s (Fahmy and B e r n a r d , 1 9 7 1 ; E n g l i s h and S m i t h , 1974) t h a t 50 per c e n t o f t h e t o t a l preweaning m o r t a l i t y days o f a g e . mortality  occurred before 3  Pomeroy (1960) noted t h a t 7 0 . 2 per c e n t o f t o t a l  preweaning  o c c u r r e d b e f o r e 3 days o f a g e , and Jones (1972) r e c o r d e d 63.1  per cent.  T h u s , any a t t e m p t t o reduce m o r t a l i t y  days o f p o s t n a t a l 2.9.1  recorded  must a f f e c t  the  existence.  Causes o f Preweaning  Mortality  The causes were f a i r l y and a r e summarized i n T a b l e 2 . 3  c o n s i s t e n t among t h e a u t h o r s  cited  These a r e t r a u m a , s t a r v a t i o n ,  weakness, d i s e a s e , c o n g e n i t a l a b n o r m a l i t i e s , and o t h e r c a u s e s . i n v o l v e s c r u s h i n g o r t r a m p l i n g o f p i g s by the sow. reflect  earliest  general Trauma  Some o f the d a t a may  t h e e f f e c t o f o t h e r p r i m a r y causes p r e d i s p o s i n g trauma such as  malnutrition,  general weakness, or c h i l l i n g .  S t a r v a t i o n , a major  cause o f d e a t h , c o u l d r e s u l t from two d i f f e r e n t  contributing  primary  factors.  The f i r s t i s a g a l a c t i a o f t h e sow w h i c h , i n the s t u d i e s o f E n g l i s h and Smith (1974) c o n t r i b u t e d t o 27 p e r c e n t o f the s t a r v a t i o n . factor,  contributing  The o t h e r  73 per c e n t , i s s e v e r e c o m p e t i t i o n w i t h i n  litters  due e i t h e r t o supernumary p i g s i n r e l a t i o n t o a v a i l a b l e t e a t s o r t o parity  in birthweights  dis-  which r e s u l t s i n unequal c o m p e t i t i v e advantage  h e a v i e r p i g s ( E n g l i s h and S m i t h , 1 9 7 4 ) .  The common r e s u l t o f  for  starvation  i s hypoglycaemia ( S h a r p e , 1 9 6 6 ; Edwards, 1972) which may be a g g r a v a t e d by chilling  ( C u r t i s , 1974).  General weakness, which c o n t r i b u t e s  to  high  Table 2 . 4  A Summary o f Major Causes C o n t r i b u t i n g to Death i n Baby P i g s (per cent  Reference  Trauma  Sharpe (1966)  21.2  17.1  9.6  9.6  2.1  40.4  Fahmy and Bernard (1971)  19.2  —  26.9  17.5  14.2  22.2  E n g l i s h and Smith (1974)  18.2  42.8  14.9  —  12.3  11.8  Rodeffer et a l . ,  30.9  17.6  14.7  18.2  —  13.1  (1975F  Starvation  Relative Weakness  Disease  contribution)  Congenital Abnormality  Other  38 losses, is most clearly associated with parturition aberrations of which the most common result is prenatal anoxia or hypoxia (English and Smith, 1974).  "Parturition aberrations" include premature umbilical cord rupture  and a prolonged farrowing interval between births (Rodeffer e_t aJL. 1975) Disease, as a cause of death, includes different diseases depending on the study. septicaemia.  Sharpe (1966) listed the major causes as gastroenteritis and Fahmy and Bernard (1971) listed scours and pneumonia as  major disease factors. gastroenteritis  Rodeffer et al_., (1975) listed transmissable  (T.G.E.), other diarrheas, and pneumonia.  abnormalities varied among the studies.  Congenital  English and Smith (1974) listed  the major traits including atresi ani, cardiac abnormality, congenital splay-leg, cleft palate, and hypoplasia kidney. 2.9.2  Effect of Low Birthweight on Survival "The effect of birth weight on survival is essentially linear  within a wide range of values" (Bereskin et al_.» 1973).  Thus, low birth-  weight is a major contributing factor to reducing survival (Sharpe, 1966;; Fahmy and Bernard, 1971; Bereskin_et al_., 1973).  Table 2.4  lists  mortality values found for low birthweight pigs by several researchers. These high mortality rates may vary with strain of pig or environment which, in turn, may include temperature and milking a b i l i t y of the sow (Pomeroy, 1960).  These high mortality rates reflect a greater susceptibility to  the major causes of death.  There was a higher incidence of trauma in low  birthweight pigs (Sharpe, 1966); a markedly higher incidence of starvation (Sharpe, 1966; English and Smith, 1974); and low birthweight had some effect on the incidence of septicaemia (Sharpe, 1966). weight pigs are much more susceptible to chilling.  Also, low birth-  Newland et al_., (1952)  Table 2 . 5  E f f e c t o f B i r t h Weight on M o r t a l i t y  Reference  Weight Range  P e r Cent M o r t a l i t y  Pomeroy (1960)  <900g  8 3 . 0 ( b e f o r e 3 days)  Sharpe (1966)  <800g  82.1  Fahmy and Bernard (1971)  <910g  60.0  <907g  74.6  (  E n g l i s h and Smith (1974)  VO  40 found that the drop in body temperature after chilling was inversely related to body weight. Pomeroy (1960) cited three factors contributing to higher mortality in low birth weight pigs: 1.  they may be less vigorous and active, and less competitive  at the teats during nursing. 2.  they have a larger surface area in relation to body weight.  Therefore there is a relatively greater heat loss per unit of body weight. 3.  they may be physiologically immature.  41  Foot-Notes 1.  Immunocytes include a l l cells of the immune system.  2.  The failure of the immune system, as a result of previous contact with antigen, to respond to the same antigen, although capable of responding to tohers. Tolerance is best established by neonatal injection of an antigen (Benaceraf and Unanue, 1979).  3.  An exotoxin is a soluble poisonous substance passing into the medium during growth of a microorganism. An endotoxin is a poisonous substance present in bacteria but separable from the cell body only on its disintegration. An enterotoxin is a toxin of bacteria produced within and affecting the intestine. (Websters 7th New Collegiate dictionary, 1965)  42  3.  Experimental  3.1  Introduction C o l o s t r u m - d e p r i v e d p i g s have been s u c c e s s f u l l y r e a r e d i n a  n o n - i s o l a t e d environment s i n c e 1961 (Owen e t a l _ . , 1 9 6 1 ) . Owen and B e l l  A f t e r work by  ( 1 9 6 4 ) , S c o o t ( 1 9 7 2 ) , and McCallum ( 1 9 7 7 ) , McCallum (1977)  c o n c l u d e d t h a t i t was p o s s i b l e " t o r a i s e c o l o s t r u m - d e p r i v e d n e o n a t a l p i g s i n an o r d i n a r y swine barn environment and a c h i e v e s u r v i v a l  rates  comparable t o t h o s e p r e s e n t l y t o l e r a t e d under n a t u r a l c o n d i t i o n s " u s i n g a b a t t o i r s e r u m - d e r i v e d immunoglobulins i n m i l k r e p l a c e r s . Both S c o o t (1972) and McCallum (1977) c o n c l u d e d t h a t o r a l a d m i n i s t r a t i o n o f 10 grams p e r k i l o g r a m o f body w e i g h t o f  immunoglobulins  on the f i r s t day f o l l o w e d by 2 grams p e r k i l o g r a m on s u c c e e d i n g days c o u l d c o n f e r adequate p a s s i v e immunity on c o l o s t r u m - d e p r i v e d p i g s . S c o o t (1972) found t h a t a d m i n i s t r a t i o n o f immunoglobulins o v e r 21 days i n c r e a s e d s u r v i v a l compared t o 10 day t r e a t m e n t  (from 75 p e r c e n t t o  88 per c e n t ) and McCallum (1977) observed a sharp i n c r e a s e i n  mortality  f o l l o w i n g removal o f immunoglobulin a f t e r 10 days compared t o those c o n t i n u e d on t r e a t m e n t f o r 20 d a y s . The purpose o f e x p e r i m e n t s r e p o r t e d h e r e i n was t o e v a l u a t e the e f f e c t o f o r a l l y a d m i n i s t e r e d immunoglobulins on c o l o s t r u m - d e p r i v e d p i g s o f low b i r t h w e i g h t . the a r t i f i c i a l  E x p e r i m e n t s o f Lodge and E l l i o t ( 1 9 7 9 ) , u s i n g  r e a r i n g t e c h n i q u e o f McCallum e t a l . , ( 1 9 7 7 ) , found t h a t  21 day w e i g h t , 56 day w e i g h t and age a t 9 0 k g . were h i g h l y with birthweight, artificial  but t h a t low b i r t h w e i g h t  r e a r i n g than under n a t u r a l  a l s o found t h a t a r t i f i c i a l pigs.  correlated  was l e s s i n h i b i t i n g  rearing.  under  Lodge and E l l i o t  r e a r i n g reduced m o r t a l i t y  o f low  (1979)  birthweight  43  The t r i a l s d e s c r i b e d h e r e i n were c a r r i e d environment on a commercial  farm  1  i n an e n v i r o n m e n t a l l y c o n t r o l l e d  room a d j a c e n t to the f a r r o w i n g rooms. carried and  out i n a barn  A s e r i e s o f 4 experiments was  out t o determine e f f e c t s o f low b i r t h weight on s u r v i v a l  growth.  44  3.2  Experiment I  3.2.1  Objective The o b j e c t i v e o f t h i s experiment .was t o a s s e s s the e f f i c a c y  of  a b a t t o i r d e r i v e d p o r c i n e immunoglobulin e x t r a c t  from serum as a m i l k  r e p l a c e r a d d i t i v e f o r r e a r i n g low b i r t h w e i g h t p i g s . 3.2.2  M a t e r i a l s and Methods  3.2.2.1  Experimental Animals T w e n t y - f o u r low b i r t h w e i g h t p i g s w e i g h i n g l e s s than lOOOg  o f Y o r k s h i r e X Landrace b r e e d i n g were a l l o t t e d w i t h i n a t e n day p e r i o d . F a r r o w i n g s were a t t e n d e d and e x p e r i m e n t a l p i g s were removed from the sow a t b i r t h o r 12 hours l a t e r .  P i g s were weighed a t b i r t h , e a r t a g g e d , and  i n d i v i d u a l l y penned i n a n u r s e r y room. treatments.  Cages were a d j o i n i n g w i r e mesh 46cm x 25cm x 20cm i n two  P r i o r t o the t r i a l infected.  P i g s were randomly a s s i g n e d t o tiers.  the room and cages were t h o r o u g h l y c l e a n e d and d i s -  Cages were washed p e r i o d i c a l l y d u r i n g the t r i a l .  i n the n u r s e r y room was m a i n t a i n e d between 30°C and 33°C.  Temperature A l l pigs received  i r o n d e x t r a n i n j e c t i o n s and had t h e i r n e e d l e t e e t h and t a i l s c l i p p e d a t two days o f a g e . 3.2.2.2  A second i r o n d e x t r a n i n j e c t i o n was g i v e n a t 10 days o f a g e .  P r e p a r a t i o n o f P o r c i n e Immunoglobulins Immunoglobulins used i n a l l t r i a l s were p r e p a r e d by Canada  Packers L t d . , Toronto, O n t a r i o . 40 per c e n t s a t u r a t i o n w i t h  ( N H  The immunoglobulin - f r a c t i o n d e r i v e d a t 4  )  2  SO^ was washed, d i a l y z e d , mixed w i t h  condensed whole m i l k and s p r a y d r i e d 3.2.2.3  (Owen, p e r s o n a l  communication).  D i e t a r y Treatments In a l l  t r e a t m e n t s , p i g s r e c e i v e d a non-medicated commercial  2 milk replacer  .  Feed i n t a k e was a d j u s t e d t o 7 . 5 p e r c e n t o f t h e i r  body  45  w e i g h t i n a i r d r y m a t t e r which was d i l u t e d 1 : 4  with water.  For the  3 days d i e t s were f o r m u l a t e d w i t h a 10 per c e n t d e x t r o s e s o l u t i o n .  first  Pigs  were weighed e v e r y o t h e r day and f e e d a l l o w a n c e s were a d j u s t e d a c c o r d i n g l y . Immunoglobulin was mixed w i t h the m i l k r e p l a c e r and f e d a t l e v e l s s e t out i n the f o l l o w i n g s c h e d u l e : 1.  No c o l o s t r u m , m i l k r e p l a c e r o n l y .  2.  C o l o s t r u m f o r 12 h o u r s , f o l l o w e d by m i l k r e p l a c e r o n l y .  3.  C o l o s t r u m f o r 12 h o u r s , p l u s immunoglobulin a t 2 g / k g body weight/day f o r 9.5 days.  4.  Immunoglobulin e x t r a c t on f i r s t day ( l O g / k g body w e i g h t ) , p l u s immunoglobulin ( 2 g / k g body w e i g h t / d a y )  for 9 days.  S c o u r i n g a n i m a l s were t r e a t e d , as n e c e s s a r y , on an i n d i v i d u a l 3 p i g b a s i s w i t h Furoxone 3.2.2.4  .  The t r i a l was o f 21 days d u r a t i o n .  F e e d i n g Regimen S i n c e the p i g s would n o t f e e d from s h a l l o w bowls  after birth, feed.  t h e y were f o r c e f e d w i t h s y r i n g e s u n t i l they would n i p p l e  In l a t e r t r i a l s  this t r i a l  immediately  n i p p l e f e e d i n g was s u c c e s s f u l from b i r t h but  some d i f f i c u l t y  was e n c o u n t e r e d .  were s w i t c h e d t o s h a l l o w b o w l s .  A t 10 days o f age a l l  Feeding was e v e r y 2 hours f o r the  during pigs first  4 d a y s , e v e r y 4 hours on days 5 t o 8 and e v e r y 6 hours from days 9 to 2 1 . F r e s h w a t e r was made a v a i l a b l e from day 5 and c r e e p f e e d was o f f e r e d d a i l y a f t e r 10 days o f a g e . 3.2.3  fresh  Measurements and O b s e r v a t i o n s P i g s were weighed e v e r y 2 d a y s .  M o r t a l i t y was r e c o r d e d and  p o s t mortems were c a r r i e d o u t on a l l dead p i g s by the P r o v i n c i a l V e t e r i n a r y Laboratory, Abbotsford, B.C.  Infectious  agents and c a u s a t i v e f a c t o r s were  46 i d e n t i f i e d whenever p o s s i b l e . M o r t a l i t y was analyzed  s t a t i s t i c a l l y by g i v i n g a s u r v i v o r  a zero value and a dead p i g a 1 v a l u e . v a r i a n c e (ANOVA) with the d e s i g n model  The a n a l y s i s used was a n a l y s i s o f being:  Y^j = p + T- + e ^ j where T.. = Treatment  Effects  y = P o p u l a t i o n Mean £.. = Experimental  Error  Rate o f g a i n was a l s o analyzed with t h i s model. The  mean b i r t h - w e i g h t s o f s u r v i v o r s and dead p i g s were  compared with a " t " t e s t 3.2.4  ( C h o i , 1978).  R e s u l t s and D i s c u s s i o n M o r t a l i t y was high  negative control  group dying b e f o r e 10 days o f age.  c o l o s t r u m p l u s supplemental highest s u r v i v a l . (P  0.05).  h i g h e r than  (Table 3.1.b) w i t h a l l p i g s i n the  The  immunoglobulin e x t r a c t f o r 10 days showed the  The d i f f e r e n c e s between treatments  t h a t o f the dead p i g s (P  The  0.01).  septicaemia.  trial. aspiration  r e g a r d l e s s o f treatment,  have i n v o l v e d E. c o l i  caused  introduced  A major c h a r a c t e r i s t i c o f dead p i g s ,  was a f l a c c i d , d i l a t e d  The cause o f t h i s  pneumonia  The pneumonia was i n v a r i a b l y  o f f o r e i g n m a t e r i a l i n the bronchi and lungs  w h i l e f o r c e f e e d i n g with s y r i n g e s .  stomach.  significantly  T h i s d i f f e r e n c e suggests  cause o f death was predominantly  by E. c o l i  by the presence  were not s i g n i f i c a n t  mean b i r t h - w e i g h t o f the s u r v i v i o r s was  h i g h e r b i r t h - w e i g h t p i g s had an advantage i n t h i s  complicated  Those which r e c e i v e d  i n t e s t i n e or distended  s t a t e c o u l d have been o v e r - f e e d i n g and c o u l d  enteritis.  A l l p i g s were d i a r r h e t i c b e f o r  death.  Most p i g s which d i e d showed a marked l a c k o f depot f a t i n d i c a t i n g no e n e r g e t i c r e s e r v e s f o r s u r v i v a l , and  that  47 Table 3.1a  Experiment 1: E x p e r i m e n t a l A n i m a l s  Treatment  Number i n Treatment Group  Mean B i r t h - W e i g h t t S.D.  No c o l o s t r u m ; no immunoglobulin  6  765 ± 157 g  C o l o s t r u m ; no immunoglobulin  6  854 + 121 g  C o l o s t r u m + immunoglobulin (2g/kg/day)  6  843 + 190 g  Immunoglobulin ( l O g / k g / d a y to 2 g / k g / d a y )  6  752 + 190 g  T a b l e 3.1b  Experiment 1: R e s u l t s  Treatment  % Survival % Survival t o Day 10 to Day 21  Rate o f Gain ( q/day )  No c o l o s t r u m ; no immunoglobulin  0  C o l o s t r u m ; no immunoglobulin  33  33  46.5 + 24.2  C o l o s t r u m + immunoglobulin (2g/kg/day)  50  50  42.1 + 23.5  Immunoglobulin ( l O g / k g / d a y to 2 g / k g / d a y )  16  16  7 . 5 (1 p i g ) -  48  dehydration, no doubt a result of the diarrhea. A higher level of disease carrying microbes in the environment might have been present due to the reservoir of infection carried by the negative control animals which were a l l i l l from the beginning of the trial.  Sanitation and high moisture levels were difficult to control by  washing the cages.  The resulting moist, humid, and non-sterile conditions  may have been ideal for the growth of microbes. It was assumed that a 12 hour nursing period was adequate for attaining sufficient immunoglobulin levels in the plasma. supported by work of Scoot (1972) and Carlson and Lecce (1973).  This is  49  3.3  Experiment  3.3.1  Objective  II  The o b j e c t i v e o f t h i s experiment was t o f u r t h e r a s s e s s the e f f i c a c y o f a b b a t o i r d e r i v e d p o r c i n e serum immunoglobulin e x t r a c t as a m i l k r e p l a c e r a d d i t i v e f o r r e a r i n g low b i r t h w e i g h t p i g s .  To reduce the  pool o f i n f e c t i o n , n e g a t i v e c o n t r o l s r e c e i v i n g no immunoglobulins o r c o l o s t r u m d e r i v e d ) were not i n c l u d e d i n t h i s 3.3.2  M a t e r i a l s and Methods  3.3.2.1  Experimental Animals  (artificial  trial.  T w e n t y - f o u r low b i r t h w e i g h t p i g s w e i g h i n g l e s s than lOOOg o f Y o r k s h i r e X Landrace b r e e d i n g were a l l o t t e d w i t h i n a t e n day p e r i o d . F a r r o w i n g s were a t t e n d e d and e x p e r i m e n t a l a n i m a l s were removed a t o r 12 hours l a t e r .  P i g s were weighed a t b i r t h , e a r t a g g e d , and i n d i v i d u a l l y  penned i n a n u r s e r y room.  P i g s were randomly a s s i g n e d t o t r e a t m e n t s .  were a d j o i n i n g w i r e mesh 46cm x 25cm x 20cm i n two t i e r s . trial  birth  P r i o r to  the room and cages were t h o r o u g h l y c l e a n e d and d i s i n f e c t e d .  were l e f t unwashed t h r o u g h o u t t h e t r i a l p e r i o d . room was m a i n t a i n e d between 30°C and 33°C.  Cages the  Cages  Temperature i n t h e n u r s e r y  A l l pigs received iron  dextran  i n j e c t i o n s and had t h e i r n e e d l e t e e t h and t a i l s c l i p p e d a t two days o f a g e . A second i r o n d e x t r a n i n j e c t i o n was g i v e n a t 10 days o f a g e . 3.3.2.2  D i e t a r y Treatments 2 P i g s r e c e i v e d a non-medicated commercial m i l k r e p l a c e r  .  Feed i n t a k e was reduced from t h e l e v e l i n e x p e r i m e n t I t o 6 per c e n t o f body w e i g h t i n a i r dry m a t t e r which was d i l u t e d 1 : 4 w i t h w a t e r .  For  t h e f i r s t 3 days d i e t s were f o r m u l a t e d w i t h a 10 per c e n t d e x t r o s e s o l u t i o n . P i g s were weighed e v e r y o t h e r day and feed a l l o w a n c e s were a d j u s t e d a c c o r d -  50 ingly. at  Immunoglobulin e x t r a c t was mixed with the m i l k r e p l a c e r and f e d  l e v e l s s e t o u t i n the f o l l o w i n g schedule o f t r e a t m e n t s : 1.  Colostrum f o r 12 hours, f o l l o w e d by m i l k r e p l a c e r o n l y .  2.  Colostrum f o r 12 hours, f o l l o w e d by immunoglobulin 2g/kg body weight/day  3.  Immunoglobulin  f o r 9.5 days.  (lOg/kg body weight) on the f i r s t  by immunoglobulin  at  a t 2g/kg body weight/day  day f o l l o w e d  f o r 9.5 days.  S c o u r i n g animals were t r e a t e d , as n e c e s s a r y , on an 4 individual  p i g basis with A n i s t a t  , a broad spectrum  antibiotic.  The t r i a l  was o f 21 days d u r a t i o n . 3.3.2.3  Feeding Regimen Pigs were n i p p l e f e d dor one week then changed to bowl  f e e d i n g f o r the remainder the f i r s t  o f the t r i a l .  Feeding was every 2 hours f o r  4 days, every 4 hours on days 5 t o 8, and every 6 hours  days 9 to 21.  from  Fresh water was a v a i l a b l e to them from day 5 and creep  feed was o f f e r e d f r e s h d a i l y a f t e r 10 days o f age. 3.3.3  Measurements and O b s e r v a t i o n s P i g s were weighed e v e r y 2 days.  and post mortems were conducted  M o r t a l i t y was r e c o r d e d  on a l l dead p i g s by the P r o v i n c i a l  V e t e r i n a r y L a b o r a t o r y , A b b o t s f o r d , B.C..  I n f e c t i o u s agents and c a u s a t i v e  f a c t o r s were i d e n t i f i e d whenever p o s s i b l e . M o r t a l i t y and r a t e o f g a i n were a n a l y s e d as i n Experiment 1, u s i n g a n a l y s i s o f v a r i a n c e .  The mean b i r t h weights o f s u r v i v o r s and dead  p i g s were compared w i t h a " t " t e s t ( C h o i ,  1978).  51  3.3.4  Results  and  Discussion  Mortality i n Experiment 1. o f the  T h i s may  negative control  environmental  (Table be  3.2.b) decreased from the  level  a t t r i b u t e d to improved t e c h n i q u e ,  group (as a pool o f i n f e c t i o n ) , and  conditions.  hours showed a m o r t a l i t y  achieved  The  group r e c e i v i n g o n l y  r a t e a t 21  0.05).  elimination  improved  colostrum f o r  12  days s i g n i f i c a n t l y h i g h e r than  o t h e r two  groups (P  There was  mortality  between thos r e c e i v i n g c o l o s t r u m with immunoglobulin and  r e c e i v i n g immunoglobulin e x t r a c t S i n c e i t was per  no  s i g n i f i c a n t difference  instead of  level  of feeding  o f body weight i n a i r dry matter, and  and  i n the could  i n the  stomach o f the  stomach.  then pass to the i n the  gastric  i n t e s t i n e and  gastric acid secretion  e x a c e r b a t i n g the  There was o f s u r v i v i n g versus dead  no  could  producing  for coliforms  a l s o l e a d to  pH  which  Endotoxin reduced  conditions.  significant difference  pigs.  between  , with r e s u l t a n t high  cause a scour syndrome.  stomach by c o l i f o r m b a c t e r i a  cent  always preceded  A lack of l a c t i c a c i d pig  7.5  consequently reduced.  t h a t scour was  achlorhydric  at  reduced to 6 per  stomach, might l e a d to r a p i d growth c o n d i t i o n s  release  possible  They found t h a t a d i r e c t r e l a t i o n s h i p e x i s t e d  growth o f b a c t e r i a  organisms i n the  was  t h i s problem was  White e t a l _ . , (1969) found i n t h e i r t r i a l s ,  pH  those  colostrum.  cent o f body weight l e d to a d i s t e n d e d stomach and  by g a s t r i c s t a s i s .  in  observed i n Experiment 1 t h a t f e e d i n g  s t a s i s producing s c o u r s , the  the  between b i r t h weights  52  Table 3.2a  Experiment 2; Experimental Animals  Treatment  Number i n Treatment Group  Mean Birth-weight ± S.D.  Colostrum; no immunoglobulin  8  677 ± 111 g  Colostrum + immunoglobulin (2g/kg/day)  8  707 ± 170 g  Immunoglobulin to 2g/kg/day)  8  736 ± 143 g  Table 3.2b  (lOg/kg/day  Experiment 2: Results  Treatment  % Survival % Survival to Day 10 to Day 21  Colostrum; no immunoglobulin  37  0  Colostrum + immunoglobulin (2g/kg/day)  75  63^  35.2 + 15.4 g  Immunoglobulin to 2g/kg/day)  63  50  39.8 ± 16.9 g  (lOg/kg/day  b  Rate of Gain ( g/day )  ( d i f f e r i n g superscripts denote s t a t i s t i c a l l y d i f f e r e n t values at P= .05 )  53  Causes o f m o r t a l i t y were g e n e r a l s e p t i c a e m i a f o r 6 p i g s p r o b a b l y due to c o l i f o r m i n f e c t i o n , d e f i n i t e 3 p i g s , and c o l i f o r m e n t e r i t i s  coliform septicaemia  with septicaemia f o r 7 p i g s .  for  A l l dead  p i g s showed c h a r a c t e r i s t i c s o f e m a c i a t i o n and d e h y d r a t i o n which may be a r e s u l t o f the d i a r r h e a which o c c u r r e d i n a l l a n i m a l s which d i e d . Rate o f g a i n d i d not d i f f e r s i g n i f i c a n t l y  between the  two groups o f s u r v i v i n g p i g s ( T a b l e 3.2 b ) and o v e r a l l remained a t a v e r y low l e v e l .  Consumption o f c r e e p f e e d and w a t e r s u p p l i e d ad l i b i t u m  c o u l d not be weighed a c c u r a t e l y because o f w a s t a g e .  54 3.4  Experiment  3.4.1  Objective  III  The o b j e c t i v e o f t h i s experiment was to compare a lower l e v e l o f immunoglobulin e x t r a c t a d m i n i s t r a t i o n ,  ( l O g / k g body w e i g h t  f o r the f i r s t day f o l l o w e d by 2 g / k g body w e i g h t / d a y f o r 9 days) w i t h a  hioher  immunoglobulin l e v e l  ( 1 5 g / k g body w e i g h t f o r the  day f o l l o w e d by 5g/kg body w e i g h t / d a y ) .  first  Treatment groups o f p i g s  n u r s i n g c o l o s t r u m f o r 12 hours i n s t e a d o f h i g h i n i t i a l  doses o f immuno-  g l o b u l i n were a l s o i n c l u d e d f o r c o m p a r i s o n . 3.4.2  M a t e r i a l s and Methods  3.4.2.1  Experimental Animals Two c o n s e c u t i v e r e p l i c a t e s were c a r r i e d o u t .  To each  r e p l i c a t e 24 low b i r t h w e i g h t p i g s o f l e s s than lOOOg o f Y o r k s h i r e X Landrace b r e e d i n g were a l l o t t e d w i t h i n a 10 day p e r i o d .  Farrowings were  a t t e n d e d and e x p e r i m e n t a l p i g s were removed a t b i r t h o r 12 hours  later.  P i g s were weighed a t b i r t h , e a r t a g g e d , and i n d i v i d u a l l y penned i n a n u r s e r y room.  P i g s were randomly a s s i g n e d t o t r e a t m e n t s .  a d j o i n i n g w i r e mesh 46cm x 25cm x 20cm i n two t i e r s .  Cages were  P r i o r to the  the room and cages were t h o r o u g h l y c l e a n e d and d i s i n f e c t e d . l e f t unwashed t h r o u g h o u t the t r i a l  period.  was m a i n t a i n e d between 30°C and 33°C.  trial  Cages were  Temperature i n the n u r s e r y  A l l pigs received iron  dextran  i n j e c t i o n s and had t h e i r n e e d l e t e e t h and t a i l s c l i p p e d a t two days o f age.  A second i r o n d e x t r a n i n j e c t i o n was g i v e n a t 10 days o f a g e .  3.4.2.2  D i e t a r y Treatments 2 P i g s r e c e i v e d a non-medicated commercial m i l k r e p l a c e r  .  Feed i n t a k e was s e t a t 6% o f body w e i g h t of a i r dry m a t t e r which was d i l u t e d  55  1 : 4 w i t h water. per  For the f i r s t  cent d e x t r o s e s o l u t i o n .  accordingly.  3 days d i e t s were f o r m u l a t e d w i t h a 10  Pigs were weighed  Immunoglobulin  every o t h e r day and f e d  e x t r a c t was mixed w i t h the m i l k r e p l a c e r  and f e d a t l e v e l s s e t o u t i n the f o l l o w i n g schedule o f t r e a t m e n t s : 1.  15g/kg bodyweight  immunoglobulin  on the f i r s t  day f o l l o w e d  by 5g/kg body weight/day f o r 9 days. 2.  lOg/kg body weight immunoglobulin on the f i r s t day f o l l o w e d by 2g/kg body weight/day f o r 9 days.  3.  12 hours o f c o l o s t r u m n u r s i n g f o l l o w e d by 9.5 days o f immunoglobulin  4.  a t 5g/kg body weight/day.  12 hours o f c o l o s t r u m n u r s i n g f o l l o w e d by 9.5 days o f immunoglobulin In  replicate  a t 2g/kg/day.  1 the a n t i b i o t i c A n i s t a t  4  was used.  In  3 r e p l i c a t e 2 the a n t i b a c t e r i a l 3.4.2.3  Furoxone  was used.  Feeding Regimen Pigs were n i p p l e f e d f o r one week then changed  f e e d i n g f o r the remainder o f the t r i a l .  to bowl  Feeding was every 2 hours f o r the  f i r s t 4 days, every 4 hours on days 5 to 8, and every 6 hours from days 9 to  21.  Fresh water was a v a i l a b l e from day 5 and creep feed was o f f e r e d  f r e s h d a i l y a f t e r 10 days o f age. 3.4.3  Measurments and O b s e r v a t i o n s Measurments and s t a t i s t i c a l  the  a n a l y s e s were the same as i n  two p r e v i o u s experiments except t h a t another dependant  included, frequency o f scouring.  v a r i a b l e was  The d e s i g n was a randomized b l o c k d e s i g n  s i n c e two r e p l i c a t e s were c a r r i e d o u t .  56  3.4.4  Results  and  Discussion  Mortality  (Table  3.3..b) was s i m i l a r to t h a t  2 where i t was a p p r o x i m a t e l y 50 per cent i n the t r e a t e d was no s i g n i f i c a n t d i f f e r e n c e the  r e c e i v i n g a higher l e v e l level. on  groups.  There  between treatments f o r m o r t a l i t y .  Thus,  r e s u l t s i n d i c a t e d no s i g n i f i c a n t d i f f e r e n c e  c o l o s t r u m and those r e c e i v i n g  i n Experiment  between those  receiving  immunoglobulin e x t r a c t , o r between those  o f immunoglobulin and thowe r e c e i v i n g a lower  The assumption t h a t  12 hours o f n u r s i n g  the f i n d i n g s o f Scoot (1972) and C a r l s o n  was adequate was based  and Lecce (1973).  This  assumption r e l i e s on the p i g r e c e i v i n g adequate c o l o s t r u m during However, low b i r t h weight pigs a r e f r e q u e n t l y not  being as c o m p e t i t i v e o r n o t being a b l e  some cases w i t h i n level  this t r i a l ,  o f systemic passive  t o reach a t e a t .  i n d i v i d u a l s may not r e c e i v e  immunity which may l e a d  i n f e c t i o n a f f e c t i n g the m o r t a l i t y  rate.  artificial  instead  survival  disadvantaged  immunoglobulin e x t r a c t  in this  an adequate  to s u s c e p t i b i l i t y to  As was the c a s e , those  that  receiving  o f c o l o s t r u m , showed a high  d i f f e r e n c e between mean b i r t h weights o f s u r v i v o r s I t was observed  respect,  Thus, i n  b e f o r e day 10, but the d i f f e r e n c e was not s i g n i f i c a n t .  significant.  nursing.  The  and dead pigs was not  57 T a b l e 3.3a  Experiment 3: E x p e r i m e n t a l Animals  R e p l i c a t e Treatment  2  Number i n T r e a t ment Group  Mean B i r t h - W e i g h t ± S.D.  Immunoglobulin (15g/kg /day t o 5g/kg/day)  6  761 ± 166 g  Immunoglobulin (lOg/kg /day t o 2g/kg/day)  6  729 ± 227 g  Colostrum + immunog l o b u l i n (5g/kg/day)  6  835 + 99 g  Colostrum + immunog l o b u l i n (2g/kg/day)  6  746 ± 192 g  Immunoglobulin 5 g/kg/day)  (15 t o  6  814 ± 83 g  Immunoglobulin 2 g/kg/day)  (10 t o  6  671 + 96 g  Colostrum + immunog l o b u l i n (5g/kg/day)  6  704 ± 218 g  Colostrum + immunog l o b u l i n (2g/kg/day)  6  834 i 59 g  Table 3.3b  Experiment 3: Experimental  Results  Replicate  Treatments  % Survival % Survival - to Day 10~~~ to Day 21  Rate of Gain (g/day)  1  15 g/kg for Day 1 then 5 g/kg/day for 9 days  50  46.3 + 4.0  10 g/kg for Day 1 then the 2 g/kg/day for 9 days  50  39.7 ± 1.2  b  Colostrum for 12 h hrs. rs.; 5g/kg/day for 9.5 days  33  51.5 ± 0.7  a  Colostrum for 12 h r s . ; 2g/kg/day for 9.5 days  66  55.3 + 8.8  a  3.3  15 g/kg for Day 1 then 5 g/kg/day for 9 days  50  55.7 + 3.5  a  9  10 g/kg for Day.1 then 2 g/kg/day for 9 days  83  55.7 ± 3.5  a  Colostrum for 12 h r s . ; 5 g/kg/day for 9.5 days  17  59.0(1 only)" 15  Colostrum for 12 h r s . ; 2 g/kg/day for 9.5 days  50  60.0 ± 8.7  •  Combined  a  Scouring Frequency days scouring/survivor) Mean Scouring Frequency 7 5.3 5 5.0 + 2.6  C  8.9 + 3.5  d  8.8  7  a  15 g/kg for Day 1 then 5 g/kg/day for 9 days  84  50  51.0 ± 6 . l  a  10 g/kg for Day 1 ther then 2 g/kg/day for 9 days  84  66  41.0 ± 6.5  b  Colostrum for 12 h hrs.; rs.; 5 g/kg/day for 9.5 days  75  25  54.0 + 4.4  a  Colostrum for 12 h r s . ; 2 g/kg/day for 9.5 days  75  58  57.3 ± 8.4  a  co  59 under500g b i r t h w e i g h t t h e r e was no s u r v i v a l , however the number o f o b s e r v a t i o n s was f e w . Cause o f death d u r i n g the f i r s t r e p l i c a t e , i n 11 cases was S a l m o n e l l o s i s c a u s i n g d i a r r h e a and s e p t i c a e m i a . was i d e n t i f i e d as Group B  serotype  S a l m o n e l l a i n 4 cases w h i l e i n the r e m a i n i n g  cases s e r o t y p e was u n i d e n t i f i e d . enteritis.  The a c t u a l  In one case death was due to E . c o l i  D u r i n g the second r e p l i c a t e , S a l m o n e l l a were h e a v i l y i m p l i c a t e d ,  b u t , due t o the i n t e r f e r e n c e o f a n t i b i o t i c s g i v e n d u r i n g t r e a t m e n t , not be i s o l a t e d i n a l l  cases.  could  K l e b s i e l l a was a l s o i s o l a t e d from two p i g s .  Rate o f g a i n ( T a b l e 3 . 3 . b ) was i n c r e a s e d o v e r t h a t found i n Experiment I I .  Those r e c e i v i n g immunoglobulin a t the l o w e r l e v e l  showed a s i g n i f i c a n t l y l o w e r r a t e o f g a i n i n both r e p l i c a t e s (P = 0.05) ( F i g u r e s 3 . 1 . a and 3 . 1 . b ) .  S i n c e the p i g s r e c e i v i n g 2g/kg body w e i g h t /  day o f immunoglobulin a f t e r r e c e i v i n g c o l o s t r u m showed a s i g n i f i c a n t l y h i g h e r (P = 0.05) growth r a t e than those which r e c e i v e d a r t i f i c i a l  immuno-  g l o b u l i n ( l O g / k g body w e i g h t on the f i r s t day) i n s t e a d o f c o l o s t r u m , the e f f e c t may be due t o an i n s u f f i c i e n t f o r p a s s i v e s y s t e m i c immunity. growth r a t e , i t  initiating  dose o f l O g / k g body w e i g h t  However, even i f  t h i s treatment  d i d not show any s i g n i f i c a n t a f f e c t on m o r t a l i t y  affected rate.  Both S c o o t (1972) and McCallum (1977) found t h a t the h i g h e r dosage o f immunoglobulins (15 and 5 g / k g body w e i g h t / d a y ) slightly.  increased rate of gain  S c o o t (1972) i n d i c a t e s t h a t b l o o d g l o b u l i n l e v e l s were not as  high with a r t i f i c i a l l y  supplemented as w i t h sow nursed p i g s .  Frequency o f s c o u r i n g o f the s u r v i v o r s showed no s i g n i f i c a n t d i f f e r e n c e s between the s c h e d u l e d t r e a t m e n t s , however, the f r e q u e n c y o f s c o u r i n g was s i g n i f i c a n t l y d i f f e r e n t  between the two r e p l i c a t e s  (Table  Figure  3.1.a  Growth  i n Experiment  3,  Replicate  1  Fiqure 3.1.b  Growth in Experiment 3, Rep  2000  A -Colostrum + 2g/kg/day Ig m " + 5g/kg/day Ig 1500  • -10 to 2 g/kg/day Ig O -15 to 5 g/kg/day Ig  1000  U  If  IB  20  62 3.3.b). different  The o b v i o u s reason f o r t h i s d i f f e r e n c e seems to have been t h a t a n t i - s c o u r drugs were used i n each r e p l i c a t e s u g g e s t i n g t h a t  4 the a n t i b i o t i c A n i s t a t  was more e f f e c t i v e i n c o n t r o l l i n g s c o u r s than  3 the a n t i b a c t e r i a l  Furoxone  .  In both r e p l i c a t e s , the s c o u r i n g f r e q u e n c y  o f s u r v i v o r s i n c r e a s e d the h i g h e s t l e v e l a f t e r removal o f p i g s from immunoglobulin s u p p l e m e n t a t i o n a t 10 days o f age ( F i g u r e 3 . 2 ) . s u g g e s t s t h a t the p i g s r e q u i r e d f u r t h e r g l o b u l i n s beyond the t e n t h d a y .  This  p a s s i v e p r o t e c t i o n w i t h immuno-  Figure 3.2.  S c o u r i n g Frequency ( p e r c e n t o f s u r v i v o r s  scourinq)  100 A Experiment 3 ; R e p l i c a t e 1 A  Experiment 3 ; R e p l i c a t e 2  °  Experiment 4  A A A  O  A  A  2 _L_  1  8 JL  3 5 Days on T r i a l  A A  A A A  A  A  A L_  o J  11  1  13  o  O  L_  15  17  A  A J  I  19  21  64  3.5  Experiment IV  3.5.1  Objective The o b j e c t i v e o f t h i s e x p e r i m e n t was t o compare p e r i o d s  o f immunoglobulin f e e d i n g .  The p e r i o d s s e l e c t e d f o r comparison were  1 0 , 15 and 21 days on immunoglobulin e x t r a c t a t a l e v e l o f l O g / k g body w e i g h t f o r the f i r s t day f o l l o w e d by 2 g / k g body w e i g h t / d a y f o r 9 d a y s . 3.5.2  M a t e r i a l s and Methods  3.5.2.1  Experimental Animals T w e n t y - f o u r low b i r t h w e i g h t  p i g s o f l e s s than lOOOg o f  Y o r k s h i r e X Landrace b r e e d i n g were a l l o t t e d w i t h i n a ten day p e r i o d . F a r r o w i n g s were a t t e n d e d and e x p e r i m e n t a l p i g s were removed a t  birth.  P i g s were weighed a t b i r t h , e a r t a g g e d , and i n d i v i d u a l l y penned i n a n u r s e r y room.  P i g s were randomly a s s i g n e d to t r e a t m e n t s .  a d j o i n i n g w i r e mesh 46cm x 25cm x 20cm i n two t i e r s .  Cages were  P r i o r t o the  the room and cages were t h o r o u g h l y c l e a n e d and d i s i n f e c t e d . l e f t unwashed throughout  the t r i a l  period.  room was m a i n t a i n e d between 30°C and 33°C.  trial  Cages were  Temperature i n the n u r s e r y A l l pigs received iron  i n j e c t i o n s and had t h e i r n e e d l e t e e t h and t a i l s  dextran  c l i p p e d a t two days o f a g e .  A second i r o n d e x t r a n i n j e c t i o n was g i v e n a t 10 days o f a g e . 3.5.2.2  D i e t a r y Treatments 2 P i g s r e c e i v e d a n o n - m e d i c a t e d commercial m i l k r e p l a c e r  .  Feed i n t a k e was a d j u s t e d t o 6 per c e n t o f body w e i g h t i n a i r d r y m a t t e r w h i c h was d i l u t e d 1 : 4 w i t h w a t e r .  For the f i r s t 3 days d i e t s were  f o r m u l a t e d w i t h a 10 per c e n t d e x t r o s e s o l u t i o n .  P i g s were weighed e v e r y  o t h e r day and f e e d a l l o w a n c e s were a d j u s t e d a c c o r d i n g l y .  Immunoglobulin  was mixed w i t h the m i l k r e p l a c e r and f e d a t one l e v e l : l O g / k g body w e i g h t  65  on the f i r s t  day f o l l o w e d by 2g/kg body weight/day f o r succeeding days.  Three p e r i o d s o f immunoglobulin  f e e d i n g were a p p l i e d : 10 days, 15 days,  and 21 days. S c o u r i n g was  t r e a t e d , as n e c e s s a r y , on an i n d i v i d u a l p i g  3 b a s i s , w i t h Furoxone 3.5.2.3  .  Feeding Regimen Pigs were n i p p l e - f e d  Creep feed was  throughout the 21 day t r i a l  o f f e r e d from day 10 but water was  o n l y , by b o t t l e , to prevent s p i l l a g e . first  offered  Feeding was  period.  periodically,  every 2 hours f o r the  4 days, every 4 hours on days 5 to 8 and every 6 hours from days  9 to 21. 3.5.3  Measurements and O b s e r v a t i o n s Pigs were weighed  e v e r y 2 days.  M o r t a l i t y was r e c o r d e d  and post mortems were conducted on a l l dead pigs by the P r o v i n c i a l V e t e r i n a r y L a b o r a t o r y , A b b o t s f o r d , B.C.  I n f e c t i o u s agents and  causative  f a c t o r s were i d e n t i f i e d whenever p o s s i b l e . M o r t a l i t y , r a t e o f g a i n , and frequency o f s c o u r i n g ( f o r s u r v i v o r s ) were s t a t i s t i c a l l y the  analysed with a n a l y s i s of variance  same model as i n Experiment 1.  using  A l s o the mean b i r t h weights o f ;  s u r v i v o r s and dead p i g s were compared w i t h a " t " t e s t . 3.5.4  R e s u l t s and  Discussion  Mortality rate  (Table 3.4.b) improved compared to p r e v i o u s  66  Table 3.4a  Experiment 4 : E x p e r i m e n t a l  Treatment  Animals  Number i n Treatment  Mean  Group  t S.D.  10 days on immunoglobulin  8  674 + 148 g .  15 days on immunoglobulin  8  708 + 111 g .  21 days on immunoglobulin  8  749 + 116 g .  T a b l e 3.4b  Experiment 4 :  Birth-weight  Results  Treatment  % Survival t o Day 10  % Survival t o Day 21  Rate o f Gain (g/day)  10 days  63  50  40.8 + 2 3 . 2  15 days  100  8R  21 days  100  100  a  a b  b  c d  Frequency o f Scouring (Days s c o u r i n g / survivor) 1.0  37.4 + 1 4 . 5  C  1.1  60.3  d  0.3  i 10.6  67  trials.  M o r t a l i t y was s i g n i f i c a n t l y h i g h e r (P = 0.05) on the 10 day  t r e a t m e n t compared t o the 21 day t r e a t m e n t .  However, 3 o u t o f 4 which  d i e d i n the 10 day t r e a t m e n t group d i d so w h i l e r e c e i v i n g b e f o r e 10 days o f age.  immunoglobulin  T h e r e f o r e , the r e s u l t i s s p u r i o u s .  o f p r o l o n g e d f e e d i n g o f immunoglobulin d e f i n i t e l y  The e f f e c t  reduced m o r t a l i t y by  m a i n t a i n i n g b e t t e r h e a l t h and p r e v e n t i n g s c o u r s i n t h o s e p i g s r e c e i v i n g immunoglobulin a f t e r 10 d a y s .  Death was due to b a c t e r i a l i n f e c t i o n c a u s i n g  d i a r r h e a i n 4 cases and pneumonia i n 1 c a s e .  S a l m o n e l l a was i s o l a t e d from  4 o f the 5 dead and presumed p r e s e n t a l s o i n the f i f t h . c a u s i n g death was d i a g n o s e d as S a l m o n e l l o s i s i n a l l  Thus the  cases.  infection  There was no  s i g n i f i c a n t d i f f e r e n c e between mean b i r t h w e i g h t s o f s u r v i v o r s and dead Pigs. Rate o f g a i n ( T a b l e 3 . 4 . b and F i g u r e 3 . 3 ) was h i g h e s t the group r e c e i v i n g immunoglobulins f o r 21 d a y s , but o n l y  in  significantly  h i g h e r (P = 0 . 0 5 ) than the group r e c e i v i n g immunoglobulins f o r 15 d a y s . The 21 day group had the h i g h e s t mean r a t e o f g a i n o f a l l groups i n  the  f o u r experiments c a r r i e d o u t . Frequency o f s c o u r i n g ( T a b l e 3 . 4 . b ) was v e r y markedly reduced d u r i n g t h i s t r i a l compared t o Experiment I I I recorded.  where i t was a l s o  The group r e c e i v i n g immunoglobulin f o r 21 days showed no  d i a r r h e a a f t e r 4 days o f age and t h e o t h e r two groups showed a much reduced f r e q u e n c y between 13 and 20 days o f age ( F i g u r e 3 . 2 ) . bowl f e e d i n g was e l i m i n a t e d and n i p p l e - f e e d i n g was c o n t i n u e d  Since throughout,  chances o f s p r e a d i n g c o n t a m i n a t i o n i n the f e e d were l i k e l y m a r k e d l y reduced. it  Water p r o v i s i o n was l i m i t e d t o p e r i o d i c b o t t l e f e e d i n g s i n c e  c o u l d n ' t be p r o v i d e d ad l i b i t u m w i t h o u t s p i l l i n g l e a d i n g to a wet  F i g u r e 3.3.  1400  Cumulative Weight Gain.  Experiment 4  f  1200  1000  A - 10 days on Immunoglobulin O - 15 days on Immunoglobulin • - 21 days on Immunoglobulin  800  600  400  200  11 Days of Age  13  15  69 environment which seemed to be deterimental to the pigs from experience i n the preceding t r i a l s .  70 3.6  General D i s c u s s i o n The approach o f t h i s s t u d y was t w o - f o l d .  ficial  Firstly,  r e a r i n g was seen as a mean f o r i n c r e a s i n g s u r v i v a l o f low  weight p i g s .  Secondly, this a r t i f i c i a l  artibirth-  r e a r i n g t e c h n i q u e w i t h immuno-  g l o b u l i n e x t r a c t was a p p l i e d i n a n o n - i s o l a t e d e n v i r o n m e n t .  T h u s , the  r e s u l t s can be d i s c u s s e d from both p e r s p e c t i v e s . An i m p o r t a n t o b s e r v a t i o n i n t h e s e t r i a l s was a l o w e r  rate  o f g a i n than p r e v i o u s l y found by McCallum (1977) u s i n g a v e r y s i m i l a r and by o t h e r workers ( F i g u r e 3 . 4 ) . treatment still  diet,  The r a t e was h i g h e s t w i t h the 21 day  i n E x p e r i m e n t IV where s c o u r i n g was m a r k e d l y reduced but was  w e l l below r a t e s found w i t h sow r e a r e d p i g s o f low b i r t h w e i g h t  within  the same herd (60g/day vs 1 2 5 g / d a y ) .  t h i s are e v i d e n t .  Two o u t s t a n d i n g reasons f o r  F i r s t l y , the p i g s on t r i a l  may have been r e s t r i c t e d  t h e i r f o o d i n t a k e t o o much f o r optimum g r o w t h . be a d e q u a t e , the main c o n t r i b u t i n g since their without  C o n s i d e r i n g the d i e t  f a c t o r c o u l d be too i n f r e q u e n t  i n t a k e a t each f e e d i n g was l i m i t e d by t h e i r c a p a c i t y .  a u t o m a t i c f e e d i n g , more f r e q u e n t f e e d i n g would be  in  to  feeding However,  difficult.  S e c o n d l y , the l o w e r r a t e o f g a i n may have been due t o t h e i r low b i r t h weights. Low b i r t h w e i g h t of g a i n .  seems t o have a d e f i n i t e e f f e c t on r a t e  However, Lodge and E l l i o t  (1979) i n d i c a t e d t h a t a l o w e r  w e i g h t was l e s s i n h i b i t i n g on growth under a r t i f i c i a l natural  rearing.  Widdowson ( 1 9 7 1 ) , i n a t r i a l ,  n e v e r r e a c h the p o t e n t i a l between low b i r t h w e i g h t and t r u e r u n t s .  Not a l l  r e a r i n g than under  showed t h a t r u n t p i g s  o f l a r g e l i t t e r mates.  p i g s which a r e normal  birth-  One must d i s t i n g u i s h  a n a t o m i c a l l y , but  p i g s under lOOOg a r e n e c e s s a r i l y r u n t s .  small, The  Figure  3.4  Comparative Growth Curves  A - Perry and Lecce A  -  »  "  (1968); a r t i f i c i a l  "  "  ; sow  rearing  o -: S i e r s e t a l . (1977); a r t i f i c i a l ; sow  rearing  rearing  rearing  O - T h i s t r i a l : Experiment IV (21 days on Ig)  10 Days of Age  12  14  16  18  20  22  72  m a n i f e s t a t i o n o f r u n t c h a r a c t e r i s t i c s i s l a r g e l y i n d i c a t e d by s i z e , however p i g s above 600g d o n ' t seem t o show any r u n t i n g a p p e a r a n c e . r u n t s seem u n d e r d e v e l o p e d , p o s s i b l y due to p r e n a t a l  True  undernourishment.  T h e i r p h y s i c a l appearance o f v e r y s m a l l s i z e and d i s p r o p o r t i o n a t e l y l a r g e domed heads s u g g e s t s t h i s .  S m a l l , but n o n - r u n t p i g s may n o t be as  d i s a d v a n t a g e d as t r u e r u n t s when p r o v i d e d adequate n u t r i t i o n and hence may show adequate compensatory growth t o make up f o r low Indeed, i n a l l However, a l l  but the f i r s t t r i a l , b i r t h w e i g h t  t h o s e below 500g a t b i r t h , d i e d .  birthweight.  d i d not a f f e c t It  survival.  i s p o s s i b l e t h a t the  s u r v i v a l o f v e r y s m a l l t r u e r u n t s ( e . g . below 500g b i r t h w e i g h t ) more e x t r a o r d i n a r y a t t e n t i o n  t o h y g i e n e and e n v i r o n m e n t .  D u r i n g s a m p l i n g o f the s o w - r e a r e d low b i r t h w e i g h t v a r i a b i l i t y on growth r a t e was found t o be h i g h ( c o e f f i c i e n t = 3 0 . 4 per c e n t ) .  requires  This i s understandable i f  of  pigs, variation  the o p e r a t i v e f a c t o r s  m i n i n g growth a t t h i s p r e - w e a n i n g age a r e c o n s i d e r e d .  deter-  Such f a c t o r s  include: 1.  N u r s i n g s u c c e s s which i s determined by a g g r e s s i v e n e s s , m i l k p r o d u c t i o n o f the sow, and a c c e s s t o a p r o d u c t i v e teat.  2.  Freedom from s c o u r s o r o t h e r d i s e a s e m a l a d i e s .  3.  Genetic potential  S i n c e low b i r t h w e i g h t  o f the  individual.  p i g s a r e l e s s c o m p e t i t i v e d u r i n g n u r s i n g and are more  s u s c e p t i b l e to c h i l l i n g (as e x p l a i n e d by the r e l a t i o n s h i p between w e i g h t , s u r f a c e a r e a , and h e a t l o s s ( M o n t e i t h and Mount, 1 9 7 4 ) ) ,  artificial  r e a r i n g i n a c o n t r o l l e d environment would e l i m i n a t e many o f the s t r e s s ful  f a c t o r s and a l l o w a more e q u i t a b l e s i t u a t i o n .  Runts may be even  73 f u r t h e r d i s a d v a n t a g e d f o r s u r v i v a l because o f a low r e s e r v e o f  carbohydrate  i n the l i v e r and muscles a t b i r t h f o r energy (Widdowson, 1 9 7 1 ) .  The h i g h  s u r v i v a l l e v e l s i n E x p e r i m e n t IV p r o v i d e s u p p o r t f o r the advantage o f artificial  r e a r i n g o f low b i r t h w e i g h t p i g s . The f a c t o r s c o n t r i b u t i n g  g l o b u l i n e x t r a c t can be a n a l y s e d .  t o the e f f i c a c y o f the immuno-  T h i s e x t r a c t , which i s a  " s a l t e d o u t " w i t h a 40 per c e n t ( N H ) 4  2  precipitate  SO^ s o l u t i o n , contains a l l of  the  gamma-globulin and much o f the b e t a - g l o b u l i n f r a c t i o n s o f serum (Owen, 1961). L i k e c o l o s t r u m , w h i c h i s c o n s i d e r e d a serum t r a n s u d a t e ( B o u r n e , 1 9 7 3 ) ,  it  would c o n t a i n o v e r 80 per c e n t I g G , l e s s IgA then c o l o s t r u m (8 vs 13 per c e n t ) , and more IgM t h a n c o l o s t r u m (10 vs 4 per c e n t )  (Bourne, 1973).  u n l i k e c o l o s t r u m , serum d e r i v e d immungolobulin c o n t a i n s no s e c r e t o r y (S-IgA).  IgA  One c o u l d presume t h a t the e f f i c a c y o f the e x t r a c t was predom-  i n a t e l y due t o IgG. cannot be i g n o r e d .  However, the p r e s e n c e o f IgM and n o n - s e c r e t o r y M i l e r e t a l _ . , (1975) found t h a t the minimum  concentrations for local protective  effect  i n l i g a t e d loop t e s t s with pigs  f o r e , even l o w e r l e v e l s o f IgM and IgA may have a s i g n i f i c a n t IgG i t s e l f , has been found to be o f s i g n i f i c a n t  e n t e r i c c o l i b a c i l l o s i s (Brandenburg and W i l s o n , 1 9 7 2 ) . w i t h i n the gut lumen i s open to q u e s t i o n but i t tinating properties  their  peristaltic  protective against  How IgG f u n c t i o n s  has a n t i t o x i n  ( B e n e c e r a f and Unanue, 1 9 7 9 ) .  There-  protection  and a g g l u -  A l t h o u g h i t may not be  a b l e t o adhere t o the gut l i n i n g as S - I g A d o e s , a g g l u t i n a t i o n would f a c i l i a t e  IgA  effective  were 0 . 5 , 0 . 0 5 , and 0.005 mg/ml o f I g G , IgM, and IgA r e s p e c t i v e l y .  effect.  Also,  of  bacteria  removal.  F i n a l l y , the e f f i c a c y of t h i s e x t r a c t a g a i n s t Salmonella bacteria i s of considerable interest.  To d a t e , t h i s t e c h n i q u e has been  74  used  to prevent m o r t a l i t y due  S c o o t , 1972;  McCallum, 1977;  t o E. c o l i and  enteritis  (Owen e_t aj_., 1961;  K e n e l l e y et_ a l _ . , 1979).  Since i t  p r o t e c t s a g a i n s t S a l m o n e l l a , as shown i n the p r e s e n t s t u d y , many o f the herds  from which the blood f o r immunoglobulin e x t r a c t i o n was  have a n t i g e n i c q u a n t i t i e s o f S a l m o n e l l a of  infesting  them.  these herds must have been g r e a t enough to p r o v i d e a  The  taken must contribution  sufficiently  high a n t i b o d y t i t r e a g a i n s t S a l m o n e l l a t o be p r e v e n t i v e i n these experiments.  75  Conclusions  1.  The a r t i f i c i a l  r e a r i n g technique with  artificial  immunoglobulins used i n t h e s e t r i a l s w i l l b i r t h w e i g h t p i g s i f weaned a t b i r t h .  save low  However, growth  r a t e i s r e s t r a i n e d , p o s s i b l y by r e s t r i c t i v e or 2.  by t h e i r low b i r t h  feeding  weight.  The l e v e l  o f immunoglobulin o f 10  the  day f o l l o w e d by 2 g/kg/day on s u c c e e d i n g days  first  g/kg./body weight on  seems to be e f f e c t i v e as a d o s i n g l e v e l . 3.  Longer p e r i o d s o f immunoglobulin a d m i n i s t r a t i o n may n e c e s s a r y i n a n o n - i s o l a t e d environment.  be  Whether t h i s  i s a r e s u l t o f low b i r t h w e i g h t i s not known. 4.  T h i s immunoglobulin  e x t r a c t used was  effective  protectio  a g a i n s t the S a l m o n e l l a b a c t e r i a encountered i n these trials.  C e r t a i n types o f S a l m o n e l l a may  endemic l e v e l s 5.  be p r e s e n t a t  i n many swine herds.  An i n c r e a s e d u n d e r s t a n d i n g o f the causes o f r u n t i n g i s n e c e s s a r y i n o r d e r to j u s t i f y the e f f o r t o f a t t e m p t i n g to  save the s m a l l e s t  ones.  76 Foot-Notes 1.  R and H Farms, A l d e r g r o v e , B . C .  2.  Federated Cooperatives L t d . ( f o r p i g s and l a m b s ) .  3.  Furoxone i s manufactured by t h e A u s t i n Company, C l e v e l a n d , Ohio. I t c o n t a i n s the a c t i v e i n g r e d i e n t f u r a z o l i d o n e , a n i t r o f u r a n , and i t i s a broad s p e c t r u m , s y n t h e t i c a n t i b a c t e r i a l compound.  4.  A n i s t a t i s a broad spectrum a n t i b i o t i c c o n t a i n i n g C h l o r a m p h e n i c a l , Neomycin S u l f a t e , S u l f a t h i a z o l e , and S u l f a m e t h a z i n e . The m a n u f a c t u r e r i s not known.  \  Milk Replacer - 30.  77 BIBLIOGRAPHY A l l e n , W.D. and P o r t e r , P. 1973. The r e l a t i v e d i s t r i b u t i o n o f IgM and IgA c e l l s i n i n t e s t i n a l mucosa and lymphoid t i s s u e s o f the young unweaned p i g and t h e i r s i g n i f i c a n c e i n o n t o g e n e s i s o f s e c r e t o r y immunity. B a c h , J . F . 1976. A n t i g e n and A n t i b o d y R e a c t i o n s ; p p . 2 4 8 - 2 8 8 , i n "Immunology", e d i t e d by B a c h , J . F . , John W i l e t and S o n s , Toronto. B e n e c e r a f , B. and Unanue, E . R . 1979. Textbook b f Immunology; and W i l k i n s , B a l t i m o r e and London. B e r e s k i n , B . ; S h e l b y , C . E . ; and C o x , D . F . 1973. Some f a c t o r s pig s u r v i v a l . J . of An. Sc. 36:821-827.  Williams  affecting  B i e n e n s t o c k , J . 1979. The P h y s i o l o g y o f the L o c a l Immune Response; p.3 i n "Immunology o f the G a s t r o i n t e s t i n a l T r a c t " e d i t e d by A s q u i t h , P . , C h u r c h i l l L i v i n g s t o n e , N.Y. B i n n s , R.M. 1967. Bone marrow and lymphoid c e l l i n j e c t i o n o f the p i g f e t u s r e s u l t i n g i n t r a n s p l a n t a t i o n t o l e r a n c e o f immunity and immunoglobulin p r o d u c t i o n . Nature (London) 214: 179-181 B i n n s , R.M. 1973. C e l l u l a r Immunology i n the P i g . 6 6 : 1155-1160.  P r o c . R. S o c . Med.  B i n n s , R.M. and Symons, D . B . A . 1974. The Ontogeny o f Lymphocyte Immunog l o b u l i n D e t r i m e n t s and t h e i r R e l a t i o n s h i p t o A n t i b o d y P r o d u c t i o n i n the F e t a l P i g . R e s . i n V e t . S c . 16: 260-262 B l e c h a , F. and K e l l e y , K.W. 1981. C o l d S t r e s s Reduces the A q u i s i t i o n o f C o l o s t r a l Immunoglobulin i n P i g l e t s . J . A n . S c . 52:594-600 B o u r n e , F . J . 1973. The Immunoglobulin System o f the S u c k l i n g P i g . Proc. Nutr. Soc. 32:205-215. B o u r n e , F . J . and C u r t i s , J . 1973. The T r a n s f e r o f Immunoglobulins I g G , IgA and IgM from Serum t o C o l o s t r u m and M i l k i n the Sow. Immunol. 2 4 : 1 5 7 - 1 6 2 . B o w l a n d , J . P . 1966. Swine M i l k C o m p o s i t i o n - A Summary; i n "Swine i n B i o M e d i c a l R e s e a r c h " ; pp. 97 - 108 e d i t e d by B u s t a d , L . K . and M c C l e l l a n , R . O . ; B a t e l l e Memorial I n s t i t u t e , R i c h l a n d , U . S . A . B r a n c h e , W . ; Young, V ; R o b i n e t , H . ; and M a s s e y , E. 1963. The E f f e c t o f C o l i c i n e P r o d u c t i o n on E. c o l i i n the Normal Human I n t e s t i n e . P r o c . o f the S o c . o f E x p ' t ' l B i o l , and Med. 114:198. B r a n d e n b u r g , A . C . and W i l s o n , M.R. 1972. Immunity t o E. c o l i i n P i g s : IgG Immunoglobulin i n P a s s i v e Immunity t o E . c o l i E n t e r i t i s . Immunology 2 4 : 1 1 9 .  78  Brandenburg, A.C. and W i l s o n , M.R. 1974. Immunity t o E. c o l i i n p i g s : IgE and Blood C l e a r a n c e . Res. i n Vet. Sc. 16:171-175. Brandtzaeg,  P. 1973. S t r u c t u r e , Syntheses and E x t e r n a l T r a n s f e r o f Mucosal Immunoglobulins. Ann. Immunol ( I n s t . P a s t e u r ) 124C: 417-438.  Brandtzaeg,  P. and B a k l i e n , K. 1977. I n t e s t i n a l S e c r e t i o n o f IgA and IgM: a H y p o t h e t i c a l Model, pp. 77-144 i n Immunology o f f i b a Foundation Sypposium 46 E l s e v i e r , E x c e r p t a Medica, North H o l l a n d , N.Y.  Brandtzaeg,  P. and S w i l a h t i , E. 1976. F u r t h e r Evidence f o r a Role o f S e c r e t o r y Component (S.C.) and o f J c h a i n i n the G l a n d u l a r T r a n s p o r t o f IgA, pp. 219-226 i n " S e c r e t o r y Immunity and I n f e c t i o n " , e d i t e d by McGhee, J . R., Mestecky, J . , and B a l b , J . L..; Plenum P r e s s , N.Y. 1978.  Brambell,  F.W. Rogers. 1970. The T r a n s m i s s i o n o f P a s s i v e Immunity from Mother t o Young. North-rHolland P u b l i s h i n g Co., London.  Brown, P . J . and Bourne, F . J . 1976. Development o f Immunoglobulinc o n t a i n i n g C e l l P o p u l a t i o n s i n I n t e s t i n e , Spleen and M e s e n t e r i c Lymph Nodes o f t h e Young P i g , as Demonstrated by P e r o x i d a s e conjugated Antiserum. Ann. J . V e t . Res. 37:1309-1314. B u l l e n , J . J . i Rogers, H.J.; L e i g h , L. 1972. I r o n - b i n d i n g P r o t e i n s i n M i l k and R e s i s t a n c e t o E. c o l i I n f e c t i o n i n I n f a n t s . B r i t . Med. J . 1:69-73. Carroll,  W.E.; K r i d e r , J . L . ; and Andrews, F.N. 1962. Swine P r o d u c t i o n 3rd E d i t i o n p.137. McGraw-Hill Book Co. N.Y.  Chidlow, J.W. and P o r t e r , P. 1979. I n t e s t i n a l Defense o f the Neonatal Pig. I n t e r r e l a t i o n s h i p o f Gut and Mammary F u n c t i o n P r o v i d i n g S u r f a c e Immunity A g a i n s t C o l i b a c i l l o s i s . V e t . Rec. 10^:^96-500. C h r i s t e n s e n , J . ; Weisbrodt, N.; and Hansen, R. 1972. E l e c t r i c a l Wave o f t h e Proximal Colon o f the Cat i n D i a r r h e a . G a s t r o e n t e r o l o g y 62:1167-1168.  Slow  C o a l s o n , J.A. and Lecce, J.G. 1973. Herd D i f f e r e n c e s i n t h e E x p r e s s i o n o f F a t a l D i a r r h e a i n A r t i f i c i a l l y Reared P i g l e t s Weaned A f t e r 12 hours v s . 36 hours o f N u r s i n g . J . An. Sc. 36:11141121. C o a l s o n , J.A. and L e c c e , J.G. 1973. I n f l u e n c e o f Nursing I n t e r v a l s on Changes i n Serum P r o t e i n (immunoglobulins) i n Neonatal P i g s . J . An. Sc. 36:381-385.  C o l t e n , H.R. 1977. "Development o f Host Defense: t h e Complement and P r o p e r d i n Systems", i n Development o f Host Defenses; e d i t o r s Cooper, M.D. and Dayton D.H. , Raven P r e s s , N.Y. Cooper, M.D. and Lawton, A.R. 1974. "The Development o f t h e Immune System", i n Readings from the S c i e n t i f i c American: "Immunology"; W.H. Freeman and Co., San F r a n c i s c o , 1976. Cooper, J . E . ; John, V.; McFayden, I.R.; and Wooten, R. 1978. E a r l y Appearance o f Pointing i n P i g l e t s . V e t . Rec. 102:529. C r a i g , S.W.  and Cebra, J . J . 1971. Peyer's Patches - an E n r i c h e d Source o f P r e c u r s o r s o f IgA Producing Immunocytes i n t h e Rabbit. J . o f E x p t ' l . Med. 134:188-200.  C r a n w e l l , P.O.; Noakes, D.E.; and H i l l , K.J. 1968. the Stomach Content o f t h e S u c k l i n g Pi a. 27:26A.  Observations o f P r o c . Nutr. Soc.  C r a n w e l l , P.D. and T i t c h e n , D.A. 1974. G a s t r i c A c i d S e c r e t i o n i n Newly Born P i g l e t s . Res i n V e t . Sc. 16:105-107. C u r t i s , J . and Bourne, F . J . 1971. Immunoglobulin Q u a n t i t a t i o n on Sow Serum, C o l o s t r u m , and M i l k i n t h e Serum o f Young P i g s . Biochim Biophys A c t a 236:319-332. C u r t i s , S.E. 1974. P i g Barn Environment: How I t A f f e c t s Baby P i g Performance. Canadian Pork, Feb. 1974, p.9. Day, N.K.B.; P i c k e r i n g , R.J.; Gewarz, H.; and Good, R.A. 1969. Ontoaem'c Development o f t h e Complement System. Imm. 16:319-322. Dixon, F . J . ; J a c o t - G u i l l a r m o d , H.; and McConahey, P.J. 1967. The E f f e c t o f P a s s i v e l y A d m i n i s t e r e d Antibody on Antibody Synthesis. J . o f E x p t ' l Med. 125:1119-1121. Dixon, J.M. and P a u l l e y , J.W. 1963. The B a c t e r i o l o g i c a l and H i s t o l o g i c a l S t u d i e s o f t h e Small I n t e s t i n e o f Rats T r e a t e d with Mecamylamine. Gut 4:169-172. Dupont, H.L. and P i c k e r i n g , L.K. 1980. O b s e r v a t i o n s on t h e Pathogen P r o p e r t i e s o f the K88, HLY, and E n t . Plasmids o f E. c o l i w i t h P a r t i c u l a r Reference t o P o r c i n e D i a r r h e a . J . Med. Microb. 4:467-469. Edwards, B.L. 1972. 249-258.  Causes o f Death i n New-born P i g s .  V e t . B u l l . 42  80  E l l i o t , J . I . ; L o d g e , G . A . ; and H a r t s o c k , T . G . 1978. Practical A r t i f i c i a l R e a r i n g o f Neonatal P i g l e t s under Noni s o l a t e d C o n d i t i o n s . Can. J . An. S c . 58:799-800. E n g l a n d , D . C . 1974. Husbandry Components i n P r e n a t a l and P e r i n a t a l Development i n S w i n e . J . o f A n . S c . 3 8 : 1 0 4 5 - 1 0 4 9 . E n g l i s h , P . R . and S m i t h , W . J . 1975. Some Causes o f Death i n Neonatal Piglets. V e t . Annual 1 5 : 9 5 - 1 0 4 . Fahmy, M.H. and B e r n a r d , C. 1971. Causes o f M o r t a l i t y i n Y o r k s h i r e P i g s from B i r t h t o 20 Weeks o f A g e . Can J . A n . S c . 5 1 : 351-359. F r e t e r , R. 1974. I n t e r a c t i o n s Between Mechanisms C o n t r o l l i n g the Intestinal Microflora. Amer. J . o f C l i n . N u t r . 27:1409-1411 F r e t e r , R. and Abrams, G. 1972. F u n c t i o n o f V a r i o u s I n t e s t i n a l B a c t e r i a i n C o n v e r t i n g G e r m - f r e e M i c e t o Normal S t a t e . I n f e c t . Imm. 6 : 1 1 9 - 1 2 1 . G e a r h a r t , P . J . ; J o h n s o n , N . D . ; Douglas R . ; and Hood, L. 1981. IgG A n t i b o d i e s t o P h o s p h o r y l c h o l i n e E x h i b i t More D i v e r s i t y than T h e i r IgM C o u n t e r p a r t s . Nature 2 9 1 : 2 9 - 3 4 . G i a n e l l a , R . A . ; B r o i t m a n , S . A . ; and Z i n c h e k , N. 1971. S a l m o n e l l a Enteritis: I. R o l e o f Reduced G a s t r i c S e c r e t i o n i n P a t h o g e n e s i s . Amer. J . D i g . D i s . 1 6 : 1 0 0 0 - 1 0 1 0 . Gyles, C.L.  1971. H e a t - l a b i l e and H e a t - s t a b l e Forms o f the E n t e r o t o x i n from E . c o l i S t r a i n s E n t e r o p a t h o g e n i c f o r P i g s . A n n . N . Y . Academy S c . 1 7 6 : 3 1 4 - 3 2 2 .  H a s l a n d , A . J . ; M o n i e , H . J . ; and Gowans, J . L . 1977. The N a t u r a l H i s t o r y o f the C e l l s P r o d u c i n g IgA i n the G u t . p.29 i n "Immunology o f the G u t " . C i b a F o u n d a t i o n 4 6 , E l s e v i e r , Excerpta Medica, North H o l l a n d , N.Y. Haye, S . N . and K o r n e g a y , E . T . 1979. Immunoglobulin G , A , and M and A n t i b o d y Response i n Sow-reared and A r t i f i c i a l l y Reared Pigs. J . An. S c . 48:1116-1122. H i l l , K.J.  1970. Development and Comparative A s p e c t s o f D i g e s t i o n . i n "Dukes P h y s i o l o g y " , 8 t h E d i t i o n Swenson, M . J . e d i t o r , Cornell Univ. P r e s s , N.Y.  Hill,  and P o r t e r , P. 1974. S t u d i e s o f B a c t e r i c i d a l A c t i v i t y t o E . c o l i o f P o r c i n e Serum and C o l o s t r a l Immunoglobulins and the R o l e o f Lysozyme w i t h S e c r e t o r y IgA. Imm. 2 6 : 1239-1250.  I.R.  81  Hood, L.E.; Weissman, I.L.; and Wood, W.B. 1978. Immunology. Benjamin/Cummings P u b l i s h i n g C. I n c . , Don M i l l s , Ont. Hughes, J.M. ; Hurad, F.; and Chang, B. 1978. Role o f C y c l i c AMP i n the A c t i o n o f H e a t - s t a b l e E n t e r o t o x i n o f E. c o l i . Nature 271:755-756. J o n e s , A.S.  1972. Problems Weaned P i g l e t s . 19-32.  o f N u t r i t i o n and Management o f E a r l y Proceedings o f the B r i t . Soc. o f An. Prod.  K e n n e l l y , J . J . ; B a l l , R.O.; and Aherne, F.X. 1979. Influence of P o r c i n e Immunoglobulin A d m i n i s t r a t i o n on S u r v i v a l and Growth o f P i g s Weaned a t 2 and 3 Weeks o f Age. Can. J . An. Sc. 59:693-698. Kenworthy, R. 1970. E f f e c t o f E. c o l i on Germ-free and G n o t o b i o t i c Pigs. I. L i g h t and E l e c t r o n M i c r o s c o p y o f the Small Intestine. J . o f Comp. Path. 70:53-63*.  Kim, Y.B.;  B r a d l e y , S.G.; and Watson, D.W. 1966. Antibody Synthesis w i t h Germ-free C o l o s t r u m - d e p r i v e d M i n i a t u r e P i g l e t s , in "Swine i n B i o m e d i c a l Research", e d i t e d by Bustad, L.K. and M c C l e l l a n , R.D., B a t e l l e Memorial I n s t i t u t e , R i c h l a n d , Wash.  Kim,  B r a d l e y , G.; and Watson, D. 1967. Ontogeny o f the Immune Response. IV. Role o f A n t i g e n E l i m i n a t i o n i n the True Primary Immune Response i n Germ-free Colostrumdeprived P i g l e t s . J . Immunology 99:320-325.  Y.B.;  Klinman, N.R. and P r e s s , J . L . 1975. The C h a r a c t e r i z a t i o n o f the B C e l l R e p e r t o i r e S p e c i f i c f o r 2 , 4 - D i n i t r o p h e n y l and 2 , 4 , 6 - T r i n i t r o p h e n v l Determinants i n neonatal BALB/c Mice. J . E x p t ' l Med. 141:1132-1134. Knop, J . ;  Bren, H.; Wernet, D.; and Rowley, D. 1971. The R e l a t i v e A n t i b a c t e r i a l E f f i c i e n c y o f IgM, IgG, and IgA from P i g Colostrum. A u s t r . J . o f Exp. B i o l and Med. Sc. 49:405-^08.  K o h l e r , E.M. 1972. P a t h o g e n e s i s o f Neonatal E n t e r i c in Pigs. J.A.V.M.A. 160:574-582.  Collibacillosis  Kruml, J . ; Kovann, F.; P o s p i s i l , M.; and T r e b i c h a v s k y , I. 1970. The Development o f Lymphatic T i s s u e During Ontogeny, pp. 35-54 i n "Developmental A s p e c t s o f A n t i b o d y Formation and Structure", V o l . I . e d i t e d by S t e r z l , J . and R i h a , I . , Academic P r e s s , N.Y.  82  Lai  A F a t , ; M c C l e l l a n d , D.B.L.; and Van F u r t h , R. 1976. In V i t r o S y n t h e s i s o f Immunoglobulins, S e c r e t o r y Component, Complement, and Lysozyme by Human G a s t r o - i n t e s t i n a l Tissues. I . Normal T i s s u e s . C l i n . Exp. Imm. 23:9-19.  Lamm, M.E.;  W e i s z - C a r r i n g t o n , P.; Roux, M.E.; McWilliams, M.; and P h i l l i p s - Q u a g l i a t a , J.M.. 1978. Development o f the IgA System and the Mammary Gland, pp. 35-42 i n " S e c r e t o r y Immunity and I n f e c t i o n " , e d i t e d by McGhee, J.R.; Mestecky, J . ; and Babb, J . L . Plenum P r e s s , N.Y.  L a s k o w s k i , M.; K a s s e l l , B.; and Hagerty, G. 1957. A Crystalline T r y p s i n I n h i b i t o r from Swine Colostrum. Biochim. B i o p h y s i c a A c t a 24:300-305. L e c c e , J.G.  1969. Rearing C o l o s t r u m - f r e e P i g s i n an Feeding D e v i c e . J . An Sc. 28:27-33.  Automatic  L e c c e , J.G.  1971. R e a r i n g Neonatal P i g l e t s o f Low B i r t h - w e i g h t w i t h an Automatic Feeding D e v i c e . J . An. Sc. 33:47-51.  L e c c e , J.G.  1975. R e a r i n g P i g l e t s A r t i f i c i a l l y i n a Farm E n v i r o n ment: a Promise U n f u l f i l l e d . J . An. Sc. 41:659-666.  Lodge, G.A.  and E l l i o t , J . I . 1979. The I n f l u e n c e o f B i r t h - w e i g h t on the Subsequent Growth o f Hysterectomy-derived P i g s . Can J . An. Sc. 59:215-216.  Lucas, I.A.M. and Lodge, G.E. 1961. The N u t r i t i o n o f the Young P i g : A Review. Tech. Communication o f the Commonwealth Bureau o f Animal N u t r i t i o n #22, Rowett I n s t i t u t e , Aberdeen, Scotland. Manners, M.J. 1976. The Development o f D i g e s t i v e F u n c t i o n i n the P i g , from "A Symposium i n Q u a n t i t a t i v e A s p e c t s o f P i g N u t r i t i o n " . . Proc. o f Nutr. Soc. 35:49-56. M a r r a b l e , A.W. 1971. The Embryonic P i g : a C h r o n o l o g i c a l Account. Pitman M e d i c a l . Mayer, M.M.  1973. The Complement System, pp. 143-157 i n "Readings from S c i e n t i f i c American, "Immunology"". W.H. Freeman and Co. San F r a n c i s c o .  McCallum, I.M. 1977. Saskatoon.  Masters T h e s i s .  U n i v e r s i t y o f Sask.,  83  M c C a l l u m , I . M . ; E l l i o t , J . I . ; and Owen, B . D . 1977. S u r v i v a l o f C o l o s t r u m - d e p r i v e d Neonatal P i g l e t s Fed G a m m a - g l o b u l i n s . Can. J . A n . S c . 5 7 : 1 5 1 - 1 5 8 . M c C l e l l a n d , D . B . L . 1979. B a c t e r i a l and V i r a l I n f e c t i o n s o f t h e Gastro-intestinal Tract, p p . 214-245 i n "Immunology o f the G a s t r o - i n t e s t i n a l T r a c t . " E d i t e d by A s q u i t h , P . , C h u r c h i l l L i v i n g s t o n e , N.Y. M i l e r , I.;  C e r n a , J . ; T r a v n i c e k , J . ; R e j n e k , J . ; and K r u m l , J . 1975. The R o l e o f Immune P i g C o l o s t r u m , Serum and Immunoglobulins I g G , IgM, and IgA i n L o c a l I n t e s t i n a l Immunity A g a i n s t E n t e r o t o x i c S t r a i n s o f E. c o l i 055 i n Germ-free P i g l e t s . F o l i a Microb. 20:433-438.  M o n t e i t h , J . L . and Mount, L . E . , e d i t o r s o f "Heat L o s s from A n i m a l s and M a n " , B u t t e r w o r t h s , London, 1974. N e w l a n d , H.W.; M c M i l l a n , W . M . ; and R e i n e k e , E . P . 1952. Temperature A d a p t a t i o n i n the Baby P i g . J . A n . S c . 1 1 : 1 1 8 - 1 3 3 . N i e l s e n , N . O . ; Moon, H.W.; and R o e , W.E. 1968. E n t e r i c C o l l i b a c i l l o s i s i n S w i n e . J . A . V . M . A . 153:1590-1606. Oram, J . D . and R e i t e r , B. 1968. I n h i b i t i o n o f B a c t e r i a by L a c t o f e r r i n and o t h e r I r o n - c h e l a t i n g A g e n t s . Biochimi et Biophysica Acta 170:351-353. Owen, B . D .  1961. E f f e c t s o f P o r c i n e Immune G l o b u l i n A d m i n i s t r a t i o n on the S u r v i v a l and Serum P r o t e i n C o m p o s i t i o n o f C o l o s t r u m - d e p r i v e d P i g s Reared i n a N a t u r a l E n v i r o n m e n t . Phd T h e s i s , Univ. of S a s k . , Saskatoon.  Owen, B.D. and B e l l , J . M . 1964. F u r t h e r S t u d i e s o f S u r v i v a l and Serum P r o t e i n C o m p o s i t i o n i n C o l o s t r u m - d e p r i v e d P i g s Reared i n a N o n - i s o l a t e d E n v i r o n m e n t . Can. J . An. Sc. 44:1-7. Owen, B . D . ; B e l l , J . M . ; W i l l i a m s , C M . ; and O a k e s , P . G . 1961. E f f e c t s o f P o r c i n e Immunoglobulin A d m i n i s t r a t i o n on the S u r v i v a l and Serum P r o t e i n C o m p o s i t i o n o f C o l o s t r u m d e p r i v e d P i g l e t s Reared i n a N o n - i s o l a t e d E n v i r o n m e n t . Can. J . A n . S c . 4 1 : 2 3 6 - 2 5 2 .  84  Ozawa, A. and F r e t e r , R. 1964. E c o l o g i c a l Mechanisms C o n t r o l l i n g Growth o f E. c o l i i n Continuous Flow C u l t u r e s and t h e Mouse I n t e s t i n e . J . I n f e c t . D i s . 114:235 Parmely, M.J. and Beer, A.E. 1977. C o l o s t r a l C e l l - m e d i a t e d Immunity and t h e Concept o f a Common S e c r e t o r y Immune System. J . D a i r y Sc. 60:655-665. Parmely, M.J.; Beer, A.E.; and B i l l i n g h a m , R.E. 1976. In V i t o S t u d i e s on t h e T-Lymphocyte P o p u l a t i o n o f Human M i l k . J . E x p t ' l Med. 144:358-370. Payne, L.C. and Marsh, C L . 1962. Gamma-globulin A b s o r p t i o n i n t h e Baby P i g : The N o n - s e l e c t i v e A b s o r p t i o n o f Heterologous G l o b u l i n s and F a c t o r s I n f l u e n c i n g A b s o r p t i o n Time. J . N u t r i t i o n 76:151-158. P e r r y , G.C. and L e c c e , S.G. 1968. The Rearing o f Colostrum Deprived P i g l e t s . An. Prod. 10:433-444. P e r r y , J . S . and Rowe 11, J.G. 1969. V a r i a t i o n s i n F e t a l Weight and V a s c u l a r Supply Along t h e U t e r i n e Horn o f t h e P i g . J . o f Reprod. and F e r t . 19:527-530. Pestana,  C ; S h o r t e r , R.G.; and H a l l e n b e c k , J . o f S u r g i c a l Res. 5:471.  G.A.  1965.  P i e r c e , N.F. and Gowans, J . L . 1975. C e l l u l a r K i n e t i c s o f the I n t e s t i n a l Immune Response t o C h o l e r a Toxoid i n R a t s . J . o f E x p t ' l . Med. 142:1550-1563. Pomeroy, R.W. 1960. I n f e r t i l i t y and Neonatal M o r t a l i t y i n t h e Sow. III. Neonatal M o r t a l i t y and F e t a l Development. J . Ag. Sc. 54:31-56. P o r t e r , P.  1976. I n t e s t i n a l A b s o r p t i o n o f C o l o s t r a l IgA A n t i E. c o l i A n t i b o d i e s by t h e Neonatal P i g l e t and C a l f , pp. 397-408 i n " M a t e r n o f o e t a l T r a n s m i s s i o n o f Immunoglobulins". The Proceedings o f a Symposium on T r a n s m i s s i o n o f Immunoglobulins from Mother t o Young, e d i t e d by Hemmings, W.A.; Cambridge Univ. P r e s s , N.Y.  P o r t e r , P.  1979. Immunobiology o f the A l i m e n t a r y T r a c t i n R e l a t i o n to Oral Immuno-prophylaxis A g a i n s t E n t e r i c I n f e c t i o n s i n the P i g l e t and C a l f . pp.268-287 i n "Immunology o f t h e G a s t r o - i n t e s t i n a l T r a c t " , e d i t e d by A s q u i t h , P., C h u r c h i l l L i v i n g s t o n e , N.Y.  85  P o r t e r , P. and A l l e n , W.D. 1972. C l a s s e s o f Immunoglobulin R e l a t e d to Immunity i n t h e P i g . J.A.V.M.A. 160:511-518. P o r t e r , P.; Noakes, D.E.; and A l l e n , W.D. 1972. of Immunoglobulins i n t h e Pre-ruminant Imm. 23:299-312.  Intestinal Secretion Calf.  P o r t e r , P.; P a r r y , S.H.; and A l l e n , W.D. 1977. S i g n i f i c a n c e o f Immune Mechanisms i n r e l a t i o n t o E n t e r i c I n f e c t i o n s o f t h e G a s t r o - i n t e s t i n a l T r a c t i n Animals", p.55 i n "Immunology o f t h e Gut", C i b a Foundation Symposium 46, E l s e v i e r , E x c e r p t a Medica, North H o l l a n d N.Y. P o w e l l , D.; P l o t k i n , G.; Maenza, R.; Sol b e r g , L . ; C u t l i n , D.; and Formal, S. 1971. Experimental D i a r r h e a . I . I n t e s t i n a l Water and E l e c t r o l y t e T r a n s p o r t i n Rat S a l m o n e l l a Enterocolitis. G a s t r o e n t e r o l o g y 60:1053-1060. Prokesova,  L.; Rejnek, J . ; S t e r z l , J . ; T r a v n i c e k , J . 1970. O n t o g e n e t i c Development o f Immunoglobulins i n P i g s , pp. 757-766 i n "Developmental A s p e c t s o f A n t i b o d y Formation and S t r u c t u r e " . V o l . I I , e d i t e d by S t e r z l , J . and R i h a , I . , Academic P r e s s , N.Y.  R o d e f f e r , H.E.; Leman, A.D.; and M u e l l e r , A.E. 1975. Development of a Record System f o r Measuring Swine B r e e d i n g Herd Efficiency. J . An. Sc. 40:13-18. Rowley, D.  and T u r n e r , K.J. 1966. Number o f M o l e c u l e s o f A n t i b o d y Required t o Promote P h a g o c y t o s i s by One Bacterium. Nature, (London) 210:496-498.  R u t t e r , J.M. 1975. E. c o l i I n f e c t i o n i n P i g l e t s : P a t h o g e n e s i s , V i r u l e n c e , and V a c c i n a t i o n . V e t . Rec. 96:171-175. R u t t e r , J.M.; J o n e s , G.W.; Brown, G.T.H.; Burrows, M.R.; and L u t h e r , P.D. A n t i b a c t e r i a l A c t i v i t y i n Colostrum and M i l k Associated with Protection o f P i g l e t s Against E n t e r i c D i s e a s e Caused by K 8 8 - P o s i t i v e E. c o l i . I n f e c t . Imm. 13:667-676 S c o o t , A.  1973. Pigs.  Feeding Immunoglobulin t o Colostrum Deprived Masters T h e s i s , Univ. o f Sask., Saskatoon.  S e a r l e , S.R. 1971. T o p i c s i n V a r i a n c e Component E s t i m a t i o n . B i o m e t r i c s 27:1-76.  86  Segre, D.  1966. Swine i n Immunological Research, pp.269-272 i n "Swine i n B i o m e d i c a l Research", e d i t e d by Bustad, L.K. and M c C l e l l a n , R.D., B a t t e l l e Memorial I n s t i t u t e , R i c h l a n d , Wash.  S e g r e , D. and Myers, W.L. 1964. Antibody P r o d u c t i o n i n Baby P i g s . Amer. J . V e t . Res. 25:413-419. S e i r s , D.G.; D a n i e l s o n , D.M.: C h a i , E.T.; and K e a s l i n g , H.H. 1977. Late G e s t a t i o n Feeding o f D i c h l o r v o s : The Response o f A r t i f i a l l y and Dam-reared L i t t e r s . J.An. Sc. 44:1-7. Sharpe, H.B.A. 1966 Preweaning M o r t a l i t y i n a Herd o f Large White Pigs. B r i t . Vet. J . 122:99-111. S h e d l o f s k y , S. and F r e t e r , R. Synergism Between E n l o g i c and Immunol o g i c C o n t r o l Mechanism o f I n t e s t i n a l F l o r a . J . I n f e c t . D i s . 129:296-301. S i l v e r s t e i n , A.M. 1977. Ontgeny o f t h e Immune Response: A Perspective; i n "Development o f Host Defenses", e d i t e d by Cooper, M.D. and Dayton, D.H., Raven P r e s s , N.Y. Smith, H.W.  Snedecor,  and Linggood, M.A. 1971. O b s e r v a t i o n s on t h e Patho g e n i c P r o p e r t i e s o f t h e K88, HLY and E n t . Plasmids o f E. c o l i w i t h P a r t i c u l a r Reference t o P o r c i n e D i a r r h e a . J . Med. M i c r o b . 4:^67-470.  G.W. 6th  and Cochran, W.G. 1967. S t a t i s t i c a l E d i t i o n , Iowa S t a t e Univ. P r e s s .  Solomon, J.B. 1971. F o e t a l and Neonatal P u b l i s h i n g Co., London. S p r i n z , H.  1969. Pathogenesis o f I n t e s t i n a l Arch P a t h o l . 87:556-558.  S t e e l e , E . J . ; Chaicumpa, W.; Rowley, D. Sterzl, J.  Immunology.  Methods.  North-Holland  Infections.  1974. J . I n f . D i s . 130:93-95.  1963. A n t i b o d y Formation by C e l l s I s o l a t e d from Donors o f D i f f e r e n t Ages A f t e r T r a n s f e r t o Young R a b b i t s and t o X - i r r a d i a t e d A d u l t R a b b i t s . F o l i a M i c r o b . 8:69-72.  S t e r z l , J . ; Kostka, J . ; Pesak, V.; and J i l e k , M. 1964. The R e l a t i o n Between B a c t e r i c i d a l A c t i v i t y o f Complement and the C h a r a c t e r o f the B a c t e r i a l S u r f a c e s . F o l i a M i c r o b . 9:284-286.  87 S t e r z l , J . ; V e s e l y , J . ; J i l e k , M.; and Mandel, L. 1965. The I n d u c t i v e Phase o f A n t i b o d y Formation S t u d i e d w i t h Isolated C e l l s , p.^63 i n " M o l e c u l a r and C e l l u l a r B a s i s o f A n t i b o d y F o r m a t i o n " , e d i t e d by S t e r z l , J . , Pub. House o f Czeck Acad. Sc., Prague. Tennant,  B.C. and Hornbuckle, W.E. 1980. Gastro-intestinal Function, i n " C l i n i c a l B i o c h e m i s t r y o f Domestic Animals", 3rd E d i t i o n , e d i t e d by Kaneko, J . J . , Academic P r e s s , T o r o n t o , Ont..  T l a s k a l o v a , H.; S t e r z l , J . Hajek, P.; P o s p i s i l , M; R i h a , I . ; Marvanova, H.; Kamarytova, V.; Mandel, L.: Kruml, J . ; and Kovaru, F. 1970. The Development o f A n t i b o d y Formation During Embryonal and P o s t n a t a l P e r i o d s , i n "Developmental A s p e c t s o f A n t i b o d y Formation and S t r u c t u r e " , V o l . I I , e d i t e d by S t e r z l , J . and R i h a , - I . , Academic P r e s s , N.Y. Tomasi, T.B. 1976. The Immune System o f S e c r e t i o n s . I n c . , N.J., N.Y.  Prentice-Hall  Tomasi, T.B. and C a l v a n i c o . 1968. Human S e c r e t o r y Gamma-A. Fed. P r o c . 27:617 ( a b s t r ) . Tonegawa, S.; Maxim, A.M.; T i z a r d , R.; Bernard, 0.; and G i l b e r t , 1978. Sequence o f a Mouse Germ-line Gene f o V a r i a b l e Region o f an Immunoglobulin L i g h t C h a i n . Proc. N a t ' l . Acad. Sc., U.S.A. 75:1485-1499.  W.  I ' l l r e y , D.E.; Long, C.H.; and M i l l e r , E.R. 1966. Absorption of I n t a c t P r o t e i n from the I n t e s t i n a l Lumen o f the Neonatal Pig. pp.249-262 i n "Swine i n B i o m e d i c a l Research" e d i t e d by Bustad, L.K. and M c C l e l l a n , R.O., Battelle Memorial I n s t i t u t e , R i c h l a n d Wash. Waldorf, D.P.; F o o t e , W.C.; S e l f , H.L.; Chapman, A.B.; and C a s i d a , L.E. 1957. F a c t o r s A f f e c t i n g F e t a l P i g Weight L a t e i n Gestation. J . An. Sc. 16:976-985. Walker, W.A.  1979. G a s t r o - i n t e s t i n a l Host Defense: Importance o f Gut C l o s u r e i n C o n t r o l o f Macromolecular T r a n s p o r t , i n "Development o f Mammalian A b s o r p t i v e P r o c e s s " , C i b a F o u n d a t i o n Symposium, E l s e v i e r , E x c e r p t a Medica, North H o l l a n d , N.Y.  Weide, K.;  Sanger, V.; and Lagace, A. 1962. Innoculation of Baby P i g s w i t h Hog C h o l e r a V a c c i n e . A.J.V.M.A. 141:464-469.  88 W h i t e , F . ; Wenham, G . ; R o b e r t s o n , V . A . W . ; and R a t t r a y , E . A . S . 1972. F u r t h e r O b s e r v a t i o n s on Stomach F u n c t i o n o f S c o u r i n g Piglets. Proc. Nutr. Soc. 31:67-71. W h i t e , F . ; Wenham, G . ; Sharman, G . A . M . ; J o n e s , A . S . ; R a t t r a y , E . A . S . ; and McDonald, I. 1969. Stomach F u n c t i o n i n R e l a t i o n t o a Scour Syndrome i n the P i g l e t . B r . J . Nutr. 23:847-858. Widdowson, E . M . 1971. I n t r a - u t e r i n e Growth R e t a r d a t i o n i n the P i g . I. Organ S i z e and C e l l u l a r Development a t B i r t h and A f t e r Growth to M a t u r i t y . B i o l , o f the Neonate 19:329-351 W i l s o n , M.R. 1974. Immunologic Development o f the Neonatal P i g . J . An. S c . 38:1018-1021.  

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