UBC Theses and Dissertations

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UBC Theses and Dissertations

Ontogeny and genetic correlates of the TLR mediated pediatric innate immune response Corbett, Nathan Patrick


In early life, humans are particularly vulnerable to morbidity and mortality due to infectious disease. A key system that is critical to both early response to pathogens, and also to the success or failure of a vaccine to induce protective immunity is the innate immune system. It is our working hypothesis that changes in the developing immune system mediate changes in both vaccine response and infectious morbidity and mortality. This thesis presents published and unpublished work wherein we analyze the innate immune response of a defined population of newborns from the greater Vancouver area in British Columbia, Canada. In this work, we set out to define the development of early response by the human infant immune system to molecular danger signals known as pathogen-associated molecular patterns (PAMPS) by the well-defined Toll-Like Receptor (TLR) system expressed by peripheral blood mononuclear cells (PBMC). In addition, we have correlated this response with the occurrence of pertinent genetic variance between individuals, in the hope of identifying immune modulating variants in situ. Such variants will provide the basis for later testing of our hypothesis that genetic variance in early life innate immune response contributes to the significant variability in morbidity and mortality.

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