Plasmodium infection exerts an enormous health and economic burden on a considerable number of individuals worldwide. Indeed, recent estimates suggest nearly 200 million people contract malaria annually, resulting in over 400,000 deaths. Development of a highly efficacious vaccine has been championed as the most cost-effective and rational solution to curtail the prevalence of malaria in sub-Saharan Africa. Here, we assess the development of protective adaptive immune responses that result in the production of high- affinity parasite-specific antibodies (Abs)—a critical component of anti-malarial disease immunity. Using the murine Plasmodium chabaudi chabaudi AS infection model, we demonstrate the development of sustained, high-affinity Ab production, as well as germinal center (GC) formation—the site of Ab affinity maturation—is reliant on the co-stimulatory molecule ICOS. Furthermore, we describe the identification of a unique innate-like T cell responsible for promoting early Ab production during Plasmodium yoelii infection. Lastly, we assess the contribution of memory T cells to secondary GC formation, and demonstrate that Tfh cells derived from memory T cells promote Ab production during secondary Plasmodium challenge. Collectively, these studies provide additional insight concerning the processes of short-lived early Ab production, GC-derived long-lived plasma cell generation, as well as secondary GC formation during Plasmodium re-infection.
|Advisor:||Stumhofer, Jason S.|
|Commitee:||Cannon, Marin, Chow, Marie, Ponnappan, Usha, Post, Steven|
|School:||University of Arkansas for Medical Sciences|
|Department:||Microbiology and Immunology|
|School Location:||United States -- Arkansas|
|Source:||DAI-B 78/11(E), Dissertation Abstracts International|
|Keywords:||Antibody, Germinal center, Malaria, Plasma cell, Plasmodium, Tfh|
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