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Dissertation/Thesis Abstract

Follicular Helper T Cell Differentiation During Plasmodium Infection
by Wikenheiser, Daniel James, Ph.D., University of Arkansas for Medical Sciences, 2016, 240; 10247660
Abstract (Summary)

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.

Indexing (document details)
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
Subjects: Immunology
Keywords: Antibody, Germinal center, Malaria, Plasma cell, Plasmodium, Tfh
Publication Number: 10247660
ISBN: 978-0-355-06499-5
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