With PQDT Open, you can read the full text of open access dissertations and theses free of charge.
About PQDT Open
Search
COMING SOON! PQDT Open is getting a new home!
ProQuest Open Access Dissertations & Theses will remain freely available as part of a new and enhanced search experience at www.proquest.com.
Questions? Please refer to this FAQ.
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 |
Source Type: | DISSERTATION |
Subjects: | Immunology |
Keywords: | Antibody, Germinal center, Malaria, Plasma cell, Plasmodium, Tfh |
Publication Number: | 10247660 |
ISBN: | 978-0-355-06499-5 |