The protozoan parasite Plasmodium is the causitive agent of malaria, which remains one of the most prominent public health challenges in the world today. The overall goal of this project is to examine the function of plasma cells as antigen presenting cells (APCs) during a primary and secondary immune response against Plasmodium. We hypothesize that isotype-switched plasma cells will be able to present antigen throughout the primary and secondary immune response against Plasmodium and that these cells will serve to regulate the germinal center response in the spleen, particularly following a secondary infection. We have proposed studies (Aims 1) to investigate the ability of plasma cells to express the machinery necessary for antigen presentation following infection with P. yoelii and to determine the capacity of this cell type to activate a CD4[+] T-cell response, with a specific focus on determining how antigen presentation by plasma cells influences the activity of follicular helper T cells, a specialized subset of T cells involved in antibody production. We will also examine the localization of IgG[+] plasma cells and memory B cells in the spleen to determine how their positioning in the spleen influences the kinetics of a secondary response (Aims 2). A role for plasma cells in the presentation of antigen during Plasmodium infection has not been considered previously, and identifying this cell as a functional APC as well as determining how this cell type regulates a secondary antibody-mediated immune response will further our understanding of how long-term immunity is generated against this pathogen, information that will be pertinant for successful vaccine development.
Malaria results in the death of more children worldwide then any other infectious disease. Thus, an emphasis has been placed on understanding how the immune response, both cell- and antibody-mediated, regulates the outcome of this infection in order to determine how protective immunity can be enhanced in a vaccine setting to ultimately provide and maintain immunity against this disease.
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