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Open Access Dissertation
Doctor of Philosophy (PhD)
Animal Biotechnology & Biomedical Sciences
Year Degree Awarded
Month Degree Awarded
SAMUEL J BLACK
Animal Diseases | Animal Sciences | Biology | Immunology and Infectious Disease | Immunology of Infectious Disease | Immunopathology | Laboratory and Basic Science Research | Life Sciences | Other Immunology and Infectious Disease | Parasitic Diseases | Parasitology
Loss of humoral immune competence in T. brucei-infected mice is associated with the apoptotic depletion of splenic transitional, marginal zone and follicular B cells as well as a depletion of CD8+ T cells. This occurs rapidly after infection and impairs responses to vaccine antigens in addition to responses to newly arising VSG antigenic variants, leading to uncontrolled parasite growth and death of the infected mice. Infection-induced B2 B cell and CD8+ T cell loss requires the presence of a novel population of natural killer (NK) cells and is mediated by a perforin-dependent process consistent with perforin- and granzyme-mediated cytotoxicity. The absence of perforin in deficient mice prevents infection-induced loss of splenic B cells, enhances trypanosome-specific antibody responses, reduces infection-associated anemia and prolongs survival after infection thus enhancing trypanosomiasis-resistance.
Additionally, the parasite enzyme phospholipase C (PLC) is required for B2 B cell and Cd8+ T cell depletion. Abrogation of infection induced immunopathology during infection with a PLC deficient parasite (PLC-/- T. brucei) is dependent on the presence of the antigen presenting molecule CD1d, as B2 B cell depletion and CD8+ T cell depletion occur during infection of CD1d-/- mice with PLC-/- T. brucei. Natural killer cells acquire the same novel phenotype during infection with intact or PLC-/- T. brucei, however only during infection with the intact parasites are the NK cells shown to degranulate.
Frenkel, Deborah, "A Novel Population of Natural Killer Cells Plays a Critical Role in the Depletion of Splenic B2 B Cells During Experimental African Trypanosomiasis" (2015). Doctoral Dissertations. 298.
Animal Diseases Commons, Animal Sciences Commons, Biology Commons, Immunology of Infectious Disease Commons, Immunopathology Commons, Laboratory and Basic Science Research Commons, Other Immunology and Infectious Disease Commons, Parasitic Diseases Commons, Parasitology Commons