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Document Type

Open Access Dissertation

Degree Name

Doctor of Philosophy (PhD)

Degree Program

Animal Biotechnology & Biomedical Sciences

Year Degree Awarded

2015

Month Degree Awarded

February

First Advisor

SAMUEL J BLACK

Second Advisor

CYNTHIA BALDWIN

Third Advisor

ROBERT WOODLAND

Subject Categories

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

Abstract

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.

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