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Mechanisms of modulation of immune responses during blood-stage malaria

Authors
Publisher
McGill University
Publication Date
Keywords
  • Malaria -- Immunological Aspects.
Disciplines
  • Biology

Abstract

In this thesis, mechanisms of immunoregulation by CD4$ sp+$ T cells during blood-stage P. chabaudi AS infection in C57BL/6 mice were studied. The kinetics of in vitro production of the Th1-derived cytokine, IFN-$ gamma$, versus the Th2-derived cyokines, IL-4, IL-5 and IL-10, by spleen cells as well as of polyclonal and malaria-specific antibodies in the sera were examined during infection using enzyme-linked immunosorbent assays. Upon antigenic stimulation, spleen cells were found to produce high levels of IFN-$ gamma$ several days prior to peak parasitemia, while high levels of IL-10 production occurred at the time of peak parasitemia followed by IL-4 and IL-5 later in infection. The levels of polyclonal IgG2a isotype were found to be increased during both the acute and chronic phases of infection, whereas the levels of polyclonal IgM, IgG1 and IgG2b isotypes were found to be increased only during the chronic phase of infection. High titers of malaria-specific IgG2a and IgG1 were detected during the primary as well as secondary infections. Investigation of in vitro proliferation of spleen cells to mitogens and malaria specific antigen revealed that the responses of splenic lymphocytes from infected mice to Con A, PHA and LPS were suppressed, with the most severe suppression occurring during the first 14 days post infection. Evidence is provided demonstrating that nitric oxide (NO) and prostaglandins (PG), products of activated macrophages, mediated suppression of lymphocyte proliferation in response to Con A and PHA, whereas only PG were found to suppress LPS-stimulated proliferation. In addition, NO was found to mediate suppression of proliferation of spleen cells from infected mice in response to parasite antigen. Taken together, results from these studies suggest that immune activation and immunosuppression occur simultaneously during blood-stage malaria with P. chabaudi AS infection in C57BL/6 mice. (Abstract shortened by UMI.)

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