The long-term objectives of this proposal relate to several immunological aspects of murine infections with Schistosoma mansoni. Areas that concern resistance/vaccine development are to be studied by examination of humoral and cell-mediated responses against immunogenic membrane vesicles prepared from schistosomules. The use of these liposome-like vesicles in immunization studies will be assayed by cercarial challenge and immune response evaluations. Immunosuppressive effects attributed to the """"""""coat"""""""" material sloughed upon cercarial-to-schistosomular transformation will be investigated. Studies of immunoregulatory events during schistosomiasis mansoni are to involve analysis of the source and nature of soluble suppressor factors from lymphoid tissues of chronically infected mice, and an evaluation of soluble egg antigen induced tolerance. Several of these areas will draw upon the production and use of antigen-specific T cell lines and clones. These data should add to an understanding of immunoregulatory phenomena in schistosomiasis and various other disease states characterized by chronic antigenic exposure. Further studies into the basic immunological interactions that occur in such chronic conditions will be sought through in-depth evaluations of thymic participation in antigen handling. Phenotyping of thymic lymphoid and stromal cells during infection will be coupled with studies to determine if schistosomal antigens occur in the thymus and, if so, whether they are immunogenic, toleragenic, or inert. Interactions between eosinophils and cell-mediated immune responses will be studied to help better define the role(s) of the eosinophil in this infection. The studies proposed are intended to investigate the host-parasite relationship in this chronic infection and provide data that may be applicable to a variety of unrelated but similar clinical conditions.
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