The long term objective is to determine the immunologic mechanisms in the pathogenesis of infection by the lymphatic-dwelling filariae. These infections, medically important in many tropical and subtropical areas, produce a range of clinical manifestations considered to be immunologically mediated but the immunologic mechanisms are not completely known. More detailed knowledge of the immunopathology would be of potential value for designing treatment regimes and development of immunization procedures. The proposed study will investigate the immunopathology of two manifestations of infection: tropical filarial eosinophilia (occult filariasis) and chronic lymphedema. The ferret (Mustela putorius furo) infected with Brugia malayi will be used as an experimental model.
Four specific aims are proposed. (1) To characterize the cellular responses to microfilariae in the liver resulting in the lesions of tropical eosinophilia and to identify the immune responses associated with development of these lesions. (2) By passive transfer of sera and measurement of antibody activity in the sera, to identify antibody responses which promote or inhibit the inflammatory reactions typical of tropical eosinophilia and to correlate these observations with in vitro studies of opsonic, cytophilic and blocking activity of the sera in leukocyte adherence and cytotoxicity tests with microfilariae. (3) To identify cytokines regulating eosinophil activity in infected ferrets by assays for chemotaxis/chemokinesis and by activation of adherence and cytotoxicity to microfilariae. (4) To examine the immune responses and the lymphatic pathology associated with the development of chronic edema in ferrets repeatedly infected with Brugia malayi.
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