CELLULAR BIOLOGY AND IMMUNOLOGY OF LEISHMANIASIS

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We propose to study host-parasite interactions in Leishmaniasis, with the long range goal of identifying parasite antigens which could be used in a vaccine. The importance of these studies derives not only from the public health significance of leishmaniasis to certain developing countries, but also as an excellent model for understanding the immunology and cell-biology of intracellular infections generally. We will test our hypothesis (based upon compelling preliminary observations) that Leishmania attach to mononuclear phagocytes via fibronectin (FN) absorbed on their surface. We will attempt to identify FN on the parasites by 1) surface iodination followed by immunoprecipitation with anti-FN antibody and SDS-PAGE; 2) immunofluorescence with specific anti-FN antibody; and 3) immune electron microscopy. We will seek evidence for a FN receptor by measuring 125I-FN binding to parasites and binding of parasites to FN-coated surfaces. We will prevent binding of parasites to monocytes and other cells with anti-FN antibody, exogenous FN, and by removal of FN receptors. Studies will be initiated to isolate a FN receptor from promastigotes. Cell-mediated immunity will be studied by examining the ability of draining lymph node lymphocytes to induce leishmanistatic/'cidal mechanisms in L. tropica infected macrophages in vitro. Variables to be assessed include antigen specificity, genetic restriction, and identification of effector cell phenotype. We will develop monoclonal antibodies to identify antigens recognized in this reaction by blocking effector cell function in vitro. Subsequent isolation and purification of these antigens could be used in a vaccine.