Three subjects are proposed for study: a) Immunoregulation of Schistosoma mansoni and S. japonicum granulomas in mice and of S. haematobium granulomas in baboons; b) Effector sequence and cellular mechanisms of immune parasite killing in mice vaccinated with live, X-ray-attentuated vaccines against S. mansoni. c) Immunopathology of early, experimental cutaneous leishmaniasis in a murine ear model, comparing defined geographic Leishmania strains. Histopathologic and immunocytochemical methods in vivo will be used throughout, and the following objectives will be emphasized: a) Differences between S. mansoni and S. japonicum granulomas as respects their immunoregulation; cellular-versus humoral modulatory mechanisms; effects of live vaccines on the subsequent pathology of patent schistosome infection. b) The exact timing and sites of attrition of schistosomula in the vaccinated mouse, and the cellular requirements for immune parasite killing in vivo. c) Histopathological differences between early leishmanial skin lesions due to regional parasite strains, and analysis of the immunoregulatory host cells in these lesions, as defined by immunospecific cell markers. All three studies seek a better understanding of the protective and immunoregulatory cellular host responses to parasitic infections and should help in designing better immunotherapeutic measures applicable to animals or humans.
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