This proposal will investigate several interrelated immunologic aspects of the basic host-parasite relationship in the mouse model of schistosomiasis mansoni. This important, wide-spread worm infection is prevalent in much of Africa, the Caribbean and South America. The long term objective of this research is to understand sufficiently the balance between host and parasite to allow manipulation of the system in favor of the host. These studies should improve the understanding of cytokine/lymphokine involvement in the production and immunoregulation of the primary pathogenic mechanism in murine schistosomiasis the schistosome egg-induced granuloma (Specific Aim #1).
Specific Aim #2 seeks to define major cross-reactive, immunoregulatory idiotypes which are expressed on antibodies specific for schistosome soluble egg antigens (SEA) and elucidate their role in granuloma modulation at the antibody and T lymphocyte levels. Examination of the potential role (s) of gamma/delta (gammadelta+) T cell receptor- bearing T lymphocytes at different stages and in certain anatomical locations during schistosomiasis (Specific Aim #3) should yield useful information about the function of these newly studied cells, and may clarify previously unstudied aspects of host responsiveness in schistosomiasis in the dermis, spleen, liver and intestine.
Specific Aim #4 states, and will explore the validity of, a new hypothesis regarding differential T cell responses which result in eosinophilopoiesis in schistosomiasis. The answers to questions posed in these specific aims should provide information that will contribute to our fundamental immunologic knowledge as it applies to schistosomiasis. When germane, data and concepts from these studies bay be useful in understanding other medically important conditions, such as chronic infections, autoimmune diseases, cancer and transplantation. These settings parallel schistosomiasis in the sense that in each the body's immune system must """"""""learn"""""""" to deal with chronic antigenic exposure.
