Through study of cutaneous basophil hypersensitivity (CBH) it is now clear that basophils and mast cells, their contained mediators (such as histamine and serotonin), and their associated anaphylactic antibodies (IgE and IgG1), are involved in delayed-time course reactions. These findings mean that immune components improtant in allergic disease and astha are also potentially important in immune resistance to microbes and parasites and in rejection of tumors and tissue grafts. This research proposal submits a comprehensive program for the continued investigation of the role of antibodies in CBH responses of guinea pigs. We will study the mechanism by which these antibodies mediate CBH by determining whether circulating basophils, and basophils arriving at CBH reactions are sensitized with antibodies that transfer CBH. We will also determine whether these antibodies are a special subclass of IgG1 and whether lymphocytes or macrophages are involved in the ability of antibodies to mediate CBH. Finally, studies will be performed to determine whether these antibodies are also involved in CBH reactions that are transferred by thymic-derived lymphocytes (T cells). Studies will also be continued on the requirement for T cells to activate mast cells to release the vasoactive amine serotonin in murine delayed-type hypersensitivity (DTH). Serotonin transport from mast cells in DTH, and in vitro will be studied. A mast cell-derived serotonin protein that may be important in transport of serotonin will be characterized. Finally, we will determine the mechanism by which T cells may activate mast cells in DTH by determining whether non-specific serotonin releasing lymphokines, or specific IgF-like factors are involved.
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