BASOPHIL HYPERSENSITIVITY AND IMMUNE HOST RESISTANCE

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The purpose of these studies is to determine the role of elements of immediate hypersensitivity - allergic disease mechanisms, such as basophils, mast cells and anaphylactic antibodies (IgE and IgG1 in animals), in immune resistance responses to parasites. Ticks are important ectoparasites of animals and humans and are also vectors of many infectious agents. Immune resistance responses to ticks are accompanied by very large basophil infiltrates. We have found that basophils are required to effect this immune rejection of ectoparasites and that the infiltration of basophils is dependent on anti-tick IgG1 antibodies and on sensitized cells. In planned new experiments we will determine whether host Fc receptors are involved in the mechanism of action of these antibodies that mediate immune cutaneous basophil resistance responses to ticks. We will also determine if IgE antibodies are similarly involved and we will identify whether T cells are responsible for cell-mediated resistance. These latter studies will be accomplished by fractionation of sensitized cells in vitro and also by treatment in vivo with monoclonal anti-T cell antibodies. The mechanism of basophil dependent resistance to ticks will be investigated in experiments dealing with basophil derived mediators such as histamine, procoagulants and products of arachadonic acid metabolism. In subsequent experiments we will investigate whether newly recognized antigen specific T cell factors are involved in basophil-dependent immune resistance responses to ectoparasites (ticks) in guinea pigs. These studies should further advance knowledge of immune resistance to parasites, and should also provide more information about the biological value of allergic disease mechanisms.