STUDIES OF THE IMMUNOLOGIC RESPONSES TO FILARIAL INFECTIONS

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The purpose of this project is to define the humoral and cellular immune responses that relate to immunopathology, protective immunity and immunodiagnosis of patients with lymphatic filariasis and onchocerciasis. Considerable effort has been directed towards developing monoclonal antibody reagents (Mcabs) for improving the sensitivity/specificity of several of the laboratory's important assays. Thus, antibodies of the IgG subclasses (which appear differentially important in blocking immediate hypersensitivity reactions (IgG4) and in the pathogenesis of lymphatic lesions (IgG3) can be measured by well characterized and highly specific Mcabs; eosinophils can be identified by Mcabs directed against a unique surface antigen; their granule contents (MBP, EOP, EDN and ECP) are now assenssable with affinity purified polyclonal and monoclonal antibodies; and the 200 kD circulating filarial antigen seen in infected patients can be measured much more sensitively with Mcabs directed against it or its immunodominant phosphorylcholine determinant. Studies of eye tissue and fluid from patients which ocular onchocerciasis show active local IgG and IgE antibody production as well as endothelial cell activation (Ia+) in the presence of microfilariae in the eye. T-cell infiltration of the iris and conjunctiva, however, is of the suppressor/cytotoxic phenotype (Leu 2a), opposite to the findings in most uveitis syndromes but consistent with the general parasite-specific, primary T-cell immunosuppresstion repeatedly demonstrated in both onchocerciasis and lymphatic filariasis.