STUDIES OF THE IMMUNOLOGIC RESPONSES TO FILARIAL HELMINTH 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. Antibodies of the IgG subclasses appear differentially associated with the clinical manifestations of bancroftian filariasis; patients with elephantiasis have prominent IgG3 antifilarial antibodies and minimal IgG4 responses while the opposite is true for those with asymptomatic infection. Studies of eye tissue and fluid from patients with ocular onchocerciasis show active local IgG antibody production but little or no indication of a pathogenetic role for IgE in these lesions. T-cell infiltration of the iris 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 immunosuppression demonstrated in both onchocerciasis and lymphatic filariasis. The eosinophil granule protein MBP, important in the pathology of helminth infections, can now be defined in tissues by immunofluorescence and in fluids by immunoassay with monoclonal antibodies. Populations with onchocerciasis or bancroftian filariasis have been examined to define immunologic parameters that distinguish 'naturally' immune form infected individuals. A 43Kd protein from infective larvae appears as a potential protective immunogen for bancroftian filariasis, and specific probes are being generated to study it further.