Trachoma is one of the most prevalent infectious diseases of mankind and the leading cause of blindness. However, many features of trachoma are still unexplained. On the one hand, there is appreciable evidence that local (and perhaps systemic) immune responses to chlamydial antigens are responsible for much of the pathology observed in this disease. However, there is also suggestive evidence that local and/or systemic immune responses may simultaneously afford a measure of protection against chlamydial infection. It is, therefore, the main purpose of these investigations to clarify this apparent and almost paradoxical dichotomy. The specific objectives are: 1. To characterize the various components of the local immune response in the conjunctiva to chlamydial infection. 2. to characterize the local and systemic immune mechanisms, both humoral and cell-mediated, which contribute to the resistance to chlamydial infection. 3. To investigate methods for the selective immunization to various chlamydial antigens paying particular attention to stimulation of the secretory immune system by employing enteric vaccines. The studies will be conducted in an experimental animal model of trachoma that has been developed in cynomolgus monkeys which receive repeated infections with Chlamydia trachomatis. The study will take advantage of recent advances in immunological and experimental pathologic techniques to clarify the pathogenesis of this disease. These techniques will include specific monoclonal antibodies to T-cell surface antigens and to immunoglobulin isotypes; immunoperoxidase and immunofluorescent staining methods; and the use of purified chlamydial antigens. The efficacy of various routes of immunization and the effect of different immunosuppressant agents will be studied to gain further information on the pathogenesis and to provide information on protective immunity. It is anticipated that these studies will have considerable importance not only in the fields of opthalmology and immunology but also in the wider areas of infectious disease and preventive medicine.
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