Infection with Candida albicans is a serious cause of morbidity in the immunocompromised individual. Patients with Acquired Immune Deficiency Syndrome (AIDS) frequently develop severe candidal esophagitis. Patients receiving chemotherapy are also at increased risk for invasive candidiasis. In both cases, the morbidity directly associated with the organism itself is compounded by the increased risk for bacterial superinfection, the significantly compromised nutritional status of the patient, and problems associated with an inability to parenterally administer medication. The initiation of invasive candidiasis is associated with a defective Cell Mediated Immune system while the propagation of the disease may be associated with active immunosuppression mediated by the organism itself. This proposal is directed primarily toward an investigation of the latter element of this disease process. Studies carried out in our laboratories have demonstrated that components of the Candida cell wall possess significant immunomodulatory activity. Accessory cells, B-lymphocytes, and T-lymphocytes all participate in this immunomodulatory process. Immunological and biochemical approaches will be taken to isolate molecules from the cell wall of C. A albicans. These components will then be further purified using one or both of the following biological activities to detect active fractions. The fractionated components will be analyzed for their capacity to manifest immunosuppressive activity. The fractionated and nonfractionated components will also be studied to detect accessory cell modulatory activity, and the participation of the accessory cells in the immunosuppressive function of these components. These studies, using experimental approaches which are currently in use in our laboratories, should contribute new information to our understanding of the ability of the organism to directly induce the immunoregulatory apparatus of the immune system.
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