Candida albicans is a major pathogen in the immunocompromised individual. Since acquired immune mechanisms in the normal individual are poorly understood, management of the immunocompromised individual is often empirical. Further, individuals with serious candidal disease often have circulating antigen; its effect on the immune system is poorly understood. The major objectives of this research, therefore, are to define the lymphocyte classes involved 1) in acquired immunity to C. albicans, and 2) in immunomodulation induced by circulating Candida antigen. All experiments will be done in a murine model of experimental candidiasis. Two approaches will be taken to investigate the first objective, 1) transfer of lymphoid cells from immunized donors to naive recipients, and 2) anti-mu suppression of mice. Populations of T, B or T-subset lymphocytes, isolated by panning or prepared by cytotoxic antibody depletion, will be obtained from animals immunized by cutaneous inoculation of viable C. albicans. Following transfer, recipients will be challenged intravenously with viable C. albicans and organs will be cultured after a suitable interval to assess protection. To assess the role of antibody in a protective response, animals will be suppressed by inoculation of anti-mu from birth, then as adults, they will be immunized and immune responses measured, including resistance to systemic challenge. Transfers of Candida-specific antibody into anti-mu treated mice may be done also. Since mannan extracted from C. albicans can be separated by ion- exchange chromatography into components which have either enhancing or suppressing effects on antibody responses to type III pneumococcal polysaccharide (SSS-III), a T helper cell- independent antigen, and sheep erythrocytes (SRBC), a T helper cell-dependent antigen, the cellular targets for the regulatory phenomena will be studied. Splenic antibody-forming cells will be quantitated by plaque assay, following transfers of lymphoid populations from immunized and mannan-treated donors into naive recipients. Studies to determine possible immunoregulation by mannan on delayed hypersensitivity (DTH) will involve giving mannan to mice at various times with respect to immunization with SRBC followed by assessment of DTH in vivo by footpad testing. If time permits, investigations of interleukins and gamma interferon as potential mediators of the regulatory phenomena observed will be begun.
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