The proposed research is designed to investigate the relative roles of the cell-mediated and humoral arms of the immune system in experimental candidiasis. Attempts will be made to demonstrate either protection or increased susceptibility in animals, primarily CBA/J mice, when they are immunosuppressed or immunostimulated. Immunosuppression of the cell-mediated system will be accomplished by adult thymectomy, and of the humoral system by carefully balanced administration of cyclophosphamide. Further immunologic modification of animals will be attempted by the intravenous inoculation of subcellular fractions of C. albicans in such a manner as to induce tolerance. Animals will be immunostimulated by immunization with subcellular fractions of C. albicans emulsified in Freund's complete adjuvant, the subcellular fractions having been derived from a series of differential centrifugations following mechanical breakage of Candida, and also from chemical extraction of cell wall preparations. Assessment of protection or increased susceptibility will be by cutaneous and intravenous challenge. In all the types of animals, any cell-mediated and humoral responses induced by artificial immunization or by infection will be determined at selected times during the course of the experiments. Cell-mediated responses will be determined in vivo by footpad testing and cell tranfer studies, and in vitro by assay of macrophage migration inhibition factor. Humoral responses will be determined by standard techniques such as immunodiffusion, complement fixation, and immunofluorescence. Attempts will be made to relate these findings to mechanisms of host resistance to Candida.