IMMUNOREACTIVE MACROMOLECULES IN COCCIDIOIDES CELL TYPES

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Coccidioides immitis is a pathogenic fungus which is the causative agent of a primary respiratory infection of man and other animals. It is endemic to southwestern United States from California to Texas and its natural habitat is arid soil. The saprobic phase of this fungus releases infectious propagules, or, arthroconidia, into the air which are inhaled by the host. About 100,000 people are infected each year. Although less than half of these infections produce symptoms, those that do account for a significant amount of morbidity and mortality. The latter is limited to individuals who suffer extrapulmonary spread of the infection. This organism is unique among fungi in that the parasitic stage occurs in a repetitive morphogenetic cycle involving conversion of the propagule into a multinucleate spherule which subsequently cleaves internally to produce a myriad of tiny endospores. The latter disseminate within the host and convert into a new generation of spherules. These morphological forms are associated with different tissue responses; e.g., the spherules are associated primarily with granulomatous response and the relased endospores with suppurative response. Thus, C. immitis is an ideal model for examining the intricate mechanisms by which the host cells respond to the insult of the propagule and successive cell types of the parasitic cycle. Such host-pathogen interactions are poorly understood in this and other mycotic diseases. Evidence has been presented that antigenic composition of the cell envelope of C. immitis is altered during morphogenesis. Such changes may be related to variations in host response. Published data also indicate that clinically significant biological activities associated with this disease, including cell-mediated immune responses, reactivity with immununoglobulin antibody and immunoprotection against challenge in experimental animals are elicited by cell wall fractions. The aims of this project are to identify the antigenic composition and biological activity of fractionated soluble wall components of C. immitis cell types, prepare polycolonal and monoclonal antibodies to these fractions and assess the homogeneity of the fractions, determine the location and/or presentation of antigens on the cell envelope using cell surface probes, and evaluate the immunoprotective capacity of the fractions in experimental animals. The results of these studies will provide for improved immunodiagnosis of the various clinical manifestations of coccidioidomycosis as well as the basis for developing a human vaccine against this fungal disease.