The research proposed in this application is intended to further clarify mechanisms of host resistance to Pneumocystis carinii and to further explore biochemical characteristics of the organism in vitro. Pneumocystis carinii is a protozoan parasite which causes clinical disease only in severely immuno-suppressed patients. In laboratory rats, prolonged therapy with glucocorticoids induces the disease. Such rats serve as a source of organisms for in vitro studies. Studies of host defenses will be focused on the mechanisms whereby host effector cells, in particular activated macrophages, could be lethal to Pneumocystis and the interaction of the organism with alveolar lining fluids. In both of these aspects, perturbations caused by glucocorticoids will be investigated. In addition, studies of structural and enzymatic proteins of pneumocystis will be carried out, using both gel electrophoresis and monoclonal antibodies. The identity of antigenic proteins and the relevance of antibodies to given proteins to protection from disease will be studied. Characterization of the phospholipids content of the organisms and their interaction with alveolar fluid phospholipids will also be undertaken as will initial characterization of the DNA of Pneumocystis carinii.