There is a substantial, growing body of knowledge on the role of host immunity in infectious disease, the immunological factors responsible for retardation of expression of disease and methods of modifying host susceptibility. This information is often derived from clinical observations of patients with either congenital or acquired states of dysimmunity and has become particularly important for a number of chronic pulmonary infections. We have selected three such pathogens (Nocardia asteroides, Mycobacterium intracellulare, and Candida albicans) because of their importance as primary and secondary opportunistic infections as well as the critical interrelationships between T cells, B cells and macrophages in host-lung responsiveness to these organisms. To study the role(s) of host immunity towards these agents we plan to make use of and manipulate immunologically a number of versatile murine mutants, including congenitally athymic (nude) and hereditarily asplenic (Dh/+) mice. Groups of these mice will be infected with selected strains of N. asteroides, M. intracellulare and C. albicans using subcutaneous (footpad), intravenous, intranasal, and aerogenic routes. The dose response characteristics, latency periods, host clearance rates, histologic parameters, ultrastructural characteristics and host-immune processes will be studied. The lung responses and host-parasite interactions will be determined. These models should allow us to determine the role(s) of T cell and B cell populations in host-lung defense; how T cells interact with B cells and macrophages in response to these agents; and how these organisms may alter specific host responsiveness that may permit them to overcome "normal" host defenses in the uncompromised host.