Experimental production of granulomatous pneumonitis. Comparison of immunological and morphological sequelae with particulate and soluble antigens administered via the respiratory route.

Rabbits were sensitized with either a soluble protein antigen (BSA) or a particulate thermophilic actinomycete antigen (Micropolyspora faeni) via the respiratory route, followed by monitoring of sequential morphologic changes and the humoral plus cellular immunologic response. Primary respiratory tract sensitization with BSA resulted in a humoral anti-BSA response, Arthus and delayed skin reactivity, and in some cases specific antigen-induced alveolar macrophage migration inhibition, all in the absence of pulmonary lesions. Lesions characterized by mild multifocal perivascular mononuclear cell infiltrates in the lungs developed only after secondary BSA aerosol challenge. In contrast to these findings, "primary" respiratory tract sensitization with M. faeni particulate antigen in saline solution resulted in the gradual development of extensive and progressive pulmonary interstitial and alveolar mononuclear cell infiltrates. These lesions were uniformly associated with specific serum precipitating antibody and delayed skin reactivity. Alveolar macrophage migration was significantly inhibited by Micropolyspora faeni in virtually of these animals. These results, while not excluding a primary irritant effect or Type II or III alergic tissue injury, suggest a role for delayed (cell-mediated) hypersensitivity in the pathogenesis of particulate actinomycete-induced pulmonary lesions. They also indicate that primary immunization with soluble purified protein antigens via the respiratory route can lead to systemic humoral and cell-mediated immunity without production of pulmonary lesions.