Cellular and humoral bronchopulmonary immune response of rabbits immunized with thermophilic actinomyces antigen.
The immunologic events involved in the pathogenesis of human hypersensitivity pneumonitis are poorly understood. To delineate better the cellular and humoral bronchopulmonary response to host challenge with an important agent for hypersensitivity pneumonitis, an animal model was developed. Rabbits intratracheally inoculated with Micropolyspora faeni antigen developed histologic lesions resembling hypersensitivity pneumonitis in man, characterized by a mononuclear cell interstitial reaction and a marked increase in the number of intra-alveolar cells. This reaction was intense 8 days after immunization and progressively decreased in intensity, with complete resolution occurring, in some instances, by 3 weeks. The increased intra-alveolar cells were predominantly macrophages, but soon after immunization, greater numbers of lymphocytes and granulocytes were present. Associated with the intra-alveolar macrophage response was the appearance of "activated" macrophages, based on increased glucose oxidation and ultrastructural appearance. The immunized rabbits demonstrated Arthus-type skin reactions, as well as delayed hypersensitivity skin reactions after intradermal injection of M. faeni antigen. Alveolar macrophage migration was significantly inhibited in immunized rabbits in the presence of M. faeni antigen, suggesting that specifically sensitized lymphocytes were present in the free bronchoalveolar cell population. Intratracheal inoculation with M. faeni resulted in the production of anti-M. faeni-precipitating antibodies in the sera of all animals and in bronchoalveolar secretions in 15 of 16 inoculated rabbits. The concentrations of IgG and IgA in lung-wash fluid were significantly greater in immunized animals. In the immunized rabbits, the mononuclear cell response, positive M. faeni-induced direct migration inhibition factor assays, and delayed skin reactivity strongly suggested the presence of a delayed hypersensitivity component in disease pathogenesis. The presence of precipitating antibody and the increased concentrations of immunoglobulins were consistent with stimulation of the humoral immune system; however, the role of humoral mechanisms in the pathogenesis of the pulmonary lesions is less certain than that of delayed hypersensitivity.
D000818:Animals; D001772:Blood Cell Count; D002464:Cell Migration Inhibition; D004195:Disease Models, Animal; D005260:Female; D006968:Hypersensitivity, Delayed; D007109:Immunity; D007111:Immunity, Cellular; D007070:Immunoglobulin A / Q000032:analysis; D007074:Immunoglobulin G / Q000032:analysis; D007075:Immunoglobulin M / Q000032:analysis; D008168:Lung / Q000276:immunology* / Q000473:pathology; D008848:Micromonosporaceae / Q000276:immunology*; D011233:Precipitin Tests; D011650:Pulmonary Alveoli; D011817:Rabbits; D012130:Respiratory Hypersensitivity / Q000175:diagnosis / Q000276:immunology* / Q000473:pathology; D012882:Skin Tests
D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007075:Immunoglobulin M