title: Louis E. Siltzbach Memorial Lecture. Concepts of pathogenesis and lung reactivity in hypersensitivity pneumonitis.
abstract: It is surprising that forms of hypersensitivity pneumonitis do not occur more frequently, given the variety of biologic dusts and airborne antigens that have been found to cause disease. Exposure is almost universal in some occupations that involve handling animals or feed products, and development of humoral immunity occurs in most; however, overt respiratory illness is relatively infrequent or not easily recognized by the subject. What differs between symptomatic and asymptomatic subjects is not certain, but unique host resistance or susceptibility, as the case may be, appears to be a factor. This may have a genetic basis, but this has not been investigated vigorously. With repeated airborne exposure to appropriate antigens, a humoral and a local respiratory antibody response occur but perhaps with little disease consequence, as most subjects so immunized remain clinically asymptomatic. So far as is known, there is no other route of antigenic exposure except through the respiratory tract, but contact with the antigens could occur on the skin or on mucosal surfaces such as the conjunctiva, or antigens could be ingested by swallowing nasopharyngeal secretions. Except for serum antibodies, however, there is little documentation that other systemic organs are affected, as may occur with sarcoidosis. Of course there is great variability in the age of the subjects and the dosage of antigen to which the subject is exposed, and the frequency and duration of exposure can vary considerably. All of these would seem to be easily tested, however, in an animal model where most of the variables could be independently controlled and varied at will. Even the genetic and aging factors, which are the most difficult parameters to control in humans, could be investigated. Yet, it has been very difficult and perplexing not to have created a more faithful model of hypersensitivity pneumonitis in the laboratory. It is virtually impossible to cause predictable lung disease without the use of an adjuvant that will induce some measure of delayed or cellular hyperreactivity. The acute lung disease caused by antigen-antibody reactions seems too explosive and severe, for its acute disease counterpart of hypersensitivity pneumonitis in humans and the persistence of histologic changes in lung tissue is brief and is usually resolved within 1-2 weeks. A chronic model producing granulomas and fibrosis has been difficult to construct, although the work reported by Fulmer and colleagues is very encouraging.(ABSTRACT TRUNCATED AT 400 WORDS)
mesh_terms: D000208:Acute Disease; D000542:Alveolitis, Extrinsic Allergic / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D000818:Animals; D001716:Bird Fancier's Lung / Q000209:etiology / Q000276:immunology / Q000473:pathology; D002908:Chronic Disease; D004195:Disease Models, Animal; D004391:Dust / Q000009:adverse effects; D005203:Farmer's Lung / Q000209:etiology / Q000276:immunology / Q000473:pathology; D006168:Guinea Pigs; D006801:Humans; D007114:Immunization / Q000379:methods; D008168:Lung / Q000276:immunology* / Q000473:pathology; D008253:Macaca mulatta; D011650:Pulmonary Alveoli / Q000276:immunology / Q000473:pathology; D011817:Rabbits; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D004391:Dust