Hypersensitivity pneumonitis--pathology and pathogenesis

Abstract

Early reports of hypersensitivity pneumonitis postulated that the disease was infectious or resulted from the toxic properties of the inhaled organic dusts. The finding of precipitating antibodies to moldy hay in farmers afflicted with farmer's lung suggested a role for antibody in pathogenesis, and a type III (antigen-antibody complex-mediated or Arthus) hypersensitivity reaction based on the classification of allergic reactions by Gell and Coombs was postulated. Subsequent studies have indicated the importance of cell-mediated (delayed) hypersensitivity (type IV). It must be recognized that hypersensitivity mechanisms are quite complicated and that the classification of Gell and Coombs is an oversimplification; interreacting humoral and cellular responses are typical of most hypersensitivity reactions of whatever classic type as originally defined. The prime importance of T-cell- and macrophage-mediated inflammation in HP, however, is indicated by histopathology, animal models, and in vitro correlates in humans. Major difficulties in defining completely the exact effector mechanisms involved in the pathogenesis of HP include the absence of a reliable in vitro correlate of antigen-specific effector T cells (the so called TDH cell) and the overwhelming versatility of the macrophage. There is no direct evidence to support contributions by precipitins, complement, or genetic host factors in the pathogenesis of hypersensitivity pneumonitis, nor are there studies as yet of cellular cytotoxicity contributions. Cellular and antibody interactions may lead to immunosuppressive processes modulating inflammatory responses and preventing disease despite immunogenesis. Animal models are helpful in dissecting mechanisms and defining effector functions. The eventual goal in studies of pathogenesis is to provide better tools for definitive diagnosis and methods of disease prevention, modulation, and cure.