The local and systemic IgA and IgG antibody responses of rabbits to a soluble inhaled antigen: measurement of responses in a model of acute hypersensitivity pneumonitis.

We evaluated local and systemic humoral responses to inhalational challenges with ovalbumin (OA) by measuring IgA and IgG isotypic antibodies to OA in serum and bronchoalveolar wash fluids (BAW), and by quantitating cells containing IgA, IgG, and anti-OA in lung, lymph nodes, spleen, and gut. Rabbit models of acute hypersensitivity pneumonitis and chronically-challenged "desensitized" animals were studied along with appropriate control animals. Systemic (via a toe pad) immunization or acute aerosol challenge with OA resulted in only trace amounts of IgG anti-OA antibodies in BAW and no apparent anti-OA-containing cells in the lung itself. Acute aerosol challenge of systemically immunized rabbits caused alveolitis, increased IgG anti-OA-containing cells in mediastinal and popliteal lymph nodes, and increased IgG anti-OA in BAW attributable to transudation from serum. Thrice-weekly inhalational challenge with aerosolized OA resulted in waning alveolitis, elevated concentrations of IgA and IgG anti-OA in BAW and serum, and increased concentrations of IgG and IgA anti-OA cells in the lung, but not in other tissues, including the gut. We conclude that these experiments have implicated IgG as well as IgA antibodies in local humoral responses to inhaled antigen, have not substantiated the notion of a common mucosal immune system involving lung and gut, have failed to demonstrate humoral tolerogenesis after inhalation of antigen, and have shown an effect of systemic priming on subsequent pulmonary immune responses in the models examined.