In Nippostrongylus brasiliensis rats, tracheal sensitivity to worm allergens developed prior to intestinal sensitivity and correlated with the early local synthesis of reaginic antibody in the mediastinal (bronchial) lymph nodes. Skin and intestinal sensitivity to worm allergens more nearly correlated with serum reaginic antibody and its synthesis by mesenteric lymph nodes and other tissues. Prostaglandins appeared to modulate intestinal responsiveness to worm allergens. Thus, local reagin synthesis and other microenvironmental factors influence local tissue sensitization and responsiveness to allergens.

Guinea pigs subjected to intranasal dusting with ragweed (RW) pollen or intranasal instillation of RW extract (RWE) showed anaphylactic reactions when subjected to RW extract aerosol (RWEA). These animals, however, did not respond to an aerosol of RW whole pollen. Animals which received the RWEA treatment prior to nasal dusting with RW pollen showed no subsequent anaphylactic reactions when exposed to RWEA. Both the aerosol-sensitive and the aerosol-nonresponsive animals exhibited high titers of homocytotropic antibodies to RWE. In addition, the aerosol-nonresponsive animals also had precipitating antibodies of IgG type. The state of nonresponsiveness did not appear to be due to the precipitating antibodies, since this condition could not be passively transferred by sera and blocking antibody activity was not demonstrable.

Nonresponsiveness to aerosolized antigen induced by repeated exposure of guinea pigs to either bovine serum albumin (BSA) or ragweed (RW) aerosols was not antigen specific, since induction of lung sensitization with the same, as well as heterologous antigen, was prevented. However, prior lung sensitization to an antigen was maintained in spite of subsequent treatment with aerosolized antigen. In this case treatment with aerosolized antigen could abrogate sensitization of the lung to all subsequent antigens. Chopped lung pieces could not be passively sensitized by antisera to homologous or heterologous antigens unless they were previously treated at low pH. High levels of conventional and homocytotropic antibody were demonstrated in nonresponder animals. Nonresponsiveness induced by fed antigen, however, was antigen specific, and elevated homocytotropic antibody levels were not present. Aerosol-induced nonresponsiveness appears to be a local phenomenon which involves a blocking of the pulmonary mast cells by immune complexes or other blocking factors so that they can no longer respond to antigen challenge.