The generation of specific IgE and IgG against inhaled indoor allergens has been well established in both experimental animals and humans with allergic disease. Obviously, biological inhalant proteins carried into the airways on particles that range in size from 0.1 to 50 μm in diameter are most likely to generate an immune and allergic response in both the upper and lower airways. Little is known about the exact kinetics and concentration of inhaled allergen necessary to generate a response of this sort either in animals or in human subjects. It is enough to say that the airways and lungs can be an important portal of sensitization to foreign proteins and in particular to certain allergens found indoors. The kinetics of antibody formation and recognition are not well established because standardized methods of identifying allergen exposure on inhalation in the natural environment or under experimental conditions have not been developed. Nonetheless, one may be sure that the cells of the airways are interacting in such a way as to generate the appropriate phenotype of an allergic response in subjects who inhale protein allergens. Table 4-5 lists potential immunologic hypersensitivity reaction mechanisms in the allergic diseases associated with inhaled allergen exposure.
The potential role of T cells and cytokines in the regulation of IgE-mediated and hypersensitivity pneumonitis responses to inhaled proteins is of great interest. Ongoing research has found that inhaled protein allergens are processed by bronchial macrophages and other antigen-presenting cells in such a manner that allergenic peptides are then recognized by CD4+ T helper cells in the airway. These allergen epitope-specific T cells in the airways of atopic asthmatic individuals are critically involved in the generation of proinflammatory mediators; these mediators, which include the whole panoply of cells outlined in the previous section, subsequently recruit the various kinds of factors and cells related to and associated with airway inflammation and hyperreactivity. In particular, the CD4+ TH2 subset of T lymphocytes, when activated by allergen presented in the context of class II MHC molecules on an antigen-presenting cell, stimulates the generation of cytokines such as IL-3, IL-4, IL-5, and GM CSF. Cytokine production leads to the activation and recruitment of other allergy accessory cells in the airway (e.g., mast cells, eosinophils, basophils, and neutrophils). In fact, recent data suggest that the TH2 population of cells in humans is preferentially activated in response to the unique structures associated with allergens, and it has been shown that these kinds of cells produce these cytokines in response to allergen in the airways. An allergic proinflammatory process thus can be set up on the basis of recognition of an inhaled protein allergen. Other trigger factors may also play a role in this inflammatory milieu. An example is the potential action of a viral infection. When activated in a