Classic Sensitization

The B cell IgE mediates various immediate hypersensitivity states, including typical allergy to biological aeroallergens. IgE mediation is involved heavily in the pathogenesis of asthma (Hetzel and Clark, 1983; Turner-Warwick, 1978). Several chemicals, such as TDI, TMA, platinum salts, form protein bound haptens that act as antigens (Weill and Turner-Warwick, 1981; Brooks, 1982; Chan-Yeung, 1990; Newman-Taylor and Tee, 1990). Basically, IgE forms antibodies to certain antigens/allergens that are inhaled, absorbed, and/or ingested. This is the recognition (and sensitization) phenomena. Specific IgE then persists in the sensitized; it is an outcome that can be assayed. There are IgE receptor sites on basophils and mast cells. When an IgE antibody-antigen binding occurs, the IgE can attach to these receptors. This usually leads to degranulation of the cells and subsequent release of histamine, chemotactic factors for platelets and other active cells (e.g., eosinophils, neutrophils), and other active mediators (e.g., PG's/LTB). This starts a chain reaction (or cascade) of immunochemical phenomena which leads to the hypersensitivity response, and can lead to inflammation. (Ibid.) Anti-IgG can lead to basophil activation as well, as can the cells and some of the chemotactic factors (e.g., PAF) directly (Marone, 1989). (The mechanisms are discussed in more detail in the Immunology and Animal Models section.) IgE is genetically linked, as are other immunoglobulins (Turner-Warwick, 1978; Gregg, 1983; Lebowitz et al., 1984; McGue et al., 1989). IgE also has an amplification-control cycle that probably involves some subsets of IgG and secretory IgA. IgG itself is important in sensitization and hypersensitivity (e.g., in TMA hypersensitivity). IgE mediated activity is associated also with T-lymphocyte activity in the lung, as found from bronchoalveolar lavage (BAL) studies (Gerblich et al., 1991). There can also be IgG blocking antibody that somehow prevents IgE mediated reactions. (Secretory IgA is the most abundant immunoglobulin the lung, but its role in amplification-control of IgE is poorly understood. Turner-Warwick, 1978). Sensitization can occur in the lower respiratory tract, usually called hypersensitivity pneumonitis (or extrinsic allergic alveolitis), such as isocyanate disease. The nature of the protein-hapten deserves attention; T-and B-cells appear to have specific roles (Ibid.). Mediators (such as lymphokines) and receptors, and of other factors require further elucidation. Secretory IgA, along with IgG, and T-cells (especially suppressor/cytotoxic CD8 cells) are usually involved in hypersensitivity pneumonitis (Schlueter, 1982; Patterson et al., 1990, Semenzato, 1991). Some of the other known IgE-mediated chemical hypersensitivities are platinum and nickel salts, cobalt, other isocyanates (in addition to TDI), other anhydrides (in addition to TMA, such as phthalic acid anhydride), and organic acids (such as plicatic acid from red cedar) which are essentially all low molecular weight compounds which form protein haptens (Brooks, 1982; Marone, 1989; Allegra et al., 1989; Nemery, 1990, Chan-Yeung, 1990). Based on skin reactions, chromium salts, and colophony flux probably have IgE mediated immediate hyper-sensitivity. Based on this, and sensitization through ingestion, there are other chemicals, such as formaldehyde and ethylene oxide, which may turn out to have some IgE mediated hypersensitivity (Rockel et al., 1989). The various metals/metal salts appear to have IgG involvement also (as shown by precipitin formation), as do isocyanates and anhydrides (Adams et al, 1988; Thurmond and Dean, 1988; Patterson et al., 1990). Some of the haptens formed will produce late phase reactions as well, related to influxes of eosinophils, PMN's, inflammatory mediators (op cit.). Non-atopics will produce IgE

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