Indoor Allergens Assessing and Controlling Adverse Health Effects (1993) / Chapter Skim
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4 Mechanisms of Immune Function
4 Mechanisms of Immune Function
Pages 131-152
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From page 131... ...
Almost simultaneously, other observers noted similar responses in guinea pigs to widely spaced injections of nontoxic protein antigens. With the increasing use of horse and rabbit antisera to treat various infectious diseases in man, various adverse reactions due to the immune response soon became commonplace.
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From page 132... ...
The inhaled allergens then interact with IgE antibodies on the surface of mast cells in the mucosa to cause the release of histamine and other bioactive mediators. These mediators, in turn, cause vasodilation of blood vessels and stimulate secretory cells.
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From page 133... ...
age s Dendritic cells T cells B cells Mast cells Eosinophils Neutrophils Neuroepithelial cells APC, cytokines, mediators APC, cytokines, mediators Bronchial tone, cytokines, mediators Cytokines, mediators, growth factors APC, cytokines, mediators APC, cytokines, mediators Cytokines, specific response (TCR) APC, Ig production, mediators Cytokines, mediators, specific responses (IgE)
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From page 134... ...
These include fibroblasts; mast cells in a resting or basal, nonactivated state; nerve cells; and a rich biochemical network of ground substances including collagen, fibronectin, and other structural proteins and proteoglycans that contribute to the integrity of the airways. Within the bronchi, structural integ
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From page 135... ...
Moreover, once such a response has been evoked, there may be a further influx of immune and inflammatory cells to the airway. Immune and Inflammatory Cells in the Airway A wide variety of immune and inflammatory cells are involved in airway responses to inhaled proteins in the bronchi as well as in the upper and lower airways.
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From page 136... ...
FUNCTION The function of macrophages is to provide nonspecific as well as specific host defense in various tissues; these tissue macrophages can be resting or activated, depending on local conditions. The ability of macrophages to "process" extracellular proteins, including inhaled proteins taken from ambient inspired air and leached from particles, makes them primary airway defenders; they not only eliminate inhaled proteins but also act as allergenpresenting and allergen-processing cells (Unanue and Cerottini, 1989~.
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From page 137... ...
These substances include cytokines such as interleukin-1 (IL-1) , tumor necrosis factor, interferons of the alpha and gamma categories, protein-derived regulatory mediators such as fibronectin, transforming growth factor BIB, and plateletderived growth factor (Martin and Goodman, 19901.
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From page 138... ...
T CELL RECEPTORS On allergen-specific T cells, the presence of the CD3 marker is associated with coexpression of specific T cell receptors that are developed through molecular recombination events. These events can encompass the association and recombination of various gene segments involved in specific recognition of protein antigens in conjunction with self class II MHC molecules.
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From page 139... ...
The CD4 marker is important in another regard as well: it acts as a cofactor in recognizing immunogenic complexes of protein antigens in conjunction with class II MHC molecules. Thus, the subset of CD4+ T cells is the helper cells involved in the response to inhaled protein and, in particular, to inhaled allergens, triggering an allergic response (Robinson et al., 19921.
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From page 140... ...
The potential role of CD8+ T cells in regulating the response in the airway to inhaled proteins and allergens is not yet clear, but it is reasonable to assume that it involves limiting viral infection. In particular, it may involve limiting the potential damage that might result from inhaled allergenic proteins mediated by CD4+ TH2-type cells.
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From page 141... ...
B LYMPHOCYTES B lymphocytes, the other major population of lymphocytes, are also involved in the immune and inflammatory reaction that occurs in the airways. B lymphocytes are derived from bone marrow precursors that mature through development in the bone marrow and by exposure to microenvironmental milieus that include a number of growth- and development-related cytokines.
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From page 142... ...
Like the T and B lymphocytes and macrophages, mast cells are derived from bone marrow precursors that generate mature airway tissue cells with significant host defense capability. Mast cell development is influenced by various cytokines including granulocyte macrophage colonystimulating factor (GM CSF)
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From page 143... ...
In particular, the activation by an allergen of T lymphocytes, and possibly mast cells, will generate the cytokines required to evoke a strong eosinophil response in airway inflammation. NEUTROPHIES At one time, neutrophils were thought to be extremely important in stimulating the asthmatic, destructive airway response that is found in patients with asthma.
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From page 144... ...
Therefore, the contribution of neutrophils to airway inflammation and response to inhaled protein allergens should not be discounted (Boey et al., 19891. MEDIATORS Various kinds of mediators are derived from the immune and inflammatory cells discussed in the previous section and are important in the inflammatory response in the airways.
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From page 145... ...
Products of arachidonate metabolism, including both lip oxygenase and cyclooxygenase products, can be proinflammatory; such products may be mediators in activating other inflammatory cells at a site of inhaled protein antigen deposition. Reactive oxygen metabolites, which are products made by activated macrophages, neutrophils, and eosinophils, are another significant type of mediator, as are superoxide, peroxide, and hypochlorous acid all of these substances may contribute to an inflammatory response to inhaled allergens.
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From page 146... ...
The identification of IL-8 and other cytokines as chemotactic factors combined with our new understanding of cell adhesion and movement provides a useful framework for potential models of airway inflammatory cell recruitment in response to inhaled allergens. GENERATION OF IMMUNE RESPONSE AND HOST DEFENSE TO INDOOR ALLERGENS Nonspecific Mechanisms of Airway Host Defense Several significant nonspecific mechanisms of airway host defense may play a role in the response of the upper and lower airways to inhaled protein antigens, allergens, and/or particles (see Tables 4-3 and 4-4~.
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From page 147... ...
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.
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From page 149... ...
In addition to these mechanisms for pulmonary reactions to inhaled allergens, there are similar mechanisms for reactions at other tissue sites including the nose, the conjunctivae, and the skin. There are ever data to suggest that indoor allergens may play some role in generating allergic inflammation of the skin resembling atopic dermatitis.
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From page 150... ...
IL-3, IL-5, GM-CSF IL-1, tumor necrosis factor (TNF) IL-3, IL-4, IL-9, IL-10 hematopoietic stem cell factor Connective tissue activating peptide III, Neutrophil activating peptide 2, Macrophage chemotactic activating factor IFNy, GM-CSF, granulocyte-CSF, TNFs, IL-1, IL-4, IL-6, IL-8, platelet factor 4, macrophage inflammatory protein- 1, macrophage inflamatory protein-2, GM-CSF, TNFs, IL-1, IL-3, IL-5 IFNy, GM-CSF macrophage-CSF, TNFs, IL-1, IL-2, IL-3, IL-4 Eosinophilopoietins and activators Mast cell growth factors Histamine releasing factors Neutrophil-endothelial activating factors Eosinophil activating factors Macrophage activating factors NOTE: IL, interleukin; IFN, interferon; and GM-CSF, granulocyte macrophage colony-stimulating factor.
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From page 151... ...
Such a milieu will enhance the basic immunogenicity and allergenicity of inhaled proteins, which act as stimulants of the CD4+ T cell populations in a more standard immunological model. CONCLUSIONS AND RECOMMENDATIONS A great deal of knowledge has accumulated in the past 15 years concerning the role of inhaled proteins (including allergens)
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From page 152... ...
Research Agenda Item: Conduct research to identify risk factors other than exposure, and clarify their potential significance relative to indoor allergy. This effort should include an evaluation of the role of genetic and local host factors in allergen sensitization.
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