In individuals who are prone to allergies, exposure to some antigens results in the activation of Th2 cells and IL-4–secreting Tfh cells, and the production of IgE antibody (see Fig. 1). Most individuals do not mount strong Th2 responses to environmental antigens. For unknown reasons, when some individuals encounter certain antigens, such as proteins in pollen, certain foods, insect venoms, or animal dander, or if they are treated with certain drugs such as penicillin, there is a strong Th2 response. Immediate hypersensitivity develops as a consequence of the activation of Th2 and IL-4-secreting Tfh cells in response to protein antigens or chemicals that bind to proteins. Antigens that elicit immediate hypersensitivity (allergic) reactions often are called allergens.

Fig1. The sequence of events in immediate hypersensitivity. Immediate hypersensitivity reactions are initiated by the introduction of an allergen, which stimulates Th2 and IL-4/ IL-13–producing Tfh cells and immunoglobulin E (IgE) production. IgE binds to Fc receptors (FcεRI) on mast cells, and sub sequent exposure to the allergen activates the mast cells to secrete the mediators that are responsible for the pathologic reactions of immediate hypersensitivity.

Any atopic individual may be allergic to one or more of these antigens. It is not understood why only a small subset of common environmental antigens elicit T h2-mediated reactions and IgE production, or what characteristics of these antigens are responsible for their behavior as allergens.

In secondary lymphoid organs, IL-4 secreted by Tfh cells stimulates B lymphocytes to switch to IgE-producing plasma cells. Therefore, atopic individuals produce large amounts of IgE antibody in response to antigens that do not elicit IgE responses in other people. IL-4 and IL-13 secreted by Th2 cells induce some of the responses of tissues in allergic reactions, such as intestinal motility and excess mucus secretions. Th2 cells also secrete IL-5, which promotes eosinophilic inflammation that is characteristic of tissues affected by allergic diseases. Because the majority of Th2 cells migrate to peripheral tissues, whereas Tfh cells remain in secondary lymphoid organs, they likely serve different roles in allergic responses. Switching to IgE occurs mainly in the lymphoid organs and therefore helper function is provided by Tfh cells. Th2 cells may contribute to any isotype switching that occurs in peripheral sites of allergic reactions, and, more importantly, are responsible for inflammation and eosinophil activation at these sites.

The propensity toward differentiation of IL-4 and IL-5 producing T cells, and resulting atopic diseases such as asthma, has a strong genetic basis. A major known risk for developing allergies is a family history of atopic disease, and gene association studies indicate that many different genes play contributory roles. Some of these genes encode cytokines or receptors known to be involved in T and B lymphocyte responses, including IL-4, IL-5, and IL-13, and IL-4 receptor; how these gene variants contribute to atopic diseases is not known. Mutations of filaggrin, a protein required for barrier function of skin, increases risk for atopic dermatitis in early child hood, and subsequent allergic diseases including asthma.

Various environmental factors besides expo sure to allergens, including air pollution and expo sure to microbes, have a profound influence on the propensity to develop allergies, and this may be one reason why the incidence of allergic diseases, especially asthma, is increasing in industrialized societies. 

مواضيع ذات صلة

Hypersensitivity Disorders Caused by Immune Responses : Clinical Syndromes and Therapy

Activation of Mast Cells and Secretion of Mediators

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Monocytes–Macrophages: Host Defense Functions: Phagocytosis

Mononuclear Phagocyte System

Immune Mechanisms of Graft Rejection

Induction of Immune Responses Against Transplants

Transplantation Antigens

Glycans and Immunity

Immune Responses Against Transplants

Cancer Immunotherapy : Stimulation of Host Antitumor Immune Responses by Vaccination With Tumor Antigens