IgE synthesis is dependent on the activation of CD4+ helper T cells of the TH2 subset and their secretion of IL-4 and IL-13. It is likely that dendritic cells in epithelia through which allergens enter capture the antigens, transport them to draining lymph nodes, process them, and present peptides to naive CD4+ T cells. The T cells then differentiate into TH2 cells and into follicular helper T (Tfh) cells that secrete TH2 cytokines. The major factors that drive differentiation of TH2 cells are cytokines, especially IL-4, which may be produced by various cell types (see Chapter 9). In addition, the cytokine thymic stromal lymphopoietin, secreted by epithelial cells in the skin, gut, and lungs, enhances the ability of tissue dendritic cells to promote TH2 differentiation. TH2 and TFH cells then induce B cell switching to IgE through the actions of CD40 ligand and the cytokines IL-4 and IL-13.
Th2 cells are involved in other components of the immediate hypersensitivity reaction in addition to promotion of switching to IgE. IL-5 secreted by TH2 cells activates eosinophils, a cell type that is abundant in many immediate hypersensitivity reactions. IL-13 stimulates epithelial cells (e.g., in the airways) to secrete increased amounts of mucus, and excessive mucus production is also a common feature of these reactions. TH2 cells also contribute to the inflammation of the late-phase reaction, described later.
Consistent with a central role of TH2 cells in immediate hypersensitivity, larger numbers of allergen-specific IL-4-secreting T cells are found in the blood of atopic individuals than of nonatopic persons. In atopic patients, the allergen-specific T cells also produce more IL-4 per cell than in normal individuals. In animal models, a disease resembling human asthma can be induced by generation of TH2 cells specific for an inhaled antigen or by adoptive transfer of these cells into naive mice. Accumulations of TH2 cells are found at sites of immediate hypersensitivity reactions in the skin and bronchial mucosa.
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If you suffer with asthma, you will no doubt be familiar with the uncomfortable sensations as your bronchial tubes begin to narrow and your muscles around them start to tighten. A sticky mucus known as phlegm begins to produce and increase within your bronchial tubes and you begin to wheeze, cough and struggle to breathe.