19.1 Hypersensitivities  (Page 2/24)

For susceptible individuals, a first exposure to an allergen activates a strong T _H 2 cell response ( [link] ). Cytokines interleukin (IL)-4 and IL-13 from the T _H 2 cells activate B cells specific to the same allergen, resulting in clonal proliferation, differentiation into plasma cells, and antibody-class switch from production of IgM to production of IgE . The fragment crystallizable (Fc) regions of the IgE antibodies bind to specific receptors on the surface of mast cells throughout the body. It is estimated that each mast cell can bind up to 500,000 IgE molecules, with each IgE molecule having two allergen-specific fragment antigen-binding (Fab) sites available for binding allergen on subsequent exposures. By the time this occurs, the allergen is often no longer present and there is no allergic reaction, but the mast cells are primed for a subsequent exposure and the individual is sensitized to the allergen.

On subsequent exposure, allergens bind to multiple IgE molecules on mast cells, cross-linking the IgE molecules. Within minutes, this cross-linking of IgE activates the mast cells and triggers degranulation , a reaction in which the contents of the granules in the mast cell are released into the extracellular environment. Preformed components that are released from granules include histamine , serotonin , and bradykinin ( [link] ). The activated mast cells also release newly formed lipid mediators ( leukotrienes and prostaglandins from membrane arachadonic acid metabolism) and cytokines such as tumor necrosis factor ( [link] ).

The chemical mediators released by mast cells collectively cause the inflammation and signs and symptoms associated with type I hypersensitivity reactions. Histamine stimulates mucus secretion in nasal passages and tear formation from lacrimal glands, promoting the runny nose and watery eyes of allergies. Interaction of histamine with nerve endings causes itching and sneezing. The vasodilation caused by several of the mediators can result in hives, headaches, angioedema (swelling that often affects the lips, throat, and tongue), and hypotension (low blood pressure). Bronchiole constriction caused by some of the chemical mediators leads to wheezing, dyspnea (difficulty breathing), coughing, and, in more severe cases, cyanosis (bluish color to the skin or mucous membranes). Vomiting can result from stimulation of the vomiting center in the cerebellum by histamine and serotonin. Histamine can also cause relaxation of intestinal smooth muscles and diarrhea.