reaction is due to IgE-mediated mast-cell activation and starts within seconds of allergen exposure. It is the result of the actions of histamine, prostaglandins, and other preformed or rapidly synthesized mediators released by mast cells. These mediators cause a rapid increase in vascular permeability, resulting in visible edema and reddening of the skin (in a skin response) and airway narrowing as result of edema and the constriction of smooth muscle (in an airway response). In the skin, histamine acting on H1 receptors on local blood vessels causes an immediate increase in vascular permeability, which leads to extravasation of fluid and edema. Histamine also acts on H1 receptors on local nerve endings, leading to reflex vasodilation of cutaneous blood vessels and local reddening of the skin. The resulting skin lesion is called a wheal-andflare reaction (see Fig. 14.11, right panel).
Whether a late-phase reaction occurs depends on allergen dose and on aspects of the cellular immune activation that are difficult to quantify. At doses of intradermally administered allergen that are deemed safe for skin testing of subjects with allergic asthma, for example, a late reaction occurs in about 50% of individuals who show an immediate response (see Fig. 14.11, right panel). The late reaction peaks between 3 and 9 hours after antigen challenge, and in skin tests becomes obvious as a much increased area and degree of edema (see Fig. 14.11, right panel) that can persist for 24 hours or longer. The late-phase reaction is caused by the continued synthesis and release of inflammatory mediators by mast cells, especially vasoactive mediators such as calcitonin gene-related peptide (CGRP) and vascular endothelial growth factor (VEGF), which cause vasodilation and vascular leakage that result in edema and the recruitment of eosinophils, basophils, monocytes, and lymphocytes. The importance of this cellular influx is shown by the ability of glucocorticoid medications to block the late-phase response through their inhibition of cell recruitment, whereas glucocorticoids do not block the immediate response. A late-phase reaction can also occur after aerosol exposure to allergen, and is characterized by a second phase of airway narrowing with sustained edema and cellular infiltration into the peribronchial spaces (see Fig. 14.11, left panel).
In patients with a clinical history of allergic disease, allergists use the immediate response to help assess and confirm sensitization, and to determine which allergens are responsible. Minute amounts of potential allergens are introduced into the skin by a skin prick—one site for each allergen—and if the individual is sensitive to any of the allergens tested, a wheal-and-flare reaction will occur at the site within a few minutes (see Fig. 14.11, right panel). Although the reaction after the administration of such small amounts of allergen is usually very localized, there is a small risk of inducing anaphylaxis. Another standard test for allergy is to measure the circulating concentration of IgE antibody specific for a particular allergen in a sandwich ELISA (see Appendix I, Section A-4).