Fig. 14.12The route of administration of allergen determines the type of IgE-mediated allergic reaction that results. There are two main anatomical distributions of mast cells: those associated with vascularized connective tissues and called connective tissue mast cells (MCCT), and those found in submucosal layers of the gut and respiratory tract and called mucosal mast cells (MCC). In an allergic individual, all of these mast cells are coated through their cell-surface Fcε receptors with IgE directed against specific allergens. The response to an allergen then depends on which mast cells are activated. Allergen in the bloodstream (intravenous) activates connective tissue mast cells throughout the body, resulting in the systemic release of histamine and other mediators. Entry of allergen through the skin activates local connective tissue mast cells, leading to a local inflammatory reaction. After an experimental skin
Allergic rhinitis (upper airway), Contraction of intestinal smooth muscle caused by increased mucus induces vomiting. Outfow of fuid into production and nasal irritation. gut causes diarrhea. Antigen diffuses
Asthma (lower airway) due to into blood vessels and is widely contraction of bronchial smooth muscle disseminated, causing urticaria (hives), and increased mucus secretion anaphylaxis, or atopic eczema prick with allergen or bite from an insect to which the individual is sensitized, this manifests as a wheal-and-flare reaction. In atopic individuals, airborne or topically applied allergens that penetrate the skin may lead to atopic eczema. Inhaled allergen that penetrates respiratory mucosal epithelia activates mainly mucosal mast cells, causing increased secretion of mucus by the mucosal epithelium and irritation in the nasal mucosa, leading to allergic rhinitis—or to asthma if constriction of smooth muscle in the lower airways occurs. Ingested allergen penetrates the gut epithelium, causing vomiting due to intestinal smooth muscle contraction and diarrhea due to outflow of fluid across the gut epithelium. Food allergens can also be disseminated in the bloodstream, causing widespread urticaria (hives) when the allergen reaches the skin, or they may cause eczema.
against either the α chain of FcεRI or against IgE itself, and thus can be considered a form of autoimmunity. Interaction of the autoantibody with the receptor triggers mast-cell degranulation, with resulting urticaria. In some patients, treatment with omalizumab (a therapeutic monoclonal anti-IgE antibody) leads to resolution of hives, demonstrating a role for IgE in these individuals, even though the antigen that elicited the IgE often cannot be identified.
In anaphylactic shock, a widespread increase in vascular permeability and smooth muscle contraction results from a massive release of histamine and other mast celland basophil-derived mediators such as leukotrienes.
The consequences are a catastrophic reduction of blood pressure, culminating in hypotensive shock, (a condition in which low blood pressure leads to inadequate supply of blood to vital organs, often leading to death), and constriction of the airways, culminating in respiratory failure. The most common causes of anaphylaxis are allergic reactions to wasp and bee stings, ingested or injected medications, or allergic responses to foods in sensitized individuals. For example, anaphylaxis in individuals allergic to peanuts is relatively common. Severe anaphylactic shock can be rapidly fatal if untreated, but can usually be controlled by the immediate injection of epinephrine, which via stimulation of β-adrenergic receptors causes relaxation of airway smooth muscles, and via stimulation of α-adrenergic receptors reverses the life-threatening cardiovascular effects.