immunology allergic disorders
Overview of Allergic and Atopic Disorders
Pathophysiology of Allergic and Atopic Disorders
When allergen binds to IgE-sensitized mast cells and basophils, histamine is released from their intracellular granules. Mast cells are widely distributed but are most concentrated in skin, lungs, and gastrointestinal (GI) mucosa; histamine facilitates inflammation and is the primary mediator of clinical atopy. Physical disruption of tissue and various substances (eg, tissue irritants, opiates, surface-active agents, complement components C3a and C5a) can trigger histamine release directly, independent of IgE. Histamine causes the following: Local vasodilation (causing erythema) Increased capillary permeability and edema (producing a wheal) Vasodilation of surrounding arterioles mediated by neuronal reflex mechanisms (causing flare—the redness around a wheal) Stimulation of sensory nerves (causing itching) Smooth muscle contraction in the airways (bronchoconstriction) and in the GI tract (increasing GI motility) Increased nasal, salivary, and bronchial gland secretions When released systemically, histamine is a potent arteriolar dilator and can cause extensive peripheral pooling of blood and hypotension; cerebral vasodilation may be a factor in vascular headache. Histamine increases capillary permeability; the resulting loss of plasma and plasma proteins from the vascular space can worsen circulatory shock. This loss triggers a compensatory catecholamine surge from adrenal chromaffin cells. 