When antigen cross-links adjacent IgE–FcεRI complexes, the receptors cluster and their cytoplasmic tails are phosphorylated by Lyn and Syk, triggering a calcium flux and the fusion of pre-formed granules with the plasma membrane. This is degranulation, and it happens within minutes. The granule contents include histamine, which dilates local blood vessels, increases their permeability, and stimulates sensory nerve endings, producing the wheal, flare, itch, and sneeze of the early phase. Tryptase and other proteases are released alongside it. In parallel, the activated cell synthesizes lipid mediators from membrane arachidonic acid: prostaglandin D2 and leukotrienes, which prolong vasodilation and bronchoconstriction, and platelet-activating factor. Together these mediators account for the early-phase symptoms — urticaria, rhinorrhea, and in severe cases bronchospasm and hypotension.
The early phase fades over roughly thirty minutes, but in many reactions a second wave begins two to six hours later. This late phase is not caused by more granule release. The early mediators, particularly histamine and the chemokines released with them, recruit eosinophils, basophils, and additional Th2 cells into the tissue. Those recruited cells release their own mediators — eosinophil granule proteins, leukotrienes, and cytokines including IL-4, IL-5, and IL-13 — which sustain inflammation, damage local epithelium, and produce a more prolonged swelling and tissue dysfunction. The distinction matters because the two phases respond to different interventions: antihistamines blunt the early phase, while the late phase is driven by recruited cells and their products.