type I hypersensitivity

Type I hypersensitivity involves a two-phase process: sensitization and effector phase. During sensitization, an allergen is processed by antigen-presenting cells and presented to naive CD4+ T cells, which differentiate into Th2 cells. Th2 cells secrete IL-4 and IL-13, promoting B cell class switching to produce allergen-specific IgE. This IgE binds to high-affinity FcεRI receptors on mast cells and basophils, 'arming' them. Upon subsequent re-exposure to the same allergen, cross-linking of the cell-bound IgE by the antigen triggers immediate degranulation, releasing preformed mediators (histamine, tryptase, heparin) within minutes, causing the immediate phase reaction: vasodilation, increased vascular permeability, smooth muscle contraction, and mucus secretion. This is followed 4-6 hours later by a late-phase reaction driven by newly synthesized mediators (leukotrienes, prostaglandins, cytokines like IL-5) and recruitment of eosinophils, neutrophils, and Th2 cells, causing sustained inflammation.

Clinical examples include anaphylaxis (systemic, life-threatening, can involve airway edema and cardiovascular collapse), allergic rhinitis (hay fever), extrinsic asthma, atopic dermatitis, urticaria/angioedema, and food or drug allergies (e.g., penicillin allergy). Skin prick testing and serum-specific IgE (RAST) are used diagnostically. Treatment includes antihistamines, corticosteroids, and epinephrine for severe reactions (anaphylaxis) — epinephrine acts via alpha-1 (vasoconstriction), beta-1 (increased cardiac output), and beta-2 (bronchodilation, decreased mediator release) receptors. Mast cell stabilizers (cromolyn) and leukotriene receptor antagonists (montelukast) are used for chronic management. Understanding the IgE-mast cell axis is essential for USMLE questions distinguishing this from other hypersensitivity types (II: cytotoxic, III: immune complex, IV: delayed T cell-mediated).