Type I Hypersensitivity (Immediate / IgE-Mediated)

Overview

Type I hypersensitivity is an immediate, IgE-mediated immune reaction that occurs within minutes of re-exposure to an allergen in a previously sensitized individual. It underlies conditions like anaphylaxis, allergic asthma, allergic rhinitis, urticaria, and atopic dermatitis.

Mechanism & Pathophysiology

Two-Phase Process

Phase 1 — Sensitization (First Exposure)

Antigen (allergen) is processed by antigen-presenting cells (APCs).
Th2 cells are activated → secrete IL-4, IL-5, IL-6, IL-10, IL-13.
A specialized subset, Tfh13 cells, produce IL-4, IL-5, and IL-13, driving allergen-specific IgE production by B cells.
IgE antibodies bind to high-affinity FcεRI receptors on mast cells (tissue) and basophils (blood) → cell becomes "armed."

(Harrison's, p. 9830)

Phase 2 — Re-Exposure (Elicitation)

Allergen cross-links two adjacent IgE–FcεRI complexes on the mast cell surface → degranulation.
Pre-formed and newly synthesized mediators are released.

Type I Hypersensitivity - IgE-mediated mast cell degranulation vs non-allergic pathway

Top: Classic IgE-mediated (Type I) — requires prior sensitization. Bottom: Non-allergic (pseudoallergic) — no prior sensitization needed.

Mediators Released

Mast cell/basophil mediators fall into three categories:

Category	Mediators	Effects
Preformed (granule)	Histamine, tryptase, heparin, TNF-α	Vasodilation, ↑ vascular permeability, bronchoconstriction, pruritus
Lipid-derived (newly synthesized)	Prostaglandins (PGD₂), Leukotrienes (LTC₄, LTD₄, LTE₄), PAF	Sustained bronchoconstriction, mucus secretion, chemotaxis
Cytokines	IL-4, IL-5, IL-13, TNF-α	Eosinophil recruitment, perpetuation of Th2 response

Phases of the Allergic Response

Phase	Timing	Mediators	Features
Early (immediate)	Minutes (0–30 min)	Histamine, tryptase	Wheal-and-flare, bronchospasm, pruritus
Late	4–12 hours later	Leukotrienes, cytokines, eosinophils	Sustained inflammation, tissue damage

Clinical Manifestations

Severity ranges from local to systemic:

Condition	Features
Anaphylaxis	Multisystem: urticaria, angioedema, bronchospasm, hypotension, cardiovascular collapse
Allergic asthma	Reversible bronchoconstriction, wheeze, dyspnea
Allergic rhinitis	Sneezing, rhinorrhea, nasal congestion, pruritus
Urticaria / Angioedema	Raised itchy wheals; deeper tissue swelling
Atopic dermatitis	Chronic eczematous inflammation
Allergic conjunctivitis	Tearing, conjunctival injection, itching
Food allergy	GI cramping, vomiting, systemic reactions

Diagnosis

Skin prick test (SPT): allergen introduced intradermally → wheal-and-flare within 15–20 min confirms sensitization.
Serum specific IgE (ImmunoCAP/RAST): measures allergen-specific IgE levels.
Serum total IgE: elevated in atopic individuals (less specific).
Serum tryptase: elevated after anaphylaxis; confirms mast cell activation.
Basophil activation test (BAT): flow cytometry-based; useful when SPT/specific IgE are inconclusive.

Management

1. Acute (Anaphylaxis)

Epinephrine IM (0.3–0.5 mg, 1:1000) — first-line; given into the anterolateral thigh.
IV fluids for hypotension.
H1 antihistamines (diphenhydramine) + H2 blockers — adjunctive only.
Corticosteroids (methylprednisolone) — adjunctive; prevent late-phase reaction.
Bronchodilators (salbutamol) for bronchospasm.
Patient should carry an auto-injector (EpiPen) after discharge.

2. Chronic / Prevention

Strategy	Examples
Allergen avoidance	Identify and eliminate triggers
H1 antihistamines	Cetirizine, loratadine, fexofenadine (2nd gen preferred)
Intranasal corticosteroids	Fluticasone, mometasone (allergic rhinitis)
Inhaled corticosteroids + LABA	Asthma control
Leukotriene receptor antagonists	Montelukast
Allergen immunotherapy (AIT)	Subcutaneous (SCIT) or sublingual (SLIT) — modifies disease course by shifting Th2 → Th1/Treg response
Biologics	Omalizumab (anti-IgE); dupilumab (anti-IL-4Rα) for severe asthma/atopic dermatitis

Key Comparison: Gell & Coombs Classification

Type	Mechanism	Timing	Example
I	IgE, mast cells, basophils	Minutes	Anaphylaxis, asthma
II	IgG/IgM + complement	Hours	Hemolytic transfusion reaction
III	Immune complexes	6–12 h	Serum sickness, SLE
IV	T-cell mediated (delayed)	48–72 h	Contact dermatitis, TB skin test

Summary: Type I hypersensitivity is a rapid, IgE-mediated reaction where allergen cross-linking of mast cell-bound IgE triggers degranulation and release of vasoactive, bronchospastic, and chemotactic mediators. Clinically it spans from mild local reactions to life-threatening anaphylaxis, with epinephrine as the cornerstone of acute treatment and immunotherapy as the only disease-modifying option. (Harrison's Principles of Internal Medicine, 21st Ed., p. 9830)

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