Quick Answer
Allergic reactions are classified into four types by the Gell and Coombs system. Type I reactions are IgE-mediated and immediate (classic allergy). Type II involves antibodies attacking cells. Type III involves immune complexes. Type IV is T-cell-mediated and delayed, as in contact dermatitis. Most common allergy is Type I.
Type I: Immediate IgE-Mediated Hypersensitivity
Type I hypersensitivity is what most people mean when they say 'allergy.' It involves allergen-specific IgE antibodies bound to mast cells and basophils. Within seconds to minutes of allergen re-exposure, IgE crosslinking triggers mast cell degranulation, releasing histamine, tryptase, leukotrienes, and prostaglandins. Symptoms include urticaria, rhinitis, conjunctivitis, angioedema, asthma, and anaphylaxis.
Type I reactions are diagnosed by skin prick testing and specific IgE blood tests. Common causes include foods (peanuts, shellfish, milk), environmental allergens (pollen, dust mites, pet dander), insect venom, latex, and medications. Anaphylaxis — the most severe Type I reaction — requires immediate epinephrine treatment.
Type II and Type III: Antibody-Mediated Reactions
Type II hypersensitivity involves IgG or IgM antibodies that bind directly to cell surfaces or tissue antigens, activating complement and causing cell destruction. Examples relevant to allergic disease include drug reactions where a medication binds to red blood cells and triggers their destruction (hemolytic anemia). Goodpasture syndrome and some transfusion reactions are Type II.
Type III hypersensitivity involves immune complex formation — IgG antibodies binding to circulating antigens and forming complexes that deposit in tissues, activating complement. Serum sickness (from heterologous antisera) and some drug reactions are examples. Type III reactions cause symptoms 1–3 weeks after exposure, unlike the immediate Type I response.
Type IV: Delayed T-Cell-Mediated Hypersensitivity
Type IV hypersensitivity is fundamentally different from the IgE-mediated allergy: it involves T lymphocytes rather than antibodies and produces reactions that peak 48–72 hours after exposure. Allergic contact dermatitis — from nickel jewelry, poison ivy, latex gloves, fragrances, or preservatives — is the most common Type IV reaction in clinical practice.
During Type IV sensitization, antigen-presenting cells present hapten-protein complexes to naive T cells in lymph nodes, generating memory effector T cells. On re-exposure, these memory T cells accumulate in the skin at the contact site, release inflammatory cytokines, and recruit macrophages — producing the characteristic itchy, weeping rash that appears 24–72 hours after contact.
Patch testing — not skin prick testing — is used to diagnose Type IV contact allergy. A panel of 30–70 standardized contact allergens is applied under adhesive patches for 48 hours, and reactions are read at 48 and 96 hours. Treatment involves identifying and avoiding the causative allergen plus topical corticosteroids for active dermatitis.
Mixed and Pseudoallergic Reactions
Some reactions do not fit neatly into the Gell and Coombs classification. Aspirin and NSAID hypersensitivity can cause urticaria and anaphylaxis through non-IgE mechanisms by inhibiting cyclooxygenase and diverting arachidonic acid into the leukotriene pathway. Radiocontrast media reactions occur through direct mast cell activation without IgE. These are called pseudoallergic or anaphylactoid reactions — clinically similar to Type I but managed differently.
Key Takeaways
- Type I (IgE-mediated, immediate): classic allergy — urticaria, rhinitis, anaphylaxis.
- Type II (antibody-mediated): IgG/IgM attacks cells — drug-induced hemolysis.
- Type III (immune complex): complement activation from deposited complexes — serum sickness.
- Type IV (T-cell-mediated, delayed): contact dermatitis peaking at 48–72 hours — diagnosed by patch test.
- NSAID reactions and contrast dye reactions are pseudoallergic (non-IgE) but can mimic anaphylaxis.
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