Allergy and Immunology · 3 min read
Immune System and Hypersensitivity
Classifying a reaction by mechanism predicts its timing, its tests and its treatment, and complement patterns are a favorite way to test immunology on the exam.
Innate and Adaptive Immunity
Innate immunity acts within minutes and is nonspecific: epithelial barriers, neutrophils, macrophages, natural killer cells, mast cells and complement. Adaptive immunity is antigen-specific and has memory. CD4+ helper T cells direct the response: Th1 cells (interferon-gamma) drive cellular immunity against intracellular pathogens, Th2 cells (interleukin [IL]-4, IL-5, IL-13) drive IgE production and eosinophils, and Th17 cells (IL-17) defend mucosal surfaces; regulatory T cells maintain tolerance. CD8+ cytotoxic T cells kill infected and malignant cells.
Gell and Coombs Classification
| Type | Mechanism | Timing | Examples |
|---|---|---|---|
| I (immediate) | Allergen cross-links IgE on mast cells and basophils | Minutes to 1–2 h | Anaphylaxis, urticaria, allergic rhinitis, allergic asthma |
| II (cytotoxic) | IgG or IgM against cell or matrix antigens | Hours to days | Autoimmune hemolytic anemia, anti-glomerular basement membrane disease, myasthenia gravis, Graves disease |
| III (immune complex) | Antigen-antibody complexes deposit and activate complement | 1–3 weeks after exposure | Serum sickness, lupus nephritis, poststreptococcal glomerulonephritis, cryoglobulinemic vasculitis |
| IV (delayed, T cell) | Sensitized T cells release cytokines or kill directly | 48–72 h or longer | Contact dermatitis, tuberculin test, severe and morbilliform drug eruptions |
Type IV reactions are now subdivided by the effector cell: IVa (macrophages; tuberculin test), IVb (eosinophils; drug reaction with eosinophilia and systemic symptoms [DRESS]), IVc (cytotoxic T cells; Stevens-Johnson syndrome and toxic epidermal necrolysis) and IVd (neutrophils; acute generalized exanthematous pustulosis). Serum sickness presents 1–3 weeks after a drug or antitoxin with fever, rash, arthralgias and low complement; a serum sickness-like reaction (e.g. cefaclor, amoxicillin) has similar symptoms without immune complexes or hypocomplementemia.
Complement
The classical pathway is triggered by antibody-antigen complexes (C1q, C4, C2), the lectin pathway by mannose-binding lectin on microbes, and the alternative pathway by spontaneous C3 activation on surfaces. All converge on C3, generating the opsonin C3b, the anaphylatoxins C3a and C5a, and the membrane attack complex (C5b–C9). C1 esterase inhibitor regulates the classical and contact (kallikrein-bradykinin) systems. The total hemolytic complement (CH50) screens the classical pathway; a near-zero CH50 suggests an inherited deficiency.
| C3 | C4 | Pattern suggests |
|---|---|---|
| Low | Low | Classical pathway consumption: active lupus, cryoglobulinemia (C4 often very low), serum sickness |
| Low | Normal | Alternative pathway: poststreptococcal glomerulonephritis, C3 glomerulopathy, atypical hemolytic uremic syndrome |
| Normal | Low | C1 inhibitor deficiency (hereditary or acquired angioedema) |
| Normal | Normal, CH50 near zero | Inherited deficiency of a single component (e.g. C5–C9) |
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