Hypersensitivity, Complement & Autoimmunity
The four hypersensitivity reactions, autoimmune diseases, and transplant rejection types.
Interactive Diagram
Tap a teal label to learn about each structure.
Gell and Coombs Hypersensitivity
Type I is immediate, IgE-mediated mast cell degranulation (anaphylaxis, asthma, hay fever); onset minutes. Type II is antibody against fixed cell antigens causing complement lysis or opsonization (transfusion mismatch, autoimmune hemolytic anemia, Goodpasture syndrome, Graves). Type III is immune-complex deposition causing vasculitis and glomerulonephritis (SLE, post-streptococcal glomerulonephritis, serum sickness, polyarteritis nodosa). Type IV is delayed, T-cell mediated, peaking 48–72 hours (tuberculin PPD, contact dermatitis, granulomatous disease, transplant rejection). Knowing the mechanism predicts the timing and the tissue.
Type I Allergy in Depth
Sensitization: B cells class-switch to IgE driven by Th2 (IL-4/13); IgE binds FcεRI on mast cells and basophils. Re-exposure cross-links IgE, triggering degranulation of histamine, leukotrienes (LTC4/D4/E4), prostaglandins, and platelet-activating factor. Clinically: urticaria, bronchospasm, rhinitis, GI symptoms, anaphylactic shock. Diagnosis by skin prick and serum specific IgE. Treatment: avoidance, antihistamines, epinephrine for anaphylaxis, corticosteroids, and omalizumab (anti-IgE) or allergen immunotherapy.
Type II and Type III Examples
Type II: hemolytic disease of the newborn (anti-Rh), autoimmune hemolytic anemia (Coombs positive), immune thrombocytopenia, Goodpasture (anti-basement membrane — hemoptysis and glomerulonephritis), Myasthenia gravis (anti-AChR), Graves (anti-TSH receptor stimulating). Type III: SLE (anti-dsDNA complexes in glomeruli), rheumatoid factor complexes, post-streptococcal glomerulonephritis, polyarteritis nodosa (HBV-associated), serum sickness from foreign proteins or drugs.
Type IV: Cell-Mediated
Type IV reactions are mediated by CD4 (Th1) and CD8 T cells and macrophages, not antibody. The tuberculin skin test (PPD) and contact dermatitis (poison ivy, nickel) are prototypical. Granuloma formation in TB and sarcoidosis is a type IV process. Acute transplant rejection is type IV (T cells against donor MHC). This is why corticosteroids and calcineurin inhibitors (cyclosporine, tacrolimus) — which target T cells — are the mainstay of transplant immunosuppression.
Autoimmunity and Transplant
Autoimmunity arises from loss of tolerance with genetic susceptibility (HLA associations) plus environmental triggers. SLE (anti-dsDNA, anti-Sm; ANA screening; malar rash, nephritis), rheumatoid arthritis (anti-CCP, RF; symmetric small-joint synovitis), Hashimoto/thyroiditis (anti-TPO), type 1 diabetes (anti-islet), multiple sclerosis (anti-myelin). Transplant rejection types: hyperacute (preformed anti-donor antibody, minutes), acute (T-cell, days–weeks), chronic (indolent vascular fibrosis, months–years). Graft-versus-host disease occurs after hematopoietic stem-cell transplant when donor T cells attack host tissues.
