Hypersensitivity Reaction


Hypersensitivity Reaction, Hypersensitivity, Gell and Coombs Classification, Coombs and Gell Classification, Type 1 Hypersensitivity, Immediate Hypersensitivity Reaction, Type 2 Hypersensitivity, Cytotoxic Antibody Reaction, Type 3 Hypersensitivity, Immune Complex Reaction, Type 4 Hypersensitivity, Delayed-Type Hypersensitivity, Stimulatory Hypersensitivity, Immune Hypersensitivity Reaction

  • Definitions
  1. Hypersensitivity
    1. Immune System sensitization after repeated allergan exposure
  2. Allergen
    1. Exogenous Antigens (typically proteins) that trigger an immune response
  3. Gell and Coombs Classification of Hypersensitivity Reaction
    1. Categories of Hypersensitivity Response
  • Types
  • 1 - Immediate Hypersensitivity Reaction
  1. Immediate allergan immune response after repeated exposure (esp. in Atopic Patients)
  2. Mediated by IgE Antibody to specific Antigens
    1. Sensitization
      1. B-Cells are are exposed to Antigen
      2. T-Helper Cells (TH2) bind to B-Cells
      3. B-Cells class switch to produce IgE Antibody against Antigen (instead of IgG and IgM)
      4. B-Cells produce the IgE against the specific Antigen
      5. IgE binds Mast Cells at the high affinity receptor (FceRI)
      6. Mast Cells are now sensitized, awaiting allergan reexposure
    2. Mast Cells are then stimulated with repeat exposure
      1. Release secretory granules including histamine (as well as leukotrienes, prostaglandins)
      2. Although there are four histamine receptors (H1, H2, H3, H4), H1 predominates in Type I Reaction
  3. Reaction Phases
    1. Early Phase (within minutes of exposure, <1 hour)
      1. Histamine-induced vasodilation, edema, congestion
    2. Late Phase (2 to 24 hours after exposure)
      1. Inflammatory cell infiltration (Eosinophils, Neutrophils, T-Cells)
  4. Examples
    1. Anaphylaxis (e.g. Penicillin)
    2. Urticaria
    3. Angioedema
    4. Anaphylactoid Reaction (e.g. Anaphylactoid Reaction to Radiocontrast)
    5. Atopic Allergy (e.g. Allergic Rhinitis, Allergic Asthma)
    6. Food Allergy
    7. Bee sting Allergy
    8. Allergic Occupational Asthma
  • Types
  • 2 - Cytotoxic Antibody Reaction (non-IgE Antibody Mediated Reaction)
  1. Mediated by IgG and IgM (on cell surface or extracellular complex) to specific Antigens
  2. Antibody-Antigen Complex destruction by one of three mechanisms
    1. Opsonization and Phagocytosis
      1. Antibody-bound Antigen (Opsonin) is destroyed by cells (PMNs, Macrophages) engulfing complex (Phagocytosis)
    2. Antibody-dependent cellular cytotoxicity (ADCC)
      1. Antibodies bind infected cells with surface Antigen, targeted for Natural Killer Cell-mediated destruction
    3. Complement Activation
      1. IgG binds Antigen and activates complement
      2. Antibody-Antigen complexes by lysis or phagocytocsis
  3. Examples
    1. Transfusion Reaction (ABO Incompatibility)
    2. Rhesus Incompatibility (Rh Incompatibility, Autoimmune Hemolytic Anemia)
    3. Mycoplasma pneumoniae related cold agglutinins
    4. Autoimmune Thrombocytic Purpura
    5. Hashimoto's Thyroiditis
    6. Grave's Disease
    7. Goodpasture's Syndrome
    8. Delayed transplant Graft Rejection
    9. Myasthenia Gravis
  • Types
  • 3 - Immune Complex Reaction
  1. Antigen-Antibody immune complexes deposit in tissue
    1. Most immune complexes activate complement system and are destroyed by phagocytic cells (PMNs, Macrophages)
    2. However, small complexes may be missed by Phagocytosis, and instead deposit in tissue
  2. Small immune complex deposition results in inflammatory reaction within 1-3 weeks of exposure
    1. Blood vessel walls resulting in Vasculitis
    2. Renal glomerular basement membrane resulting in nephritis
    3. Joint synovial membranes resulting in Arthritis
  3. Examples
    1. Serum Sickness (prototypical Immune Complex Reaction)
    2. Systemic Lupus Erythematosus
    3. Erythema Nodosum
    4. Polyarteritis Nodosa
    5. Arthus Reaction (e.g. Farmer's Lung)
    6. Rheumatoid Arthritis
    7. Elephantiasis (Wuchereria bancrofti reaction)
    8. Jarisch-Herxheimer Reaction
  • Types
  • 4 - Delayed-Type Hypersensitivity (Cell-Mediated)
  1. Reaction within 2-7 days after exposure
  2. Mediated by Effector T Lymphocytes (CD4+ and CD8+), activated in response to specific Antigens
    1. Antigen bound to Major Histocompatibility Complex (MHC) on Antigen Presenting Cells
    2. Activated T Lymphocytes release Cytokines (e.g. Interferon-gamma) and CD8+ cells may destroy Antigen directly
    3. Cytokines trigger Phagocytosis and inflammation
  3. Examples
    1. Allergic Contact Dermatitis (e.g. Nickel allergy)
    2. Mantoux Test (PPD)
      1. Immune Allergic Contact Dermatitis after prior Mycobacterium tuberculosis exposure
  • Types
  • Other allergy mediated reactions
  1. Stimulatory Hypersensitivity
    1. Humoral Antibody activates receptor sites
    2. Example: Thyrotoxicosis (TSH autoantibodies)
  2. Fas/Fas Ligand-induced apoptosis
    1. Example: Stevens Johnson Syndrome
  3. T-Cell Activation
    1. Example: Sulfonamide induced Morbilliform rash
  • References
  1. Mahmoudi (2014) Immunology Made Ridiculously Simple, MedMaster, Miami, FL
  2. Roitt (1988) Essential Immunology, Blackwell,p. 193-214
  3. Riedl (2003) Am Fam Physician 68:1781-90 [PubMed]