Hypersensitivity Reactions

Hypersensitivity Intro - Immune Overdrive

• Definition: Exaggerated immune response to an antigen (allergen), causing inflammation and host tissue damage.
• Gell & Coombs Classification (1963): Divides reactions into four main types. 📌 ACID

  Type	Name (ACID)	Key Mediator(s)
  Type I	Allergic	IgE, mast cells
  Type II	Cytotoxic	IgG/IgM (vs cell Ag)
  Type III	Immune Complex	IgG/IgM complexes, complement
  Type IV	Delayed-type	T-lymphocytes

⭐ Gell and Coombs classification (1963) is based on the primary mechanism of immune-mediated injury.

Type I Rxns - Allergic Alarms

📌 Mnemonic: 'First and Fast' (ACID: Allergic)

• Mediator: IgE antibodies produced by plasma cells.

• Key Cells: Mast cells (tissue) and basophils (circulation).

• Key Chemical Mediators:

  • Pre-formed: Histamine, proteases (e.g., tryptase).
  • Newly synthesized: Leukotrienes ($LTC_4, LTD_4, LTE_4$), prostaglandins ($PGD_2$), cytokines.

• Onset: Immediate, typically within minutes of allergen re-exposure.

• Mechanism:

• Clinical Examples: Anaphylaxis, Allergic Asthma, Hay fever (Allergic Rhinitis), Urticaria (hives), Atopic Eczema.

⭐ Type I hypersensitivity involves IgE antibodies coating mast cells; re-exposure to the allergen causes rapid degranulation and release of histamine and other potent mediators.

Type II Rxns - Cytotoxic Chaos

📌 Cy-2-toxic IgG/IgM antibodies target cell surface or extracellular matrix antigens, causing damage.

• Mechanisms & Examples:
  • Opsonization & Phagocytosis: Cells coated with Ab/C3b are phagocytosed. E.g., Autoimmune hemolytic anemia (AIHA), Idiopathic Thrombocytopenic Purpura (ITP).
  • Complement-mediated Lysis/Inflammation: Ab activates complement → MAC formation & inflammation. E.g., Goodpasture's syndrome, Rheumatic fever.
  • Antibody-Dependent Cell-mediated Cytotoxicity (ADCC): NK cells bind Fc of Ab on target cell → lysis.
  • Antibody-mediated Cellular Dysfunction:
    • Receptor antagonism: Myasthenia Gravis (anti-AChR).
    • Receptor agonism: Graves' disease (anti-TSHR).
    • Blocking vital molecules: Pernicious anemia (anti-Intrinsic Factor).

⭐ Goodpasture syndrome involves antibodies against Type IV collagen (specifically the alpha-3 chain) in glomerular and alveolar basement membranes.

Type III Rxns - Immune Complex Clutter

• Mediator: Soluble Antigen-Antibody (Ag-Ab) immune complexes (ICs); primarily IgG, also IgM.
• Mechanism: "Complexes Clutter & Cause Chaos"
  • ICs form in circulation (Ag excess) & deposit in tissues (e.g., vessel walls, glomeruli, joints, skin).
  • Complement system activation (classical pathway: C3a, C5a anaphylatoxins) → ↑vascular permeability, neutrophil chemotaxis.
  • Recruited neutrophils release lysosomal enzymes & Reactive Oxygen Species (ROS) → tissue damage (e.g., vasculitis, glomerulonephritis, arthritis).
• 📌 Mnemonic: 3 things make a complex (Antigen, Antibody, Complement).

⭐ Serum sickness (systemic) and Arthus reaction (local) are classic examples of Type III hypersensitivity.

Type IV Rxns - Delayed Drama

• Mediators: T-lymphocytes (CD4+ Th1/Th17, CD8+ CTLs).
• Mechanism: Sensitized T-cells → cytokines → macrophage activation OR direct T-cell cytotoxicity.
• Onset: Delayed (24-72 hours). 📌 Mnemonic: "4 T's: T-cells, Transplant rejection, TB skin test, Touching (contact dermatitis)".
• Examples:
  • CD4+ (Cytokine-mediated):
    • Contact dermatitis (poison ivy).
    • Tuberculin test (Mantoux): Induration ≥15mm (immunocompetent).
    • Granulomas (TB, sarcoidosis).
  • CD8+ (Direct cytotoxicity):
    • Type 1 Diabetes.
    • Multiple Sclerosis.
    • Hashimoto's thyroiditis.
    • Graft rejection.

⭐ The Mantoux test for tuberculosis is a classic example of a delayed-type hypersensitivity (DTH) reaction.

High‑Yield Points - ⚡ Biggest Takeaways

• Type I (Anaphylactic): IgE-mediated; mast cell degranulation. Examples: anaphylaxis, allergic asthma.
• Type II (Cytotoxic): Antibody (IgG/IgM)-mediated destruction of cells/tissues. Examples: Goodpasture's syndrome, AIHA.
• Type III (Immune Complex): Deposition of circulating antigen-antibody complexes. Examples: SLE, PSGN, serum sickness.
• Type IV (Delayed-Type): Cell-mediated immunity (sensitized T-lymphocytes). Examples: contact dermatitis, tuberculin PPD test.
• Arthus reaction is a localized Type III; Serum sickness is systemic Type III.
• Remember Gell and Coombs classification (Types I-IV).