Hypersensitivity Reactions Overview

Hypersensitivity Reactions

• Hypersensitivity reactions are exaggerated immune responses to exogenous or endogenous (self) antigens.
• Antigens can include infections (bacterial, viral, fungal), harmless substances (animals' wool, drugs, plant pollens, metals, dust, foods like eggs, fruits, peanuts, seafood), and self-antigens (autoimmunity).
• Stages of hypersensitivity reactions include sensitization (asymptomatic first contact with an antigen) and effector (symptomatic phase during second and repeated exposures).

Types of Hypersensitivity

• There are four types of hypersensitivity reactions (ACID):
  • Type I (Allergy, atopy, or immediate hypersensitivity)
  • Type II (Cytotoxic hypersensitivity)
  • Type III (Immune complex hypersensitivity)
  • Type IV (Delayed or cell-mediated hypersensitivity)
• Types I, II, and III are antibody-mediated, while type IV is cell-mediated.

Type I Hypersensitivity (Immediate Hypersensitivity)

• Symptoms appear 15-30 minutes (or up to 6-24 hours) after allergen exposure.
• Type I is also known as allergy or atopy; it does not cause autoimmune diseases.
• Examples:
  • Localized reactions: urticaria, allergic rhinitis, asthma, allergic conjunctivitis.
  • Systemic reaction (anaphylaxis): low blood pressure and airway obstruction, can be fatal
• Mechanism (First exposure - Sensitization phase): Plasma cells produce specific IgE, which binds to Fce receptors on mast cells and basophils.
• Mechanism (Second and repeated exposure - Early reaction): Allergen binds to specific IgE on mast cells, leading to degranulation and release of inflammatory mediators (tryptase, histamine, prostaglandins).
  • Effects of mediators: itching, vasodilation, increased vascular permeability, edema, erythema, hypotension, contraction of bronchial and intestinal muscles. (early reaction).
• Mechanism (Late reaction): Attraction of eosinophils results in tissue damage.

Type II Hypersensitivity (Cytotoxic Hypersensitivity)

• This type leads to cell destruction.
• Antigens: Exogenous (drug bound to cell membrane) or Endogenous (part of cell membrane -- autoimmune disease).
• Mechanism: IgM or IgG bind to the cell membrane, leading to cell destruction through:
  • Opsonization and phagocytosis
  • Natural killer (NK) cell activation
  • Complement activation and cell lysis by MAC (membrane attack complex).
• Clinical examples:
  • Blood transfusion reaction (anti-A/B antibodies)
  • Hemolytic disease of the fetus and newborn (Rh incompatibility)
  • Autoimmune diseases (anti-acetylcholine receptor in myasthenia gravis, drug-induced autoimmune hemolytic anemia, like penicillin)

Type III Hypersensitivity (Immune Complex Hypersensitivity)

• Known as immune complex hypersensitivity.
• Soluble antigens form immune complexes.
• Antigens: Exogenous (drugs) or Endogenous (soluble self-antigen in autoimmune diseases).
• Mechanism: IgG antibodies bind to circulating antigens, forming immune complexes that deposit in tissues, especially blood vessels. They activate complement and neutrophils leading to inflammation (e.g., vasculitis).
• Clinical examples:
  • Arthus reaction (localized in skin, like from vaccines)
  • Serum sickness (systemic reaction from injected drugs)
  • Systemic lupus erythematosus (SLE) (antibodies against DNA, RNA, histones)

Type IV Hypersensitivity (Delayed or Cell-Mediated Hypersensitivity)

• This type is cell-mediated, peaking 48-72 hours after exposure to antigens.
• Antigens: Intracellular pathogens (e.g., mycobacteria, viruses), metals, chemicals, and self-antigens.
• Cells involved: CD4+ T helper-1 cells, macrophages, and CD8+ T cytotoxic cells.
• Mechanism: Sensitized Th1 cells release cytokines (like IFN-γ), attracting macrophages and activating them, or directly damaging cells.
• Clinical examples:
  • Contact dermatitis (e.g., nickel, cosmetics, plants like ivy)
  • Granulomatous formation (e.g., tuberculosis)
  • Tuberculin skin test
  • Some autoimmune diseases (e.g., type 1 diabetes, multiple sclerosis)
  • Drug-induced rash (e.g., after amoxicillin)