Type I Hypersensitivity

• Hypersensitivity refers to excessive, undesirable reactions produced by the normal immune system
• Hypersensitivity reactions require a pre-sensitized (immune) state of the host
• Hypersensitivity reactions are classified into four types (I, II, III, and IV) based on the mechanisms involved and the time course of the reaction

Type I Hypersensitivity

• Known as immediate or allergic hypersensitivity

• Mediated by IgE antibodies

• Antigens that trigger this are called allergens

• The mechanism involves sensitization:

  • Initial allergen exposure leads to IgE antibody production
  • IgE binds to FcεRI receptors on mast cells and basophils

• Activation:

  • Subsequent exposure to the allergen cross-links bound IgE on mast cells and basophils
  • This leads to degranulation and mediator release

• Mediators released:

  • Histamine causes vasodilation, increased vascular permeability, and bronchoconstriction
  • Leukotrienes have similar effects to histamine, but are more potent and longer-lasting
  • Prostaglandins contribute to inflammation and bronchoconstriction
  • Cytokines, such as IL-4 and IL-13, promote Th2 differentiation and IgE production
  • TNF-α contributes to inflammation

• Clinical manifestations range from mild to severe:

  • Allergic rhinitis (hay fever) involves sneezing, runny nose, and itchy eyes
  • Asthma involves bronchoconstriction, mucus production, and airway inflammation
  • Urticaria (hives) presents as a skin rash with raised, itchy welts
  • Anaphylaxis is a severe, life-threatening systemic reaction affecting multiple organ systems, including respiratory distress, hypotension, and shock

• Examples include:

  • Allergic asthma
  • Allergic conjunctivitis
  • Allergic rhinitis
  • Anaphylaxis due to food, insect stings, or drugs
  • Urticaria
  • Angioedema

Type II Hypersensitivity

• Known as antibody-mediated or cytotoxic hypersensitivity
• Involves IgG or IgM antibodies binding to antigens on cell or tissue surfaces
• Tissue damage mechanism:
  • Complement activation occurs when antibodies activate the complement system, leading to cell lysis or opsonization
  • Antibody-dependent cell-mediated cytotoxicity (ADCC) occurs when NK cells, macrophages, or neutrophils bind antibody-coated cells via Fc receptors, lysing the cells
  • Antibody-mediated cellular dysfunction occurs when antibodies bind to cell surface receptors, interfering with normal function
• Clinical manifestations depend on the target tissue or cells:
  • Hemolytic anemia occurs when antibodies target and destroy red blood cells
  • Thrombocytopenia occurs when antibodies target and destroy platelets
  • Goodpasture's syndrome occurs when antibodies target the glomerular basement membrane in the kidneys and the alveolar basement membrane in the lungs, leading to glomerulonephritis and pulmonary hemorrhage
  • Myasthenia gravis occurs when antibodies block acetylcholine receptors at the neuromuscular junction, leading to muscle weakness
  • Graves' disease occurs when antibodies stimulate TSH receptors on thyroid cells, leading to hyperthyroidism
• Examples include:
  • Autoimmune hemolytic anemia
  • Erythroblastosis fetalis
  • Goodpasture's syndrome
  • Myasthenia gravis
  • Graves' disease
  • Transfusion reactions

Type III Hypersensitivity

• Known as immune complex-mediated hypersensitivity
• Involves the formation of antigen-antibody complexes that deposit in tissues, leading to inflammation and tissue damage
• The mechanism includes:
  • Immune complex formation: Antibodies (usually IgG) bind to antigens, forming immune complexes
  • Deposition: Immune complexes deposit in tissues, such as blood vessel walls, kidney glomeruli, and joints
  • Complement activation: Deposited complexes activate the complement system, recruiting neutrophils and releasing inflammatory mediators
  • Tissue damage is caused by neutrophils releasing enzymes and reactive oxygen species
• Clinical manifestations depend on the site of immune complex deposition:
  • Serum sickness is a systemic reaction to foreign proteins characterized by fever, rash, joint pain, and lymphadenopathy
  • Arthus reaction is a localized reaction to an injected antigen, characterized by edema, necrosis, and inflammation
  • Systemic lupus erythematosus (SLE) is an autoimmune disease with immune complex deposition in multiple organs
  • Post-streptococcal glomerulonephritis occurs due to immune complex deposition in the kidney glomeruli following a streptococcal infection
  • Rheumatoid arthritis involves immune complex deposition in the joints
• Examples include:
  • Arthus reaction
  • Serum sickness
  • Systemic lupus erythematosus (SLE)
  • Post-streptococcal glomerulonephritis
  • Rheumatoid arthritis

Type IV Hypersensitivity

• Known as delayed-type hypersensitivity (DTH) or cell-mediated hypersensitivity
• Mediated by T cells, rather than antibodies
• The mechanism involves:
  • Sensitization: Initial antigen exposure activates and proliferates T cells
  • Activation: Subsequent exposure triggers cytokine and chemokine release by T cells, leading to inflammation and tissue damage
• Types of T cells involved:
  • Th1 cells secrete IFN-γ, activating macrophages and promoting cell-mediated immunity
  • Th2 cells secrete IL-4, IL-5, and IL-13, promoting eosinophil activation and IgE production
  • Cytotoxic T lymphocytes (CTLs) directly kill target cells expressing the antigen
• Clinical manifestations typically develop 24-72 hours after antigen exposure
• Examples include:
  • Contact dermatitis is a skin reaction to allergens such as poison ivy, nickel, or cosmetics
  • Tuberculin reaction is a localized skin reaction to tuberculin antigen, used to detect prior tuberculosis exposure
  • Granuloma formation is a chronic inflammatory response to persistent antigens, as in tuberculosis or sarcoidosis
  • Graft rejection is an immune response against transplanted organs or tissues
  • Type 1 diabetes involves T cell-mediated destruction of pancreatic beta cells
  • Multiple sclerosis involves T cell-mediated destruction of the myelin sheath in the central nervous system
• Subtypes include:
  • Contact hypersensitivity (e.g., poison ivy)
  • Tuberculin-type hypersensitivity (e.g., PPD test)
  • Granulomatous hypersensitivity (e.g., tuberculosis)

Explores Type I hypersensitivity, an immediate allergic reaction mediated by IgE antibodies. Discusses the sensitization process where IgE binds to mast cells and basophils after initial allergen exposure. Also covers activation and the variety of mediators released.