Type I Hypersensitivity

• Hypersensitivity is classified into four types: Type I, Type II, Type III, and Type IV (delayed reactions).

Type I Hypersensitivity

• Also known as immediate hypersensitivity.
• Reactions may involve the skin, eyes, nasopharynx, bronchopulmonary tissues, and gastrointestinal tract.
• Allergens include inhalants like pollen and fungal allergens, injectants like drugs, and contact allergens like antiseptic spray.
• The mechanism involves IgE production in response to specific antigens (allergens).
• IgE has a high affinity for receptors on mast cells and basophils.
• Subsequent exposure to the same allergen cross-links cell-bound IgE, triggering the release of active substances.
• Cross-linking of IgE Fc-receptor is important in mast cell triggering.
• Mast cell degranulation is preceded by increased Ca++ influx.

Mediators of Immediate Hypersensitivity:

• Preformed mediators in granules include histamine, tryptase, and ECF-A.
  • Histamine causes bronchoconstriction, mucus secretion, vasodilation, and vascular permeability.
  • Tryptase is responsible for proteolysis.
  • ECF-A attracts eosinophils and neutrophils.
• Newly formed mediators include leukotriene B4, leukotriene C4, D4, and prostaglandins D2.
  • Leukotriene B4 is a basophil chemoattractant.
  • Leukotriene C4 and D4 are similar to histamine, but 1000x more potent.
  • Prostaglandins D2 cause edema and pain.

Diagnostic tests for immediate hypersensitivity include:

• Skin (prick and intradermal) tests.
• Measurement of total IgE and specific IgE antibodies using ELISA.

Treatment includes:

• Avoidance of exposure.
  • Cover mattresses and pillows with dust mite-resistant covers for dust mite allergens.
  • Remove indoor plants and dry/remove wet carpets for fungal allergens.
• Symptomatic treatment.
  • Antihistamines block histamine receptors.
  • Chromolyn sodium inhibits mast cell degranulation by inhibiting Ca++ influx.
  • Leukotriene receptor blockers or cyclooxygenase inhibitors treat late-onset allergic symptoms mediated by leukotrienes.
  • Bronchodilators (inhalants) provide short-term relief from bronchoconstriction.
• Immunotherapy (administration of gradually increasing allergen extract doses).
  • Aims to teach the immune system to tolerate the allergen.
  • This stops IgE production and increases allergen-specific IgG4 antibodies.
  • Blocking activity through the inhibition of allergen-induced, IgE-mediated release of inflammatory mediators from mast cells.

Type II Hypersensitivity

• Also known as cytotoxic hypersensitivity and can affect a variety of organs and tissues.
• Antigens are typically endogenous, but exogenous chemicals (haptens) can lead to this type of hypersensitivity.
• Primarily mediated by IgM or IgG classes.
  • Mechanisms include complement-mediated lysis.
  • Phagocytes and killer cells may play a role (ADCC).

Types of Type II Hypersensitivity

• RBCs lysis:
  • Incompatible blood transfusion:
    • ABO: Intravascular hemolysis with nausea, fever, rigors, and back pain.
    • RH: Extravascular hemolysis via phagocytic cells.
  • Erythroblastosis fetalis:
    • Mother (Rh negative) gives birth to Rh positive infant, fetal blood enters maternal circulation producing antibody against Rh antigen.
    • In subsequent pregnancies, the antibody crosses the placenta and attaches to Rh antigen on fetal RBCs.
    • Extravascular hemolysis leads to anemia, jaundice, hepatosplenomegaly, and bilirubin encephalopathy.
  • Autoimmune hemolytic disease.
• WBCs lysis:
  • Granulocytopenia.
  • Systemic lupus erythematosus (SLE).
• Platelet destruction.
• Antigens are also called agglutinogens.
• Antibodies are called agglutinins.

Type III Hypersensitivity

• (Immune complex hypersensitivity).
• Mediated by soluble immune complexes, mostly of IgG, though IgM may be involved.
• Antigens may be exogenous or endogenous.
  • Exogenous antigens: Chronic bacterial, viral, or parasitic infections.
  • Endogenous antigens: Non-organ-specific autoimmunity (SLE).

Mechanism

• The antigen is soluble and not attached to the organ involved.
• Soluble Ag-antibody complexes penetrate the endothelium of blood vessels and deposit on the vascular basement membrane.
• This stimulates complement and chemotactic factors like C5a, which attract neutrophils.
• Neutrophils infiltrate the area and release lysosomal enzymes, leading to destruction of the basement membrane.

Types of Type III Hypersensitivity

• Arthus reaction.
• Serum sickness.
• Hypersensitivity pneumonitis.
• Posstreptococcal glomerulonephritis.
• Autoimmune disease: Rheumatoid Arthritis (RA), SLE.

Type IV Hypersensitivity

• Also known as cell-mediated, or delayed-type hypersensitivity.
• A classical example is the tuberculin (Montoux) reaction that peaks 48 hours after antigen injection (PPD or old tuberculin).
• Lesion is characterized by induration and erythema.

Mechanism:

• CD4+ helper T cells recognize antigen in a complex with Class II MHC.
• Antigen-presenting cells (macrophages) secrete IL-12, stimulating CD4+ Th1 cell proliferation.
• CD4+ T cells secrete IL-2 and interferon-gamma, further inducing the release of other Th1 cytokines.
• Activated CD8+ T cells destroy target cells on contact.
• Chemokines like IL-8 and monocyte chemotactic and activating factor (MCAF) lead to macrophage activation.
• This results in the production of hydrolytic enzymes, leading to a maximal local tissue reaction in 48-72 hours.