Hypersensitivity reactions occur when our immune system overreacts to harmless substances. These reactions can range from mild allergies to life-threatening anaphylaxis, involving complex interactions between allergens, antibodies, and immune cells.

There are four main types of hypersensitivity reactions, each with unique mechanisms and symptoms. Understanding these types helps diagnose and treat allergies, autoimmune disorders, and other immune-mediated conditions effectively.

Types and Mechanisms of Hypersensitivity Reactions

Introduction to Hypersensitivity

Hypersensitivity reactions occur when the immune system responds excessively or inappropriately to an antigen, leading to tissue damage and disease. These reactions involve complex interactions between allergens, antibodies, and various immune cells, often resulting in inflammation and other harmful effects.

Types of hypersensitivity reactions

• Type I (Immediate) Hypersensitivity
  • Mediated by IgE antibodies bound to mast cells and basophils
  • Allergen cross-links IgE triggering degranulation and release of histamine, leukotrienes, and other inflammatory mediators
  • Causes vasodilation, smooth muscle contraction, and increased mucus secretion leading to symptoms (anaphylaxis, allergic rhinitis, asthma)
  • Involves a sensitization phase where initial exposure to an allergen leads to IgE production
• Type II (Antibody-Mediated) Hypersensitivity
  • Mediated by IgG and IgM antibodies binding to cell surface antigens
  • Leads to cell destruction through complement activation and antibody-dependent cell-mediated cytotoxicity (ADCC)
  • Results in cell lysis, inflammation, and tissue damage (autoimmune hemolytic anemia, Goodpasture syndrome)
• Type III (Immune Complex-Mediated) Hypersensitivity
  • Antigen-antibody complexes deposit in tissues activating complement and recruiting immune cells
  • Causes inflammation and tissue damage (serum sickness, systemic lupus erythematosus)
• Type IV (Delayed-Type) Hypersensitivity
  • Cell-mediated immune response involving activated T cells releasing cytokines
  • Triggers inflammation and tissue damage with delayed onset of 24-72 hours after exposure
  • Occurs in contact dermatitis and positive tuberculosis skin tests

Blood type incompatibility issues

• ABO Blood Types
  • Four main types determined by presence or absence of A and B antigens on red blood cells: A, B, AB, and O
  • Natural antibodies form against missing antigens (anti-A in type B individuals, anti-B in type A)
  • Transfusion of mismatched blood leads to recipient antibodies attacking donor red blood cells causing agglutination and hemolysis
• Rh Factor
  • Rh(D) antigen either present (Rh+) or absent (Rh-) on red blood cells
  • Rh- individuals can develop anti-Rh antibodies if exposed to Rh+ blood
  • Subsequent Rh+ exposure triggers rapid antibody response and destruction of Rh+ red blood cells
• Hemolytic Disease of the Newborn (HDN)
  • Occurs when Rh- mother carries Rh+ fetus and develops anti-Rh antibodies
  • Maternal anti-Rh antibodies cross placenta and attack fetal red blood cells
  • Leads to fetal anemia, jaundice, and potentially hydrops fetalis
  • Prevented by administering Rh immunoglobulin (RhoGAM) to Rh- mothers

Diagnosis and treatment of hypersensitivities

• Type I Hypersensitivity
  • Diagnosis: skin prick tests for allergens, measuring serum IgE levels, basophil activation tests
  • Treatment: allergen avoidance, antihistamines to block effects, epinephrine for anaphylaxis
• Type II Hypersensitivity
  • Diagnosis: direct and indirect Coombs tests for antibodies, tissue biopsy
  • Treatment: corticosteroids and immunosuppressants to reduce inflammation, plasmapheresis to remove antibodies
• Type III Hypersensitivity
  • Diagnosis: measuring serum complement levels, tissue biopsy, immunofluorescence staining
  • Treatment: corticosteroids and immunosuppressants to limit inflammation, plasmapheresis to clear immune complexes
• Type IV Hypersensitivity
  • Diagnosis: patch tests with triggering agents, lymphocyte transformation tests
  • Treatment: avoiding triggers, topical or systemic corticosteroids to reduce inflammation

Immune Tolerance and Hypersensitivity

• Immune tolerance is the process by which the immune system learns to distinguish between self and non-self antigens
• Breakdown of tolerance can lead to hypersensitivity reactions and autoimmune diseases
• Mechanisms of tolerance include:
  • Central tolerance: elimination of self-reactive T and B cells during development
  • Peripheral tolerance: suppression of mature self-reactive lymphocytes in tissues
• Factors influencing tolerance and hypersensitivity:
  • Genetic predisposition
  • Environmental exposures to allergens and other antigens
  • Regulatory T cells that help maintain tolerance