Hypersensitivity

  1. Introduction to Hypersensitivity:

    • Hypersensitivity Reactions are immune responses that are inadequately controlled or abnormally targeted to self-tissues, leading to tissue damage.

    • These reactions can be caused by autoimmunity, reactions against microbes, or reactions against environmental antigens (e.g., allergens like pollen, dust, food, and drugs).

  2. Types of Hypersensitivity Reactions:

    • Type I (Immediate Hypersensitivity): Mediated by IgE antibodies and mast cells. It causes rapid reactions like anaphylaxis, asthma, and food allergies.

    • Type II (Antibody-Mediated Cytotoxic Hypersensitivity): Mediated by IgG or IgM antibodies that target cell surface antigens, leading to cell destruction (e.g., autoimmune hemolytic anemia, Goodpasture syndrome).

    • Type III (Immune Complex-Mediated Hypersensitivity): Caused by the deposition of antigen-antibody complexes in tissues, leading to inflammation and tissue damage (e.g., systemic lupus erythematosus, post-streptococcal glomerulonephritis).

    • Type IV (Cell-Mediated Hypersensitivity): Mediated by T cells (CD4+ and CD8+), causing delayed reactions like contact dermatitis, tuberculosis, and type 1 diabetes.

  3. Type I Hypersensitivity (Immediate Hypersensitivity):

    • Mechanism:

      • Sensitization Phase: Allergen exposure leads to IgE production, which binds to mast cells.

      • Re-exposure Phase: Allergen binds to IgE on mast cells, causing degranulation and release of mediators like histamine, leukotrienes, and prostaglandins.

    • Clinical Examples:

      • Systemic Reactions: Anaphylaxis (e.g., penicillin allergy).

      • Local Reactions: Asthma, hay fever, food allergies, atopic dermatitis.

  4. Type II Hypersensitivity (Antibody-Mediated Cytotoxic Hypersensitivity):

    • Mechanism:

      • Opsonization and Phagocytosis: Antibodies coat cells, leading to phagocytosis (e.g., transfusion reactions).

      • Complement Activation: Antibodies activate complement, causing inflammation and cell lysis (e.g., acute rheumatic fever).

      • Antibody-Mediated Cellular Dysfunction: Antibodies block or stimulate cell surface receptors (e.g., myasthenia gravis, Graves disease).

    • Clinical Examples: Autoimmune hemolytic anemia, Goodpasture syndrome, myasthenia gravis, Graves disease.

  5. Type III Hypersensitivity (Immune Complex-Mediated Hypersensitivity):

    • Mechanism:

      • Immune Complex Formation: Antigen-antibody complexes deposit in tissues, activating complement and recruiting neutrophils, leading to inflammation and tissue damage.

    • Clinical Examples:

      • Systemic Lupus Erythematosus (SLE): Immune complexes deposit in kidneys, joints, and blood vessels.

      • Post-Streptococcal Glomerulonephritis: Immune complexes deposit in kidney glomeruli after streptococcal infection.

      • Serum Sickness: Immune reaction to foreign proteins in serum.

  6. Type IV Hypersensitivity (Cell-Mediated Hypersensitivity):

    • Mechanism:

      • Delayed-Type Hypersensitivity (DTH): CD4+ T cells secrete cytokines, recruiting macrophages and causing inflammation (e.g., tuberculosis, contact dermatitis).

      • Cytotoxic T Cell-Mediated Reaction: CD8+ T cells directly kill target cells (e.g., type 1 diabetes, viral infections).

    • Clinical Examples: Contact dermatitis, tuberculosis, type 1 diabetes, multiple sclerosis.