Autoimmune diseases

  1. Introduction to Autoimmune Diseases:

    • Autoimmune Diseases occur when the immune system mistakenly attacks the body's own tissues due to a breakdown in self-tolerance.

    • This leads to the formation of autoantibodies and immune reactions against self-antigens.

    • Autoimmune diseases can be organ-specific (targeting a single organ) or systemic (affecting multiple organs).

  2. Self-Tolerance and Its Breakdown:

    • Self-Tolerance: The immune system's ability to recognize and not attack the body's own tissues.

      • Central Tolerance: Occurs in the thymus (for T cells) and bone marrow (for B cells), where self-reactive lymphocytes are deleted during maturation.

      • Peripheral Tolerance: Occurs in peripheral tissues and involves mechanisms like anergy (functional inactivation), deletion (apoptosis), and suppression by regulatory T cells (Tregs).

    • Breakdown of Self-Tolerance: Leads to autoimmune diseases. Mechanisms include:

      • Molecular Mimicry: Microorganisms with antigens similar to self-antigens trigger cross-reactive immune responses (e.g., rheumatic fever after streptococcal infection).

      • Polyclonal Lymphocyte Activation: Non-specific activation of lymphocytes by viruses or bacterial endotoxins.

      • Release of Sequestered Antigens: Hidden antigens (e.g., in the eye or testes) are exposed to the immune system, triggering an autoimmune response.

      • Failure of Apoptosis or Suppression: Self-reactive lymphocytes escape deletion or suppression.

  3. Mechanisms of Autoimmune Disease Development:

    • Type II Hypersensitivity: Autoantibodies bind to cell surface antigens, leading to cell destruction (e.g., Hashimoto's thyroiditis).

    • Type III Hypersensitivity: Immune complexes deposit in tissues, causing inflammation and damage (e.g., systemic lupus erythematosus, SLE).

    • Genetic Factors: Autoimmune diseases often run in families and are linked to HLA genes (especially HLA-DR and HLA-DQ).

    • Role of Microorganisms: Infections can trigger autoimmunity through molecular mimicry, breakdown of T-cell anergy, or release of sequestered antigens.

  4. Examples of Autoimmune Diseases:

    • Organ-Specific Autoimmune Diseases:

      • Hashimoto's Thyroiditis: Autoantibodies target thyroid antigens (thyroglobulin, thyroid peroxidase), leading to hypothyroidism.

      • Type 1 Diabetes Mellitus: Autoimmune destruction of pancreatic beta cells, leading to insulin deficiency.

    • Systemic Autoimmune Diseases:

      • Systemic Lupus Erythematosus (SLE): A multisystem disease with autoantibodies against nuclear antigens (e.g., DNA, histones), causing widespread tissue damage.

      • Rheumatoid Arthritis: Autoimmune attack on joints, leading to inflammation and joint destruction.

  5. Pathogenesis of Autoimmune Diseases:

    • Tissue Damage: Caused by autoantibodies and immune complexes, leading to inflammation and organ dysfunction.

    • Clinical Features: Vary depending on the disease but often include inflammation, tissue damage, and organ dysfunction.

    • Hypersensitivity Reactions: Type II (cell surface antigens) and Type III (immune complexes) are common mechanisms.

  6. Genetic and Environmental Factors:

    • Genetic Predisposition: HLA genes play a significant role in susceptibility to autoimmune diseases.

    • Environmental Triggers: Infections, trauma, and exposure to certain chemicals can trigger autoimmune responses.