Autoimmunity and Autoimmune Diseases

Autoimmunity and Autoimmune Diseases

• Autoimmunity vs. Autoimmune Disease: Autoimmunity is the presence of self-reactive immune cells, while autoimmune diseases are clinical manifestations of autoimmunity.

Genetic and Environmental Factors in Autoimmune Diseases

• Multifactorial Nature: Most autoimmune diseases result from a complex interplay of multiple genes and environmental triggers. HLA alleles are a significant genetic factor.

• HLA-B27: A strong association exists between HLA-B27 and ankylosing spondylitis (AS). This is a key HLA association for diagnostic purposes.

Immunological Mechanisms of Autoimmune Diseases

• Immuno-privileged Sites: Certain tissues (brain, testes, fetus/placenta, eye) are considered "immuno-privileged." These sites often have mechanisms to exclude naïve lymphocytes or secrete immunosuppressive factors (e.g., TGF-β). Breakdown of immune tolerance in these sites can lead to autoimmunity.

• Molecular Mimicry: Antibodies developed against antigens from infectious agents (e.g., strep pyogenes M protein) can cross-react with self-antigens (e.g., myosin in heart valves), leading to autoimmune rheumatic heart disease.

• Types of Hypersensitivity: Autoimmune diseases can be categorized by the type of hypersensitivity reaction involved: Type II (e.g., autoimmune hemolytic anemia, autoimmune thrombocytopenia), Type III (e.g., Goodpasture's syndrome), and Type IV (e.g., potential mechanisms not explicitly listed).

Antibody-Mediated Autoimmune Diseases

• Examples of Antibody-Mediated Diseases: These diseases involve antibodies attacking self-antigens, including autoimmune hemolytic anemia (RBC surface antigens), autoimmune thrombocytopenia (platelets), Goodpasture’s syndrome (kidney and lung basement membranes), myasthenia gravis (acetylcholine receptors), Graves' disease (thyroid-stimulating hormone receptor), and systemic lupus erythematosus (diverse self-antigens, including double-stranded DNA).

Treatment of Autoimmune Diseases

• NSAIDS: Nonsteroidal anti-inflammatory drugs (e.g., aspirin, ibuprofen) can be used.

• Immunosuppressive Drugs: These drugs aim to modulate the immune response.

• Anti-inflammatory agents: Alter T-cell and neutrophil activity, lower immune cell numbers, and decrease cytokine production. Examples include corticosteroids (e.g., prednisone) and hydroxychloroquine.

• Cytokine inhibitors: Used to prevent organ transplant rejection. Cyclosporin and tacrolimus interfere with IL-2 synthesis. Rapamycin blocks the IL-2-ILR signal.

• Cytotoxic drugs: Inhibit DNA synthesis in rapidly dividing cells. Examples include azathioprine, methotrexate, and cyclophosphamide.

Immunological Tolerance

• Central Tolerance: Self-reactive T-cells and B-cells are eliminated during development in the thymus and bone marrow, respectively. Regulatory T cells are also generated in the thymus.

• Peripheral Tolerance: Mechanisms in the periphery fine-tune the immune system to avoid self-reactivity. Anergy (inactivation), T-cell suppression (by regulatory T-cells), and Fas-mediated apoptosis are examples.

• Transmissible Autoimmunity: Direct evidence includes IgG autoantibody transfer across the placenta. Indirect and circumstantial evidence includes animal models, immune cell infiltration, associations with HLA alleles, familial clustering, and response to immunosuppressive treatments.