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Immune Mechanisms and Autoimmunity: Understanding Tolerance and Autoimmune Diseases

Explore the breakdown of immune mechanisms that preserve tolerance to self and the development of autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosus, and spondyloarthropathies. Learn about the role of environmental and genetic factors, molecular mimicry, and the production of autoantibodies in these conditions.

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Immune Mechanisms and Autoimmunity: Understanding Tolerance and Autoimmune Diseases

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  1. Immune Mechanisms • Tolerance 3. AUTOIMMUNITY 4. Rheumatologic diseases • Rheumatoid arthritis • Systemic Lupus Erythematosis • Spondarthropathies • Inflammatory myopathies • Systemic sclerosis • Osteoarthritis

  2. Autoimmunity • Breakdown in mechanisms preserving tolerance to self • Severe enough to cause a pathological condition

  3. Autoimmune diseases • Organ specific e.g. • Insulin dependant diabetes • Myasthenia gravis • Multisystem e.g. • Rheumatoid arthritis • SLE

  4. Mechanisms ENVIRONMENTAL FACTORS • Infectious/ noninfectious triggers • Hypothesis : Molecular mimicry GENETIC FACTORS • Aberant MHC/HLA - present self peptide • Autoreactive T & B cells AUTOIMMUNE DISEASE Molecular mimicry : The antigen looks similar to a self-peptide. As a result, the body produces an immune response to the trigger factor as well as to self.

  5. Autoantibodies in Connective Tissue Diseases • Produced by B cells • May pathogenic eg. • Form immune complexes in lupus nephritis • Markers of certain diseases • Not diagnostic • Apart from rheumatic disorders, they may be found in normal population & with other conditions • Therefore only test when clinically indicated.

  6. Autoantibodies associated with disease

  7. Cellular Targets for autoantibodies Ab to intracellular proteins -proteinase 3 • cANCA Ab to cell membrane Proteins • ACLA Ab to IgG • Rheumatoid factor Antinuclear antibodies (ANA) • dsDNA • ENA – Smith, Ro , La, RNP • Centromere, topoisomerase Ribosomal & lysosomal components -t RNA synthetase • AntiJo 1 This diagram depicts the autoantibodies & their respective target antigens

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