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Updated: Jul 24 2019



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  • Snapshot
    • A 46-year-old woman presents to her primary care physician with double vision and weakness. She reports her double vision occurs when watching television or reading a book, and her weakness is most severe at the end of the day. On physical exam, when asking the patient to look up for a few minutes, ptosis ensues. When applying a glove filled with ice on the ptosis, it improves. Laboratory testing is significant for autoantibodies directed against acetylcholine receptors. (Myasthenia gravis)
  • Introduction
    • Clinical definition
      • an adaptive immune response directed against self-antigens resulting in
        • autoimmune disease
    • Background
      • lymphocyte development in the central lymphoid organ is accompanied by
        • gene rearrangements that inevitably produce
          • lymphocytes that react to self-antigens
            • these lymphocytes are normally removed through a number of mechanisms (e.g., negative selection), and this is termed self-tolerance
              • autoimmunity results from an impairment in self-tolerance
    • Pathogenesis
      • an immune response is triggered by self-antigens (also called autoantigens)
        • which results in the production of
          • autoreactive effector cells and autoantibodies leading to
            • tissue damage and thus autoimmune disease
      • autoimmunity may be triggered by
        • failure of self-tolerance mechanisms and environmental causes (e.g., infection) in
          • genetically predisposed people
      • molecular mimicry
        • a phenomenon where antigens resemble molecules in the host
        • this results in the production of antigen-directed antibodies that
          • cross-react with the self-molecule
        • note that effector cells may be autoreactive as well if the processed pathogen peptide is similar to the host's peptides
        • one example is rheumatic fever, which results from
          • antibodies being directed against the M protein of S. pyogenes which
            • cross-react with self-molecules (e.g., in the heart valves)
  • Clinical Correlate
      • Select Autoimmune Diseases
      • Disease
      • Pathogenesis
      • Findings
      • Rheumatoid arthritis
      • Autoreactive T-cells act on antigens found in the synovium of the joint
      • Inflammatory arthritis
      • Graves' disease
      • Autoantibodies act on the thyroid stimulating hormone (TSH) receptor
      • Hyperthyroidism
      • Systemic lupus erythematosus
      • Autoantibodies and autoreactive T-cells act on
        • DNA
        • chromatin proteins
        • ribonucleoproteins
      • Vasculitis
      • Rash
      • Glomerulonephritis
      • Multiple sclerosis
      • Autoreactive T-cells act on
        • central nervous system antigens
      • Myelin sheath destruction and sclerotic plaque formation
      • Myasthenia gravis
      • Autoantibodies act on
        • acetylcholine receptors
        • muscle-specific tyrosine kinase
      • Fatiguable muscles weakness
      • Type 1 diabetes mellitus
      • Autoreactive T-cells act on antigens found on
        • pancreatic islet cells
      • ↓ Insulin production
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