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