Multistep pathogenesis of autoimmune disease.
In the immune system, many tolerance checkpoints exist to prevent self-antigens from stimulating the relentless growth of self-reactive B and T lymphocytes. The genes and molecular pathways underpinning these checkpoints overlap with those involved in tumor suppression. As with an inherited predisposition to cancer, inherited defects in self-tolerance genes typically precipitate autoimmune disease stochastically after a latent phase. Multiple mutations, inherited and somatic, may be needed before a self-reactive clone bypasses sequential tolerance checkpoints resulting in the emergence of autoimmune disease.
Goodnow
Christopher C
CC
John Curtin School of Medical Research and Australian Phenomics Facility, The Australian National University, Canberra ACT 2601, Australia. chris.goodnow@anu.edu.au
D000818:Animals; D000941:Antigens / Q000276:immunology; D001327:Autoimmune Diseases / Q000473:pathology / Q000503:physiopathology*; D015551:Autoimmunity / Q000235:genetics / Q000502:physiology*; D005075:Biological Evolution; D006801:Humans; D007107:Immune System / Q000502:physiology*; D007108:Immune Tolerance / Q000235:genetics / Q000502:physiology*; D008214:Lymphocytes / Q000502:physiology; D008223:Lymphoma / Q000235:genetics / Q000276:immunology; D009154:Mutation; D015398:Signal Transduction / Q000502:physiology
D000941:Antigens