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  Infection & autoimmune disease   Trigger

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Triggers of Autoimmune Disease

  • Cancers: Rarely, a cancer can cause an AI disease. There are two methods:
    • Immune system tumors: Direct tumor of an immune organ such as the thymus or bone marrow (i.e. athymoma orlymphoma). However, AI disease is very rare from these disorders, so it seems that despite their importance to the immune system, a failure at these sites is not the only problem required for AI disease to result.
    • Paraneoplastic autoimmune disorders: Though very rare, there are a few types of autoimmune disease that are caused by cancers of a different part of the body. These are called "paraneoplastic" autoimmune disorders. Examples include:
      • Cancer Associated Retinopathy (CAR): An autoimmune reaction against the eye retina, caused by some types of cancers, typically lung cancer.

      The mechanism of paraneoplastic AI is believed to be that the cancer causes a hidden antigen to be shown to the immune system. This antigen is attacked, but by coincidence, this antigen is also at another body site (e.g. the retina), and the immune system mistakenly attacks the retina as an innocent bystander.

  • Radiation: UV light may damage cells and release new antigens. However, there are few examples of possible relationships between radiation and autoimmunity.
  • Immune abnormalities: Because autoimmunity is related to the immune system, various abnormalities of the immune system have been considered as possible triggers or causal factors.
    • Cancers of immune organs have been mentioned under cancers.
  • Thymus abnormalities: thymectomy: removal of the thymus. Neonatal thymectomy causes oophoritis and autoimmune gastritis in mice.
  • Chronic infections or inflammation: An infection causes heightened immune response as a natural course. It is therefore plausible that a chronic inflammation could possibly cause autoimmunity, or if not actually cause, at least provide an environment in which it would flourish.
  • Cells: One strange method of causing autoimmunity is to be injected with the cells of the body. This can sometimes upset the balance of the immune system. Some examples include:
    • Brain autoimmunity from rabies vaccinations, that were once made from brain emulsions (modern rabies vaccinations are not).
    • Encephalitis in monkey brains after injection with monkey brain cells.
  • Mitochondrial disorders: Not a general theory of AI, but a possible factor in diabetes and MS. In diabetes, mitochondrial failure might accumulate glutamate, leading to an excess of GAD and thus causing anti-GAD antibodies leading to diabetes. The genetic mitochondrial disorder Leber's Hereditary Optic Neuropathy has been associated with MS, but no clear link between mitochondria and MS has been found as yet.

Research on Triggering of Autoimmune Diseases

The methods whereby a particular trigger might cause the conversion of the immune system into an autoimmune reaction.

  • Tolerance theories: thymic deletion, clonal deletion, negative selection, apoptosis, forbidden clone, anergy, peripheral tolerance, etc. B-cells don't go to the thymus.
  • Molecular mimicry: Difficulty getting experimental confirmation in animal models. No known molecular mimics for some substances (e.g. insulin/proinsulin, but there is for islet cells and GAD).
  • Epitope crossing