26- Autoimmunity

• Systemic lupus erythematosus

  Autoimmune disease where nucleic acids are wrapped in self-proteins, and when they break open and get outside in high quantities they are DAMPS, leading to immune complexes, complement activation, and autoreactivity
• Goodpasture's Syndrome


  Autoimmune disease where antibodies target collagen in basement membrane, affecting glomerulus, alveoli, and inner ear. Alveoli only affected in smokers as they destroy the epithelial layer, exposing the basement membrane.
• Autoimmunity is inheritable and mostly associated with MHC II: DR4 and rheumatoid arthritis. Can also have non-MHC involved: TCR, cytokines.
• Autoimmunity is very dependent on hormones. Women have stronger, bigger, better immune responses (especially when pregnant), making them more likely to have autoimmune antibodies.
• Environment can also play a role in autoimmunity.
• Immunosuppressant Drugs


  Corticosteroids, cyclophosphamide. Con: patient left vulnerable to disease. Deplete specific cell subsets.
• 4 types of Hypersensitivity

  • Allergy and Atopy (IgE mediated)
  • Antibody Mediated (IgG or IgM mediated)
  • Immune Complex-Mediated (Immune complexes mediated)
  • Delayed Type (T cell mediated)
• Autoimmunity

  A specific adaptive immune response mounted against self-antigens. Problem is that it is impossible for immune responses to completely remove the antigen, so the response can never really end, causing sustained inflammatory injury.
• Autoimmunity can be a failure of tolerance: unable to select against self-reacting cells. Tregs develop in gut to stop immune response to harmless pathogens.
• Autoimmunity comes as a natural consequence of random B and T cell receptor development. Elimination of self-reactors is not perfect and some normal receptors still will react with low affinity to self.
• Genetic and environmental factors are involved in autoimmunity, including MHC genotype and prior response to pathogens that have epitopes similar to self.
• Effector Mechanisms in autoimmunity often involve auto-antibodies, where antibody-antigen complexes induce phagocytosis and complement activation. Antibodies can also block receptor functions.