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  1. 4 common targets for organ-specific autoimmunity (with examples)
    • thyroid: Grave's disease, Hashimoto's thryroiditis
    • adrenals
    • stomach: pernicious anaemia
    • pancrease: T1D
  2. what makes the common targets for organ-specific autoimmunity common? (2)
    • well vascularised
    • make organ specific proteins
  3. 3 non-organ specific targets for autoimmunity (with examples)
    • skin: scleroderma
    • kidney: SLE (systemic lupus erythematosis)
    • joints: RA
  4. 3 general mechanisms of autoimmune pathology
    • antibody
    • immune complex
    • t cell
  5. Autoantibodies: 5 examples
    • Her Royal Majesty GG
    • Grave's disease: to TSH receptor: hyperthryoidism (bulging eyes, nervousness, heat intolerance
    • Myasthenia Gravis: to ACh receptor: downregulation of AchR: muscle weakness
    • Rheumatic fever:
    • Haemolytic anaemia: to Rh blood group antigens: RBC destruction
    • Goodpasture's syndrome: to collagen type IV: glomerulonephritis
  6. Explain the problem with 'immune complex mediated' autoimmunity
    • Deposition in tissues
    • Depletion of complement
  7. How are immune complexes normally removed?
    Complement binds antigen. IgM binds to C3bR on RBCs. Transport to liver and spleen for destruction by macrophages.
  8. 2 examples of immune complex mediated autoimmunity
    • SLE: Systemic lupus erythematosus: anti-cytoplasmic and anti-nuclear antibodies: complement depletion. Butterfly rash on face, glomerulonephritis, vasculitis, arthritis. Complement deficiencies that impair immune clearance (Eg C1, C2, C4) are predisposing.
    • SBE: Subacute bacterial endocarditis: to bacterial antigens: endocarditis, glomerulonephritis
  9. 4 mechanisms of damage with T cell mediated autoimmunity
    • CTL mediated destruction
    • Macrophage activation
    • TNF-alpha mediated destruction
    • Induction of apoptosis by Fas ligand
  10. 3 examples of T cell mediated autoimmunity
    • Mr T
    • RA: to synovial joint antigens: joint inflammation and destruction
    • MS: to myelin basic protein proteolipoprotein: brain degeneration, paralysis
    • T1D: to pancreatic beta cells
  11. Exp for T cell mediated autoimmunity
    • Infect mouse with MBP and CFA. It gets EAE (experimental autoimmune encephalomyelitis). Isolate T cells with receptors specific for MBP. Inject these into a healthy mouse. They all get EAE, most die.
    • Because the T cells attack self MBP.
  12. Most important genetic risk factor for autoimmune disease
  13. 2 examples of HLA allotypes associated with autoimmune diseases...
    • HLA-27 for ankylodising spondylosis (90x) and Goodpasture's syndrome (10x)
    • HLA-DR2 for Goodpasture's (16x)
  14. example of amino acid chain conferring susceptibility to an autoimmune disease
    • T1D
    • Position 57 in HLA-DQbeta
    • asp is protective (charged, forms electrostatic attractions)
    • ser/ala/val is susceptible (hydrophobic)
    • affects binding of diabetogenic peptides?
  15. 2 factors other than genetic which can alter susceptibility to autoimmune disease (with examples)
  16. percentage contributions to susceptibility to T1D
    • 50% environment
    • 25% HLA
    • 25%? other genes?
  17. 2 triggers of autoimmunity
    • Release of sequestered antigen: eg autoimmune sympathetic opthalmia - damage to one eye leads to attack of the other
    • T cell tolerance bypass: in 3 ways
    • Molecular mimickry: pathogen epitope similar to self epitope
    • Inflammation: activates pAPCs: may activate anergic autoreactive T cells
    • Modification: neoantigen eg pathogen binding to self
  18. 2 types of animal models of autoimmunity
    • Spontaneous: genetic inbreeding eg Ob mouse
    • Induced: eg injecting with MBP and CFA to produce EAE (Experimental autoimmune encephalmyelitis)
  19. 3 drug types for autoimmune diseases
    • organ specific: thryoxine for Grave's disease
    • immunosuppressive (blunt!): cyclosporin, rapamycin, steroids
    • anti-TNF etc
  20. Role of Th17 cells
    Produce IL17. Recruit neutrophils to sites of infection.
  21. Role of Tfh cells
    Activate B cells in B cell follicles.
Card Set:
2012-12-15 09:39:50
autoimmunity immune immunity bod pathology

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