Card Set Information
autoimmunity immune immunity bod pathology
4 common targets for organ-specific autoimmunity (with examples)
: Grave's disease, Hashimoto's thryroiditis
: pernicious anaemia
what makes the common targets for organ-specific autoimmunity common? (2)
make organ specific proteins
3 non-organ specific targets for autoimmunity (with examples)
: SLE (systemic lupus erythematosis)
3 general mechanisms of autoimmune pathology
Autoantibodies: 5 examples
Her Royal Majesty GG
: to TSH receptor: hyperthryoidism (bulging eyes, nervousness, heat intolerance
: to ACh receptor: downregulation of AchR: muscle weakness
: to Rh blood group antigens: RBC destruction
: to collagen type IV: glomerulonephritis
Explain the problem with 'immune complex mediated' autoimmunity
Deposition in tissues
Depletion of complement
How are immune complexes normally removed?
Complement binds antigen. IgM binds to C3bR on RBCs. Transport to liver and spleen for destruction by macrophages.
2 examples of immune complex mediated autoimmunity
: 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.
: Subacute bacterial endocarditis: to bacterial antigens: endocarditis, glomerulonephritis
4 mechanisms of damage with T cell mediated autoimmunity
CTL mediated destruction
TNF-alpha mediated destruction
Induction of apoptosis by Fas ligand
3 examples of T cell mediated autoimmunity
: to synovial joint antigens: joint inflammation and destruction
: to myelin basic protein proteolipoprotein: brain degeneration, paralysis
: to pancreatic beta cells
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.
Most important genetic risk factor for autoimmune disease
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)
example of amino acid chain conferring susceptibility to an autoimmune disease
Position 57 in HLA-DQbeta
asp is protective (charged, forms electrostatic attractions)
ser/ala/val is susceptible (hydrophobic)
affects binding of diabetogenic peptides?
2 factors other than genetic which can alter susceptibility to autoimmune disease (with examples)
percentage contributions to susceptibility to T1D
25%? other genes?
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
: pathogen epitope similar to self epitope
: activates pAPCs: may activate anergic autoreactive T cells
: neoantigen eg pathogen binding to self
2 types of animal models of autoimmunity
: genetic inbreeding eg Ob mouse
: eg injecting with MBP and CFA to produce EAE (Experimental autoimmune encephalmyelitis)
3 drug types for autoimmune diseases
: thryoxine for Grave's disease
: cyclosporin, rapamycin, steroids
Role of Th17 cells
Produce IL17. Recruit neutrophils to sites of infection.
Role of Tfh cells
Activate B cells in B cell follicles.