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Tolerance?
inactivation of lymphocyte binding antigen b/c of the antigen
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How is tolerance caused?
- Centrally: inactive negative selection
- Peripherally: T/B cell negatives mature, bind MHC factor = Treg = secrete Inhibitory factors TNF-B and IL-10
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4 tolerance inhibitors:
- infection
- inflammation
- genetics
- hormones
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Molecular mimicry?
- microbes that are similar to self antigens
- Bind and activate Self-T/B cells
- Autoimmunity created
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Superantigens?
- overstimulation due to infection
- Too many activated T-cells that the Treg cells cannot inhibit
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What causes Kawasaki disease?
Superantigen
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Abnormal self-antigen presentation from infection?
- infection = inflammation
- inflammation = lymphocytes/APC cells
- APC cells present B7 to CD28 to active autoreactive Tcells
- Autoimmunity formed
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Abnormal self-antigen from non-APC cells?
- Example: B-panreatic cells
- Start to produce MHCI and MHCII
- MHC = self antigen presentation to T-cell
- Autoimmunity
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Function of Penicillin induced hemolytic anemia?
- Hapten binds to cell
- cell becomes unaffected by tolerance from Treg cells
- Activated cells become autoimmunity cells
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Sequestered antigens?
- Some lymphocytes are hidden from negative selection and tolerance mechanisms
- upon damage, these can be released and cause autoimmunity
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3 examples of sequestered antigens?
- Vasectomy: Anti-sperm
- ocular trauma: Anti-Uveitis
- CNS: Multiple Sclerosis (MS)
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Cryptic epitopes?
- Epitopes hidden from immune system
- epitopes released upon damage
- bind to antibodies and cause autoimmunity binding of other lymphocytes
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Cryptic epitope example?
- Rheumatoid factor (Rh)
- IgM binds to Fc region of epitope affecte IgG and causes phagocytosis of RBCs
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Polyclonal lymphocyte activation?
- Microbes that are non-specific
- Bind and cause B-cells to produce autoantibodies
- Attack T, B cells
- create rheumatoid factor and antinuclear antibodies
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Genetic Susceptibility: Which MHC allele is famous for self-antigen presentation?
MHCII
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function of estrogen on autoimmune diseases?
Increases chances
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Three genetic cytokines that can increase Autoimmune diseases?
- defective CTLA-4
- Fas/FasL
- IL-2/IL-2R
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