Glossary of Autoimmunity
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- 7 mechanisms of developing autoimmunity:
- 1.Th cells and MHC
2. Special TCR
4. Sequestered Antigen Release
5. Molecular Mimicry by Pathogens
6. Inappropriate Class 2 MHC expression
7. Polyclonal B-cell activation
- What is requisite of Th cells and MHC in order for there to be an autoimmune response?
- Both the TcR and MHC are capable of binding SELF proteins.
The APC chew up SELF, presents it to Thelper.
- What makes the TCR special in an autoimmune response?
- It recognized a SELF antigen; the only way it can do so is by BYPASSING negative selection in the thymus.
- What does negative selection in the thymus do to TCR?
- Selects Tcells that bind self-ag with self-MHC too strongly.
Makes them die by apoptosis.
This is failed in autoimmunity.
- What are "Special" TcRs?
- Tcell receptors that underwent normal random gene rearrangement; it turned out to be reactive to self antigen. After release into circulation, binds its antigen.
- How does IFN-y contribute to autoimmunity?
- IFN-y promotes the production/secretion of other cytokines that upregulate MHC1/2.
In Autoimmunity, this occurs on non-APC cells; they should not be presenting Ag.
- How does inappropriate expression of MHC2 contribute to autoimmunity?
- If non-APCs have MHC2, they can present self-antigens that otherwise would not be presented to Tcells.
Presentation sensitizes a Tcell population and results in self-reaction.
- Why is improper activation of Th cells bad?
- -They are the central secretors of cytokines that turn on the whole immune response.
- What is an example of cells that have inappropriate MHC2 expression?
- Beta-cells in the pancreas.
- How does sequestered Ag release cause autoimmunity?
- During T-cell matuation, the naieve cells are not exposed to sperm/brain cells.
If injury/surgery allows release of the sequestered antigens, they'll be seen as non-self.
- How does molecular mimicry by pathogens cause autoimmunity?
- Some bacteria resemble brain or cardiac cells.
Their epitope size/chemical structure resembles self-proteins.
This causes cross-linking and sensitizing of Tcells.
- Why is polyclonal Bcell activation bad?
- Polyclonal activation of Bcells is nonspecific and unregulated; the Bcells will express mainly IgM, and some can bind self proteins.
- How does polyclonal Bcell activation cause autoimmunity?
- DUring the activation/proliferation, some Bcells are activated that bind self-Ag.
- What causes polyclonal Bcell activation in humans?
-Epstein-barr virus for mono
-SLE - lupus
- What is Autoimmunity CAUSED BY?
- the activation of self-reactive T and B cells.
- What are the two types of autoimmunity?
- -Organ specific
- 4 types of organ-specific autoimmunity:
- Hashimoto's disease
Insulin dependent diabetes mellitus
- in Hashimoto's Thyroiditis, what are:
- Th cells and antibody sensitized to thyroid-produced proteins.
Effect: DTH, inflammatory response, germinal centers, granulomas.
Result: Hyperthyroidism - not enough proteins put out
- 2 types of autoimmune anemias,
- Pernicious - Ab to intrinsic factor forms; can't take up Vitamin B12
Hemolytic - Ab forms to RBC surface antigens; activates complement and causes RBC lysis.
- What happens in Goodpasture's Syndrome
- Mediators: antibody to basement membrane cells in kidney and lung
Effect: activate complement, inflammatory response.
Result: renal failure and hemorrhage in lungs.
- What happens in IDDM?
- Antibodies form to Beta-cells of the pancreas - these cells produce insulin.
-Cytokine TH1 subset release; DTH, inflammation, complement, ADCC - everything.
-Result: low insulin production, high blood glucose levels, pancreas damage.
- 2 contrasting ways of causing autoimmunity with antibody:
- -Activating antibody (activates a certain molecule or tissue)
-Blocking (prevents a certain function).
- What is an example of an "Activating Ab" autoimmune disease?
- Grave's disease
-An antibody that mimics TSH is produced.
-Ab binds TSH receptor on thyroid; this Ab is not regulated like normal TSH; causes overproduction of Thyroid hormones.
- What is an example of a "Blocking Ab" autoimmune disease?
- Myasthenia Gravis
-Antibodies to acetylcholine receptors.
-Bind in place of real acetylcholine; block the activation for muscle movement.
-Can result in muscle atrophy, loss of even autonomic muscular functions -breathing.
- What is Systemic Autoimmunity?
- A general lack of immune regulation
-Hyperactive T and B cells.
- 3 examples of Systemic autoimmune disorders:
- -Systemic Lupus Erythematosus
- What is the main mediator of the disease, SLE (lupus)?
- -A general production of auto-antibodies to a vast array of tissue antigens, including RBCs and DNA.
Ag-Ab complexes are depositied in tissue and cause Serum Sickness - Type 3 hypersensitivity.
- Main symptoms of Lupus:
Complement-mediated effects - inflammation and lysis of self sells
- What is vasculitis?
- occlusions in small blood vessels - result of neutrophils attaching to them in lupus.
- Multiple Sclerosis
- Mediators: Tcells reactive to myelin sheaths around nervous tissue in CNS.
Effects: lesions on the CNS tissue
Results: neurologic dysfunction.
- What is Rheumatoid arthritis?
- mediators: auto antibodies to Ig-G
effect: form complexes with Ig-M, deposited in joints.
Result: chronic inflammation of joints. Pain.
- 2 very General treatment strategies for autoimmunity:
- -Remove the thymus
- What is Plasmapheresis?
- Taking plasma out of patients with lupus, centrifugin, and returning only the blood cells.
The Ag-ab complexes causing serum sickness are removed with the plasma and lessen the disease symptoms.
- What are 2 more-specific treatment options for autoimmune disease?
- -Cyclosporin -> blocks signal transduction mediated by the Tcell receptor, prevents proliferation of only ACTIVATED cells.
-Monoclonal Ab (humanized) to the alpha subunit of high-affinity IL-2R; prevents proliferation/activation of the sensitized Tcells that have constitutive high-levels.
- How can Tolerance aid in preventing autoimmunity?
- Oral eating of antigen induces tolerance, immunologic unresponsiveness.
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