Autoimmunity

Start Studying!

Terms

undefined, object

copy deck

7 mechanisms of developing autoimmunity:: 1.Th cells and MHC
2. Special TCR
3. IFN-y
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?: -GNB
-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

-Systemic
4 types of organ-specific autoimmunity:: Hashimoto's disease
Autoimmune anemias
Goodpasture's syndrome
Insulin dependent diabetes mellitus
in Hashimoto's Thyroiditis, what are: -mediators -their effects -the result: 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, What happens?: 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 -effects -result: 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? -Mediators -Target/effect -Result: 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? -Mediator -effect -result: 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.

-Goiter
What is an example of a "Blocking Ab" autoimmune disease? -Mediator -Effect -Result: 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
-Multiple Sclerosis
-Rheumatoid arthritis
What is the main mediator of the disease, SLE (lupus)? Main effects:: -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:: -Vasculitis
-Arthritis
-Swelling

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 -effects -results: 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 -effect -result: 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

-Give corticosteroids
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.

Start Studying!

Deck Info

Number of cards 35