Autoimmunity

Front 1

7 mechanisms of developing autoimmunity:

Back 1

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

Front 2

What is requisite of Th cells and MHC in order for there to be an autoimmune response?

Back 2

Both the TcR and MHC are capable of binding SELF proteins.

The APC chew up SELF, presents it to Thelper.

Front 3

What makes the TCR special in an autoimmune response?

Back 3

It recognized a SELF antigen; the only way it can do so is by BYPASSING negative selection in the thymus.

Front 4

What does negative selection in the thymus do to TCR?

Back 4

Selects Tcells that bind self-ag with self-MHC too strongly.

Makes them die by apoptosis.

This is failed in autoimmunity.

Front 5

What are "Special" TcRs?

Back 5

Tcell receptors that underwent normal random gene rearrangement; it turned out to be reactive to self antigen. After release into circulation, binds its antigen.

Front 6

How does IFN-y contribute to autoimmunity?

Back 6

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.

Front 7

How does inappropriate expression of MHC2 contribute to autoimmunity?

Back 7

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.

Front 8

Why is improper activation of Th cells bad?

Back 8

-They are the central secretors of cytokines that turn on the whole immune response.

Front 9

What is an example of cells that have inappropriate MHC2 expression?

Back 9

Beta-cells in the pancreas.

Front 10

How does sequestered Ag release cause autoimmunity?

Back 10

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.

Front 11

How does molecular mimicry by pathogens cause autoimmunity?

Back 11

Some bacteria resemble brain or cardiac cells.
Their epitope size/chemical structure resembles self-proteins.
This causes cross-linking and sensitizing of Tcells.

Front 12

Why is polyclonal Bcell activation bad?

Back 12

Polyclonal activation of Bcells is nonspecific and unregulated; the Bcells will express mainly IgM, and some can bind self proteins.

Front 13

How does polyclonal Bcell activation cause autoimmunity?

Back 13

DUring the activation/proliferation, some Bcells are activated that bind self-Ag.

Front 14

What causes polyclonal Bcell activation in humans?

Back 14

-GNB
-Epstein-barr virus for mono
-SLE - lupus

Front 15

What is Autoimmunity CAUSED BY?

Back 15

the activation of self-reactive T and B cells.

Front 16

What are the two types of autoimmunity?

Back 16

-Organ specific

-Systemic

Front 17

4 types of organ-specific autoimmunity:

Back 17

Hashimoto's disease
Autoimmune anemias
Goodpasture's syndrome
Insulin dependent diabetes mellitus

Front 18

in Hashimoto's Thyroiditis, what are:
-mediators
-their effects
-the result

Back 18

Th cells and antibody sensitized to thyroid-produced proteins.

Effect: DTH, inflammatory response, germinal centers, granulomas.

Result: Hyperthyroidism - not enough proteins put out

Front 19

2 types of autoimmune anemias,


What happens?

Back 19

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.

Front 20

What happens in Goodpasture's Syndrome
-mediators
-effects
-result

Back 20

Mediators: antibody to basement membrane cells in kidney and lung

Effect: activate complement, inflammatory response.

Result: renal failure and hemorrhage in lungs.

Front 21

What happens in IDDM?
-Mediators
-Target/effect
-Result

Back 21

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.

Front 22

2 contrasting ways of causing autoimmunity with antibody:

Back 22

-Activating antibody (activates a certain molecule or tissue)

-Blocking (prevents a certain function).

Front 23

What is an example of an "Activating Ab" autoimmune disease?

-Mediator
-effect
-result

Back 23

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

Front 24

What is an example of a "Blocking Ab" autoimmune disease?

-Mediator
-Effect
-Result

Back 24

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.

Front 25

What is Systemic Autoimmunity?

Back 25

A general lack of immune regulation

-Hyperactive T and B cells.

Front 26

3 examples of Systemic autoimmune disorders:

Back 26

-Systemic Lupus Erythematosus
-Multiple Sclerosis
-Rheumatoid arthritis

Front 27

What is the main mediator of the disease, SLE (lupus)?

Main effects:

Back 27

-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.

Front 28

Main symptoms of Lupus:

Back 28

-Vasculitis
-Arthritis
-Swelling

Complement-mediated effects - inflammation and lysis of self sells

Front 29

What is vasculitis?

Back 29

occlusions in small blood vessels - result of neutrophils attaching to them in lupus.

Front 30

Multiple Sclerosis
-mediators
-effects
-results

Back 30

Mediators: Tcells reactive to myelin sheaths around nervous tissue in CNS.

Effects: lesions on the CNS tissue

Results: neurologic dysfunction.

Front 31

What is Rheumatoid arthritis?
-mediators
-effect
-result

Back 31

mediators: auto antibodies to Ig-G

effect: form complexes with Ig-M, deposited in joints.

Result: chronic inflammation of joints. Pain.

Front 32

2 very General treatment strategies for autoimmunity:

Back 32

-Remove the thymus


-Give corticosteroids

Front 33

What is Plasmapheresis?

Back 33

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.

Front 34

What are 2 more-specific treatment options for autoimmune disease?

Back 34

-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.

Front 35

How can Tolerance aid in preventing autoimmunity?

Back 35

Oral eating of antigen induces tolerance, immunologic unresponsiveness.