Microreview123(Tolerance And Autoimmunity)

Front 1

Define tolerance. Why is it medically important?

Back 1

Tolerance is the unresponsiveness of the immune system to antigen developed upon previous exposure to that antigen. Self tolerance is tolerance to self antigens and autoimmune diseases occur when self tolerance fails.

Front 2

Where do the most self tolerance sensitive stages of lymphocytic maturation occur and why? What is this known as?

Back 2

Central lymphoid organs thymus(T cells) and bone marrow(B cells) have high concentrations of self antigens to present to immature lymphocytes. This is central tolerance.

Front 3

What is the principal mechanism of central tolerance?

Back 3

Apoptotic cell death(clonal deletion).

Front 4

What is the principal mechanism of central tolerance?

Back 4

Apoptotic cell death(clonal deletion).

Front 5

In central tolerance, immature lymphocytes with high affinity receptors for self antigens are deleted. What is this called?

Back 5

Negative selection.

Front 6

The autoimmune regulator(AIRE) gene encodes a protein that stimulates expression of endocrine self antigens in thymic epithelial cells. If there is a mutation in the AIRE gene, what disease results?

Back 6

Failure of negative selection leads to immune mediated injury to multiple endocrine organs(autoimmune polyendocrine syndrome).

Front 7

Where does peripheral tolerance occur. What mechanisms mediate this?

Back 7

Peripheral tolerance occurs outside the thymus/bone marrow and results from triggering of antigen receptor in the absence of costimulation or repeated self antigen stimulation.

Front 8

What are 2 requirements for CD4 helper T cell activation?

Back 8

T cell receptor(Tcell receptor) must bind to MHC(MHC11) with the antigen peptide and T cell CD28 must bind to APC B7 molecule for costimulation.

Front 9

What happens when peptide antigens are presented to CD4+ T cells by APCs deficient in costimulators. Why is this important?

Back 9

Anergy or unresponsiveness. Clonal anergy refers to unresponsiveness of self reactive T cells and is the mechanism of self tolerance.

Front 10

What happens when peptide antigens are presented to CD4+ T cells by APCs deficient in costimulators. Why is this important?

Back 10

Anergy or unresponsiveness. Clonal anergy refers to unresponsiveness of self reactive T cells and is the mechanism of self tolerance.

Front 11

Anergic T cells are defined as those that fail to produce which growth factor?

Back 11

Interleukin 2(IL-2)

Front 12

What differentiates clonal ignorance from clonal anergy?

Back 12

In clonal ignorance, self reactive T cells ignore self antigens but are still functional. Clonal anergy results in permanent antigen nonresponsiveness.

Front 13

Which T cell coreceptor delivers inhibitory signals when it interacts with B7?

Back 13

Cytotoxic T lymphocyte antigen 4 (CTLA-4)(either lack of costimulation or interaction of CTLA-4 B7 at the same time as antigen results in T cell anergy.

Front 14

Repeated stimulation of CD4+ T cells by antigen results in the coexpression of which receptor and ligand for activation induced cell death?

Back 14

Fas/FasL(which activate the caspase cascade vis caspase 8).

Front 15

What lineage of cell may also induce T cell tolerance?

Back 15

Regulatory T cells(exact type unknown) are also thought to play a role in tolerance>

Front 16

Central B tolerance is most likely to occur with a central antigen of what structure. Name 2 examples.

Back 16

Multivalent antigens bind and crosslink many receptors on each specific B cell. Examples include membane molecules, DNA.

Front 17

What is the process by which immature B cells that encounter self antigen in bone marrow acquire new antigen specificity for their B cell receptors?

Back 17

Receptor editing allows B cells to ignore self antigens.

Front 18

What is the fate of mature B cells that recognize self antigens in peripheral tissue in the absence of specific helper T cells?

Back 18

Anergy with exclusion from lymphoid follicles.

Front 19

What happens when IgG produced by B cells forms complexes with antigen and binds to their own Fc receptors?

Back 19

Inhibitory feedback.

Front 20

What happens when IgG produced by B cells forms complexes with antigen and binds to their own Fc receptors?

Back 20

Inhibitory feedback.

Front 21

What are the majorfactors that contribute to the development of autoimmunity?

Back 21

Genetic susceptibility, environmental factors(mainly bacteria, viruses), hormonal factors(majority occur in women).

Front 22

Which family of genes is most strongly associated with autoimmunity?

Back 22

Human leukocyte antigen(HLA)

Front 23

What is epitope spreading?

Back 23

When autoimmune reactions against a self antigen cause release of other self antigens from damaged tissue resulting in exacerbation of disease.

Front 24

Define molecular mimicry.

Back 24

Antigens of a microbe induce production of antibodies that cross react with self antigens.

Front 25

How might inflammation, ischemic injury, or trauma lead to autoimmunity?

Back 25

Exposure of self antigens that arenormally concealed from immune system.

Front 26

What are examples of anatomically sequestered antigens?

Back 26

Intraocular proteins, sperm proteins, CNS proteins such as myelin.

Front 27

What are examples of anatomically sequestered antigens?

Back 27

Intraocular proteins, sperm proteins, CNS proteins such as myelin.

Front 28

What are examples of anatomically sequestered antigens?

Back 28

Intraocular proteins, sperm proteins, CNS proteins such as myelin.

Front 29

What are examples of anatomically sequestered antigens?

Back 29

Intraocular proteins, sperm proteins, CNS proteins such as myelin.

Front 30

Which autoimmune diseases are due to antibodies against receptors?

Back 30

Myasthenia gravis, Graves disease, diabetes type 1, Lambert Eaton.

Front 31

What is an example of a T cell mediated autoimmune disease?

Back 31

Multiple sclerosis, celiac disease(even though autoantibodies are found).

Front 32

Which organisms are associated with Reiter's syndrome?

Back 32

Chlamydia, Shigella, and other enteric pathogens.

Front 33

Which syndrome is associated with diarrhea caused by campylobacter jejuni and antibodies against myelin protein?

Back 33

Guillain-Barre'

Front 34

Which syndrome is associated with diarrhea caused by campylobacter jejuni and antibodies against myelin protein?

Back 34

Guillain-Barre'

Front 35

Which disease is associated with autoantibodies formed against IgG in joints?

Back 35

Rheumatoid arthritis, rheumatoid factor is the anti IgG antibody.

Front 36

What antibodies arefound in systemic lupus erythematous?

Back 36

Anti-double stranded DNA, anti Smith(nuclear ribonucleoproteins).

Front 37

What drugs are associated with drug induced lupus? What is the autoantibody involved in pathogenesis?

Back 37

Hydralazine, procainamide, quinidine, isoniazid. Antihistone quantibody.

Front 38

What disease is associated with anti SS-B(La) and anti SS-A(RO) antibodies? What are the clinical syndromes?

Back 38

SJogren's syndrome. It has a classic triad of dry eyes(xeropthalmia), dry mouth(xerostomia) and rheumatoid arthritis.

Front 39

Scleroderma results in marked fibrosis of tissue. What are the 2 forms of scleroderma and what are the autoantibodies associated with each one?

Back 39

Diffuse: involves the skin and visceral organs such as the lungs(pulmonary fibrosis) and kidney vasculature(kidney failure and death). Anti-Scl-70 antibodies.

Front 40

Which autoimmue disorder targets hair follicles?

Back 40

Alopecia areata leads to variable hair loss.

Front 41

Goodpasture's syndrome unlike most autoimmune disorders is more prevalent in men. Name the autoantibody it targets and the resulting symptoms?

Back 41

Targets the glomerular and alveolar basement membranes leading to hemoptysis and hemoturia.

Front 42

In Goodpature's what immunofluorescence pattern is seen on the glomerular basement membrane?

Back 42

Linear pattern

Front 43

Myositis, such as polymyositis and dermatomyositis, may be associated with what antibody?

Back 43

Anti jo, antibody(Jo1 is tRNA synthase) is often seen in polymyositis with interstitial lung disease.

Front 44

Autoimmune hepatitis is a rare autoimmune disease. What antibody is detected?

Back 44

Antismooth muscle antibody.

Front 45

For each of the HLA allele, list associated autoimmune diseases.
DR2
DR3
DR4

Back 45

DR2-Multiple sclerosis, Goodpasture's and SLE
DR3-SLE, diabetes mellitus Type 1, Celiac sprue
DR4- Diabetes mellitus type 1, pemphigus vulgaris, rheumatoid arthritis

Front 46

What are HLA-B27 associated disorders?

Back 46

Ankylosing spondylitis, Reiter's inflammatory bowel disease, psoriatic arthritis.

Front 47

Name 2 autoimmune diseases and one bacterial infection associated with an increased risk for B cell mucosal associated lymphoid tissue(MALT) lymphoma.

Back 47

Sjogren's, Hashimoto's thyroiditis, and helicobacter pylori infection.

Front 48

What autoimmune disease is linked with enteropathy associated T cell lymphoma.

Back 48

Celiac sprue