Autoimmunity

Question 1

autoimmune diseases

Answer 1

“self” antigen is recognized as foreign by immune system and there is a failure of regulatory mechanisms. effector mechanisms include types II,III,IV hypersensitivity reactions.

Question 2

factors contributing to the development of autoimmune diseases

Answer 2

all autoimmune diseases involve the breakdown of T and B cell tolerance and the production of autoantibody an/or inflammatory autoreactive T cells. genetic factors and environmental factors play a part too

Question 3

two-hit hypothesis

Answer 3

genetic susceptibility leads to failure of self-tolerance. then, when a trigger occurs, the autoimmune disease begins.

Question 4

central B cell tolerance

Answer 4

clonal deletion of self-reactive b cells in the bone marrow

Question 5

peripheral b cell tolerance

Answer 5

without cognate T cell help, antigen activated B cells in the T cell zone of a lymph node die by apoptosis. B cells may also become anergic after encounter with soluble antigen, and then will be eliminated by antigen-specific T cell through Fas signalling.

Question 6

central t cell tolerance

Answer 6

normally t cells that bind to self peptides presented by MHC on the thymic cells are deleted. defects in AIRE leads to production of a variety of autoimmune B and T cell responses, and autoimmune polyglandular disease

Question 7

insufficient control of T-cell costimulant

Answer 7

activation of T cells requires both antigen presentation and costimulation (B7/CD28). autoreactive cells may have a lower threshold for activation. allelic variants of CTLA-4, and CD40/CD40L variants (higher levels may lead to more activation)

Question 8

lack of regulatory T cells may contribute to autoimmune disease

Answer 8

CD4+, CD25+, CTLA4+ producing IL4, IL10, and TGFB. require cell contact and CTLA4 for activity. defects in FoxP3, a transcription repressor gene unique to Treg, results in autoimmune disease, mainly in boys.

Question 9

inflammatory Th 17 cells in autoimmune disease

Answer 9

Helper CD4+ T cells that secrete IL17. proinflammatory binds to IL17 receptor, leading to secretion of cytokines and recruitment of inflammatory cells.

Question 10

molecular mimicry

Answer 10

may contribute to role of infections. pathogen-derived peptides structurally similar to a self antigen stimulate a T cell response directed against the self-antigen.

Question 11

infection leading to increased antigen presentation

Answer 11

during infection, Class I and Class II expression may be induced or increased due to interferon gamma production

Question 12

what is the dominant genetic factor affecting susceptibility to autoimmune disease?

Answer 12

HLA!!

Question 13

release of sequestered antigens

Answer 13

trauma to sites of immune privelege: normal entry of naive lymphocytes is prevented but self antigens may be exposed to circulation by wound or infection, and effector cells can gain access.

Question 14

antibody mediated autoimmune diseases

Answer 14

organ-specific and caused by same effector mechanisms as for Type II hypersensitivity reactions

Question 15

hemolytic anemia

Answer 15

IgG autoantibodies bound to Rh or I antigens may promote antibody dependenct cell mediated cytotoxicity or complement fixation

Question 16

graves disease

Answer 16

TSH usually induces breakdown of thyroglobulin, releasing T3 and T4, signalling the pituitary to stop releasing TSH. in graves disease, autoantibodies bind TSH receptor of thyroid cells, mimicking action of TSH so more throid hormones are released

Question 17

myasthenia gravis

Answer 17

ACh binds to ACh receptors on muscle cells, inflow of sodium ions causes contraction. In MG, anto-ACh receptor Ig binds and results in receptor endocytosis and degradation, leading to fewer receptors and decreased sensitivity to stimulation and progressive muscle weakening

Question 18

IgG mediated disease transferring in utero

Answer 18

antibodies can cross the placenta into the fetus. can be cured by plasmapheresis.

Question 19

immune-complex mediated autoimmune diseases

Answer 19

type III hypersensitivity effector mechanisms. immune complexes deposit in tissues, fix complement, leading to influx of inflam cells, resulting in tissue damage.

Question 20

systemic lupus erythematosus (SLE)

Answer 20

immune complexes contain Anti-DNA, anto nucleosome antibodies. Anti-dsDNA titer is diagnostic. butterfly rash, fatigue, headache

Question 21

T-Cell mediated autoimmune diseases

Answer 21

type IV hypersensitivity effector mechanisms. Antigen specific T cells activated by antigen, as well as other immune cells lead to inflam response.

Question 22

juvenile diabetes

Answer 22

type 1 diabetes, insulin dependent. beta cells in pancreas make little to no insulin due to destruction by CD8+ T cells. increased thirst and urination, weight loss, nausea, fatigue.

Question 23

rheumatoid arthritis

Answer 23

antibodies that react with the constant regions of other antibodies and infiltration of the join synovium by inflammatory CD4 and CD8 cells. secretion of TNFa, IL2,6,7, leads to recruitment of effector cells. weakness, fatigue, joint pain

Question 24

multiple sclerosis

Answer 24

chronic organ specific disease. myelin sheath covering cells of spinal cord and brain destroyed due to CD4 T cells which secrete IFN gamma and activate macrophages. autoantibodies to myelin, proteolipid, etc. weakness, tremors, etc

Question 25

celiac disease

Answer 25

IgA or IgG antibodies to tissue transglutaminase

Question 26

treatments for autoimmune diseases

Answer 26

removal of antigen, antibody, or immune complexes. IVIG. NSAIDS, steroids, etc. depletion of immune cells. block interaction of immune cells. repleacement therapy. hormones, diet, exercise

Question 27

rituximab and infliximab

Answer 27

Rheumatoid arthritis drugs. good success rate