Immunological Tolerance and Autoimmunity

Question 1

what are the markers of natural Treg?

Answer 1

CD4+CD25+++FoxP3+ and CTLA-4

Question 2

what IL is critical for the survival and functional competence of Treg?

Answer 2

IL-2 (also FoxP3)

Question 3

TGF-B + IL-6 + RA results in expression of RORyt and development of what cell?

Answer 3

Th17

*DCs produce RA

Question 4

TGF-B + IL-2 results in development of what cell?

Answer 4

iTreg

Question 5

where are natural Treg cells generated?

Answer 5

thymus

Question 6

where are iTreg cells produced?

Answer 6

LNs, GI

Question 7

Cytokines IL-4, IL-10, and TGF-B are secreted by Treg, what is the result in APC?

Answer 7

decrease: CD40, CD80/86, IL-12
increase: IL-10

Question 8

anergy is induced without adequate costimulation upon Ag recognition from:

Answer 8

CD80:CD28

Question 9

what cells express CTLA-4 and PD-1 after Ag stimulation?

Answer 9

CD4+ and CD8+

Question 10

what are the receptors in the extrinsic pathway of apoptosis?

Answer 10

Fas (CD95), TNF

Question 11

what initiator caspase is involved in the intrinsic pathway of apoptosis?

Answer 11

caspase 9

Question 12

what initiator caspase in involved in the extrinsic pathway of apoptosis?

Answer 12

caspase 8

Question 13

in peripheral B cell tolerance, what inhibitory receptor is Pylated by Lyn and recruits SHP-1 tyrosine phosphatase to attenuate BCR signaling?

Answer 13

CD22

defects in Lyn, SHP-1, CD22 = autoimmunity

Question 14

tolerance to commensal microbes, uptake: GALT, Th17, Th1, barrier function, REGIIIy

Answer 14

unclassified bacteria

Question 15

tolerance to commensal microbes, uptake: Treg, IL-10, REGIIIy

Answer 15

beneficial bacteria

Question 16

tolerance to commensal microbes, inhibition: Treg, IL-10, REGIIIy

Answer 16

pathobionts

Question 17

mutation in AIRE

Answer 17

autoimmune polyendocrine syndrome (APS)

AIRE is a TF and regulates expression of TRAs; decreased expression of peripheral tissues of self-Ags in medullary thymic epithelial cells

*central

Question 18

mutation in C4

Answer 18

SLE

Question 19

mutation in CTLA-4

enlarged LNs and spleen

Answer 19

CLTA-4 polymorphisms; T1DM, Graves’ disease

Question 20

mutation in Fas/FasL

Answer 20

autoimmune lympho-proliferative syndrome (ALPS)

Question 21

mutation in FoxP3

Answer 21

IPEX

Question 22

mutation in IL-2; IL-2Ra/B

Answer 22

no known disease; defective development, survival or function of regulatory T cells

Question 23

mutation in SHP-1

Answer 23

no known disease; failure of negative regulation of B cells

Question 24

what cells function as APCs for developing T cells, and express peripheral tissue-restricted self-As?

Answer 24

medullary thymic epithelial cells

Question 25

what is the cell-intrinsic function of CTLA-4?

Answer 25

inhibitory signals delivered to T cell, terminates further activation

Question 26

what is the cell-extrinsic action of CTLA-4?

Answer 26

binding to B7 on APC renders CD28 unavailable to activate T cell

Question 27

HLA-B27

Answer 27

ankylosing spondylitis

Question 28

HLA-DRB1

Answer 28

RA, T1DM

Question 29

rheumatic fever, MS

Answer 29

molecular mimicry RF: strep cross-reacts w/ cardiac myosin MS: T cells react w/ myelin basic pro and peps from EBV, influenza, HPV

Question 30

polyclonal activation of auto reactive lymphocytes in the cytokine field

Answer 30

polyclonal (bystander) activation

Question 31

release of sequestered Ags (DAMPs)

Answer 31

release of previously sequestered Ags

Question 32

what type of hypersensitivity is IBS?

Answer 32

Type IV

Question 33

what are the clinical manifestations of SLE?

Answer 33

rashes, arthritis, glomerulonephritis

Question 34

what are the most frequent auto-Abs in SLE?

Answer 34

anti-DNA Abs form IC that are responsible for glomerulonephritis, arthritis, vasculitis of small arteries

Question 35

patients with RA have circulating IgG or IgM called rheumatoid factor, what do they react with?

Answer 35

Fc portion of circulating IgG

Question 36

what cells are involved in RA?

Answer 36

Th1, Th17, activated B cells, plasma cells, Mo