breakout 7

Question 1

central tolerance occurs during

Answer 1

lymphocyte development

Question 2

in central tolerance, B cells in

Answer 2

bone marrow

Question 3

in central tolerance, T cells in

Answer 3

thymus

Question 4

peripheral tolerance

Answer 4

occurs in other part of the body, including lymph nodes

Question 5

in peripheral tolerance, B cells can become

Answer 5

anergic

Question 6

in peripheral tolerance, T cells can become

Answer 6

anergic or undergo apoptosis

Question 7

anergizing BCR signaling

Answer 7

hypophosphorylated ITAM inhibits NF-kB

Question 8

deleting BCR signaling

Answer 8

hyperphosphorylated ITAM leads to increase ERK1/2

Question 9

In the absence of T cell help, B cells that recognize self

Answer 9

antigen in periphery become anergic bc they have no survival signals from T cell

Question 10

Central T lymphocyte tolerance occurs in

Answer 10

thymus

Question 11

central T lymphocyte tolerance involves

Answer 11

immature “double positive” T cells and strong recognition to antigens results in apoptosis

Question 12

T cells that recognize self antigen in thymus undergo

Answer 12

apoptosis

Question 13

antigen presentation, in absence of co-stim by B7-CD28 results in

Answer 13

T cell anergy

Question 14

why is co-stim needed for T cells?

Answer 14

• B7-CD28 co-stim is necessary to stabilize IL-2 production
• IL-2 necessary for T cell survival

Question 15

mechanisms of peripheral T cell tolerance:
anergy and costimulation
CD28 : CD80/86 interaction

Answer 15

increases IL-2 transcription
stabilizes IL-2 transcripts

Question 16

results of CD28:CD80/86 interaction

Answer 16

self reactive cell receives:
no CD28 stimulation
lack of sufficient IL-2
anergized T cell

Question 17

Mechanisms of Peripheral T cell tolerance:
deletion and overstimulation

Answer 17

excessive signaling of TCR by self antigen leads to induction of apoptosis thorugh Fas/FasL interactions

Question 18

Peripheral T cell tolerance:
regulatory T cells

Answer 18

subpopulation of T cells that can inhibit activation of T cells that secrete IL-10 and TGF-beta to suppress inflammation

Question 19

what could tregs be used for

Answer 19

autoimmune diseases and transplant rejection

Question 20

B cells center tolerance:
anergy -> antigen type, conc, phosphorylation, signaling reponse

Answer 20

soluble, low, hypo, loss of NFkB

Question 21

B cells central tolerance:
apoptosis -> antigen type, conc, phosphorylation, signaling, response

Answer 21

multi-variant, high, hyper, ERK1/2

Question 22

B cells peripheral tolerance:
anergy -> survival signal, response

Answer 22

lack of BAFF, Lack of T cell help

Question 23

T cells central tolerance:
apoptosis -> cell type, antigen binding

Answer 23

CD4+CD8+ T cells and tight binding

Question 24

T cells peripheral tolerance:
anergy -> survival signal, response

Answer 24

reduced IL-2 and lack of T cell help

Question 25

T cells peripheral tolerance:
apoptosis -> survival signal, response

Answer 25

Fas/FasL and repeated stimlation of target organ

Question 26

T cells peripheral tolerance:
Treg -> survival signal, response

Answer 26

suppressed with IL-10 and TGF-beta
self-reactive Tregs destroys self-reactive T cells

Question 27

APECED

Answer 27

autoimmune polyendocrinopathy candidiasis ectodermal dystrophy
* inherited antoimmune polyglandular syndrome type I

Question 28

APECED symptoms are

Answer 28

hypoparathyroidism
adrenocortical insufficiency
tubulo-interstitial nephritis
candidiasis
enamel dysplasia

Question 29

what causes APECED?

Answer 29

defects in AIRE (autoimmune regulator)

Question 30

what is AIRE?

Answer 30

protein expressed in thymus (promote centeral tolerance of T cells)
increases expression of tissue-specific genes in medullary thymic epithelial cells

Question 31

what are the 3 ways AIRE promotes tissue-specific gene expression

Answer 31

1. promotes chromatin remodeling
2. directly acts as transcription factor
3. interacts with protein complexes on “stalled” promoters

Question 32

how does AIRE lead to deletion of thymocytes

Answer 32

presented on HLA class I
presented on HLA class II of neighboring thymic dendritic cells