T Cell Tolerance (Exam 3)

Question 1

Term for unresponsiveness to antigen induced by previous exposure to that antigen.

Answer 1

tolerance

Question 2

________ is an antigen that results in tolerance while _______ is an antigen that results in immunity.

Answer 2

tolerogen
immunogen

Question 3

How can the same antigen be both tolerogenic and immunogenic?

Answer 3

dependent on how naive cell first encounters antigen

Question 4

When a lymphocyte recognizes _______, it leads to proliferation and differentiation. When a lymphocyte recognizes _______, it leads to anergy or deletion.

Answer 4

microbes
self-antigen

Question 5

________ is the first layer of removing self-reactive naive lymphocytes before entering circulation. ________ rids of mature T cells in the periphery that have escaped previous answer.

Answer 5

central tolerance
periphery tolerance

Question 6

Where does central tolerance occur? Peripheral tolerance?

Answer 6

central: primary lymphoid organs
peripheral: generative organs

Question 7

In central tolerance, if naive T cells are self-reactive, what are the possible outcomes?

Answer 7

1. negative selection –> anergy or deletion
2. made into regulatory T cells

Question 8

What is the function of regulatory T cells?

Answer 8

leave thymus and inhibit self-reactive responses in periphery

Question 9

What 3 fates can occur with self-reactive T cells in peripheral tolerance?

Answer 9

1. anergy
2. suppression (activation blocked by regulatory T cells)
3. deletion (apoptosis)

Question 10

When self-reactive T cells receive an inactivating signal and become functionally unresponsive it is called ________.

Answer 10

anergy

Question 11

What are the two inhibitory receptors which inhibit T cell responses?

Answer 11

CTLA-4
PD-1

Question 12

What 2 mechanisms does CTLA-4 use to inhibit T cell response?

Answer 12

1. signaling block
2. reduce B7 availability

Question 13

How is a T cell response inhibited by CTLA-4 acting as a signaling block?

Answer 13

CTLA-4 activates B7 phosphatase –> phosphate removed from TCR = T cell response inhibited

Question 14

How does CTLA-4 inhibit T cell response by reducing B7 availability?

Answer 14

binds to B7 on APCs so CD28 on T cells cannot bind it

Question 15

______ is upregulated on T cells after chronic exposure to antigen.

Answer 15

PD-1

Question 16

AIRE protein stands for __________.

Answer 16

autoimmune regulator

Question 17

What is the function of AIRE protein?

Answer 17

part of central tolerance so self-proteins from tissues can be brought to thymus to test T cell self-reactiveness

Question 18

(T/F) AIRE is a transcription factor expressed by thymic medullary epithelial cells.

Answer 18

True

Question 19

What transcription factor is critical for development and function of T cells?

Answer 19

FoxP3

Question 20

Function of FoxP3

Answer 20

transcription factor which can inhibit T cell responses

Question 21

FoxP3 requires _____ and ____ cytokines which induce regulatory T cell development and FoxP3 expression.

Answer 21

TGF-B
IL-2

Question 22

______ is a death receptor on T cells which is upregulated with repeated antigen stimulation. ______ is a ligand of the receptor.

Answer 22

Fas
FasL

Question 23

What is the “signal for death”?

Answer 23

Fas ligand

Question 24

How do Fas receptor and Fas ligand lead to cell death?

Answer 24

proteins assemble and cleave caspase-8 –> cleavage of other caspases = apoptosis

Question 25

“Death by neglect” when activated T cells don’t get the signal to survive which leads to apoptosis is considered __________ cell death.

Answer 25

passive cell death

Question 26

When activated T cells receive too much stimulation, they undergo apoptosis which is called ________ cell death.

Answer 26

activation-induced cell death

Question 27

Passive cell death is ______ mediated while activation-induced cell death is ______ mediated.

Answer 27

Bim-mediated
Fas-mediated

Question 28

What activates Bim in passive cell death? How does it cause apoptosis?

Answer 28

-activated by lack of costimulatory molecule

-activated Bim –> mitochondria cytochrome C + caspase-9 activated = apoptosis