12 T Cell Tolerance

Question 1

True or false? self reactive t cells are controlled by central but not peripheral tolerance?

Answer 1

false—they are by both

Question 2

True or false? self reactive t cells are controlled by central but not peripheral tolerance?

Answer 2

false—they are by both

Question 3

What do medullary epithelial cells express?

Answer 3

self peptides in the context of MHCI and MHCII

Question 4

What drives thymocyte selection?

Answer 4

affinity for MHC/antigen complex

Question 5

What locations all play roles in thymocyte selection?

Answer 5

cortical epithelial cells, medullary epithelial cells and resident dendritic cells—(basically anywhere in the thymus when there is a functional TCR alpha and beta presented)

Question 6

Mice with deficient MHC class II can’t produce what?

Answer 6

CD4 Tcells–defects in ability to activate CD4 thymocytes during selection

Question 7

What area of the thymus presents the largest number of proteins from the human body for selection?

Answer 7

Medullary thymic epithelial cells

Question 8

What drives the promiscuous expression of proteins for thymocyte selection?

Answer 8

transcriptional regulator AIRE

Question 9

What picks up proteins from blood stream for thymocyte selection?

Answer 9

thymus resident dendritic cells

Question 10

What presents periphery self antigens to the thymus?

Answer 10

Peripheral dendritic cells (food antigens and commensal bacteria antigens too)

Question 11

Most important mechanisms of peripheral tolerance? [3]

Answer 11

immune privilege
costimulation —>anergy and cell death
regulatory T-cells

Question 12

What mechanisms drive immune privilege? [5]

Answer 12

1. Physical barriers
2. low expression of MHC
3. Expression of suppressive cytokines
4. Expression of Fas ligands
5. Increased number of regulatory T-cells

Question 13

What mechanisms drive immune privilege? [5]

Answer 13

1. Physical barriers
2. low expression of MHC
3. Expression of suppressive cytokines
4. Expression of Fas ligands
5. Increased number of regulatory T-cells

Question 14

What do medullary epithelial cells express?

Answer 14

self peptides in the context of MHCI and MHCII

Question 15

What drives thymocyte selection?

Answer 15

affinity for MHC/antigen complex

Question 16

What locations all play roles in thymocyte selection?

Answer 16

cortical epithelial cells, medullary epithelial cells and resident dendritic cells—(basically anywhere in the thymus when there is a functional TCR alpha and beta presented)

Question 17

Infections and inflammation leads to up regulation of what in antigen presenting cells? [costimulatory protein with CD28]

Answer 17

B7

Question 18

What area of the thymus presents the largest number of proteins from the human body for selection?

Answer 18

Medullary thymic epithelial cells

Question 19

What drives the promiscuous expression of proteins for thymocyte selection?

Answer 19

transcriptional regulator AIRE

Question 20

What picks up proteins from blood stream for thymocyte selection?

Answer 20

thymus resident dendritic cells

Question 21

What presents periphery self antigens to the thymus?

Answer 21

Peripheral dendritic cells (food antigens and commensal bacteria antigens too)

Question 22

Most important mechanisms of peripheral tolerance? [3]

Answer 22

immune privilege
costimulation —>anergy and cell death
regulatory T-cells

Question 23

Damage to an immune privileged organ can cause what?

Answer 23

autoimmunity

Question 24

What mechanisms drive immune privilege? [5]

Answer 24

1. Physical barriers
2. low expression of MHC
3. Expression of suppressive cytokines
4. Expression of Fas ligands
5. Increased number of regulatory T-cells

Question 25

What 3 signals are required for Tcell full activation?

Answer 25

1: TCR/co-receptors--specificity 2: costimulatory receptors----suppress auto-reactivity 3: cytokines---differentiation

Question 26

What signal in absence of the what other signal causes cell death or anergy in the T cell?

Answer 26

signal 1 in absence of signal 2.

Question 27

What is the primary costimulatory molecule for naive T cells?

Answer 27

CD28--activated upon binding B7-1 and B7-2

Question 28

What happens to mice deficient in CD28?

Answer 28

normal early responses to infection, but do not have T cell expansion, differentiation and function

Question 29

Infections and inflammation leads to up regulation of what in antigen presenting cells? [costimulatory protein with CD28]

Answer 29

B7

Question 30

The simultaneous activation of both the TCR and CD28?

Answer 30

cytokine production, proliferation, and protein expression

Question 31

What protein is expressed several days after initial TCR/CD28 activation, binds B7, and inhibits CD28 function?

Answer 31

CTLA-4

Question 32

What happens in over expression of CTLA-4?

Answer 32

immune evasion of several types of cnacer

Question 33

What happens in defects of CTLA-4?

Answer 33

autoimmunity

Question 34

what are critical for suppressing T cell responses before and following infection, control auto reactive tells and shut down pathogen specific T cell responses?

Answer 34

Regulatory T cells

Question 35

Do naive CD4 T cells or Regulatory T cells have a stronger reactivity to self peptide- MHC class II?

Answer 35

regulatory T cells

Question 36

Do naive CD4 T cells or regulatory T cells make cytokines IL-10 and TGF beta?

Answer 36

Regulatory---Naive make IL-2

Question 37

What is the key transcriptional regulator for regulatory T cells?

Answer 37

FOXP3- epigenetically

Question 38

When are regulatory T cells produced?

Answer 38

during positive and negative selection in the thymus---T cells with a moderate level of self reactivity differentiate into regulatory T cells

Question 39

What is the purpose of inducible regulatory T cells?

Answer 39

limit damage to surrounding tissue

Question 40

What are the 6 mechanisms regulatory T cells suppress effector T cell function?

Answer 40

1. direct inhibition of DC via CTLA4 2. Production of suppressive cytokines 3. Binding of IL-2 by CD25 4. Direct lysis of effector T cells 5. Eliminate extracellular ATP, produce adenosine 6. Forming Gap junctions with effector T cells

Question 41

Overexpression of inflammatory cytokines or under expression of suppressive cytokines can cause??

Answer 41

multiple autoimmune disorders

Question 42

Defects in proteins required for controlling central and peripheral tolerance can also drive the initiation and progression of what?

Answer 42

autoimmune disorders