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Flashcards in 12 T Cell Tolerance Deck (42):
1

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

false---they are by both

2

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

false---they are by both

3

What do medullary epithelial cells express?

self peptides in the context of MHCI and MHCII

4

What drives thymocyte selection?

affinity for MHC/antigen complex

5

What locations all play roles in thymocyte selection?

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)

6

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

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

7

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

Medullary thymic epithelial cells

8

What drives the promiscuous expression of proteins for thymocyte selection?

transcriptional regulator AIRE

9

What picks up proteins from blood stream for thymocyte selection?

thymus resident dendritic cells

10

What presents periphery self antigens to the thymus?

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

11

Most important mechanisms of peripheral tolerance? [3]

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

12

What mechanisms drive immune privilege? [5]

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

13

What mechanisms drive immune privilege? [5]

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

14

What do medullary epithelial cells express?

self peptides in the context of MHCI and MHCII

15

What drives thymocyte selection?

affinity for MHC/antigen complex

16

What locations all play roles in thymocyte selection?

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)

17

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

B7

18

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

Medullary thymic epithelial cells

19

What drives the promiscuous expression of proteins for thymocyte selection?

transcriptional regulator AIRE

20

What picks up proteins from blood stream for thymocyte selection?

thymus resident dendritic cells

21

What presents periphery self antigens to the thymus?

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

22

Most important mechanisms of peripheral tolerance? [3]

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

23

Damage to an immune privileged organ can cause what?

autoimmunity

24

What mechanisms drive immune privilege? [5]

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

25

What 3 signals are required for Tcell full activation?

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

26

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

signal 1 in absence of signal 2.

27

What is the primary costimulatory molecule for naive T cells?

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

28

What happens to mice deficient in CD28?

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

29

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

B7

30

The simultaneous activation of both the TCR and CD28?

cytokine production, proliferation, and protein expression

31

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

CTLA-4

32

What happens in over expression of CTLA-4?

immune evasion of several types of cnacer

33

What happens in defects of CTLA-4?

autoimmunity

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?

Regulatory T cells

35

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

regulatory T cells

36

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

Regulatory---Naive make IL-2

37

What is the key transcriptional regulator for regulatory T cells?

FOXP3- epigenetically

38

When are regulatory T cells produced?

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

39

What is the purpose of inducible regulatory T cells?

limit damage to surrounding tissue

40

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

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

41

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

multiple autoimmune disorders

42

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

autoimmune disorders