Lecture 23 - Effector Mechanisms in T Cell Responses Flashcards Preview

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Flashcards in Lecture 23 - Effector Mechanisms in T Cell Responses Deck (58):
1

Primary target of cellular immunity

Intracellular pathogens

2

Primary target of humoral immunity

Extracellular pathogens

3

Response to small extracellular pathogens, such as bacteria and fungi

Th17 neutrophilic response

4

Response to large extracellular parasites, eg: helminth worms

Th2-mediated IL-5 and eosinophil response

5

Response to cytosolic intracellular pathogens

CD8+

6

Response to intracellular pathogens in phagocytic compartments

Th1-mediated IFNg responses

7

What does LFA-1 stand for?

Leukocyte function antigen 1

8

Which cells express selectins?

Cells to which T cells will adhere

9

Which cells express E- and P-selectin?

Epithelial cells

10

Which T cell surface molecule binds to E- and P-selectin?

PSGL-1

11

Which selectins do epithelial cells express?

P- and E-selectins

12

Activation signals secreted by epithelial cells

CCL17, CCL27

13

Epithelial cell adhesion molecules

ICAM-1, VCAM-1

14

Which cells express ICAM-1 and VCAM-1?

Endothelial cells

15

What induces epithelial cells to express T cell adhesion molecules?

TNFa, IFNg

16

What detects CCL17 and CCL27?

CCR4 and CCR10

17

What binds ICAM-1?

LFA-1

18

What binds VCAM-1?

VLA-4

19

Factor expressed by endothelial cells in GALT for T cell rolling

MAdCAM-1 and P-selectin

20

What expresses MAdCAM-1 and P-selectin?

Endothelial cells in GALT

21

MAdCAM-1 ligand for rolling

Inactive alpha4 beta7 integrin

22

T cell activation factor in GALT

CCL25 (produced by enterocytes)

23

What expresses CCL25?

Enterocytes.
Activates T cells in GALT

24

Factor expressed by GALT endothelial cells for adhesion

MAdCAM-1

25

MAdCAM-1 ligand for adhesion

Active alpha4 beta7 integrin

26

How is tissue-specific information imprinted in organ-dwelling lymph nodes?

A factor from the organ that the lymph node drains biases T cells to express certain chemokine receptors

27

Example of imprinting of tissue-specific information in an organ-dwelling lymph node
1)
2)
3)

1) In a lymph node that drains the skin, vitamin D metabolites act on dendritic cells and stromal cells
2) DCs, stromal cells secrete factors, cause T cell upregulation of CCR4, CCR10, PSGL-1.
3) T cells migrate to skin

28

Metabolites that imprint on lymph nodes gut addressins

Vitamin A metabolites

29

What causes T cells to differentiate into Th1?
1)
2)
3)
4)
5)

1) Dendritic cell presents antigen to naive T cell on MHCII
2) DC or macrophage releases IL-12
3) NK cell releases IFNg
4) IL-12 activates STAT4 transcription factor
5) IFNg activates STAT1, T-bet transcription factors

30

How does Th1 amplification occur?

Th1 releases IFNg, autostimulates

31

What do STAT1, STAT4 and T-bet do?

Transcription factors activated by IL-12 and IFNg
Lead to Th1 phenotype

32

Th1 functions
1)
2)
3)
4)
5)
6)

1) Macrophage activation
2) Infected cell killing
3) T cell proliferation
4) Differentiation in bone marrow
5) Endothelial activation
6) Chemotactic effects

33

With what do Th1 activate macrophages?

IFNg, CD40L

34

With what do Th1 kill cells?

FasL, LTbeta

35

With what do Th1 induce T cell proliferation?

IL-2

36

With what do Th1 induce differentiation in the bone marrow?

IL-3, GM-CSF

37

With what do Th1 induce endothelial activation?

TNFa, LTalpha

38

With what do Th1 induce chemotaxis?

CXCL2

39

How do naive T cells differentiate into Th2?
1)
2)
3)
4)

1) DC presents antigen to T cell
2) Mast cells (maybe eosinophils) release IL-4
3) IL-4 activates STAT6. Unknown factor activates GATA3
4) Th2 releases IL-4, autostimulates

40

Activated Th2 effects
1)
2)
3)
4)

1) IL-4 biases antibody isotype to IgG, IgE. IgE leads to sensitisation of mast cells
2) IL-4, IL-13 lead to intestinal mucosal secretion, peristalsis
3) IL-5 activates eosinophils
4) IL-4, IL-13 lead to alternative macrophage activation

41

Roles of alternative macrophages

Enhanced fibrosis and tissue repair

42

Transcription factors leading to Th2 phenotype

STAT6, GATA3

43

How are naive T cells biased towards Th17?
1)
2)
3)
4)

1) DC presents antigen, releases IL-1, IL-6. TGFb from other sources
2) IL-6 activates STAT3. TGFb activates RORgammaT.
3) IL-21 is released for autostimulation
4) DC releases IL-23. Th17 is mature

44

Role of IL-17
1)
2)

1) Causes leukocytes and tissue cells to release TNFa, colony stimulating factors, chemokines, IL-1 and IL-6
2) This leads to inflammation, neutrophil response, antimicrobial peptides

45

Effect of IL-23
1)
2)

1) Increases barrier function of epithelial cells
2) Increase in antimicrobial peptides

46

Factors released by Th17
1)
2)
3)

1) IL-17
2) IL-22
3) IL-23

47

Basic CD8+ killing
1)
2)
3)
4)

1) Non-specific attachment
2) Specific recognition
3) Cytoskeletal changes
4) Granule release

48

Perforin
1)
2)

1) Pore-forming enzyme
2) Aids delivery of granzymes and granulysin into target cell

49

Granzyme
1)
2)

1) Family of serine proteases
2) Induces apoptosis in target cell

50

What is serglycin?

Forms a complex with perforin and granzymes

51

How do CD8+ granules kill target cell?
1)
2)
3)
4)
5)
6)

1) Complex of serglycin, granzyme and perforin is released by CD8+ T cell
2) Perforin forms pore, granzyme enters host cell
3) Granzyme B activates pro-caspase 3, BID
4) Truncated BID activates BAX and BAD on mitochondrial surface, disrupts mitochondria. Caspase 3 activates DNAases
5) Cytochrome C released from mitochondria. Causes apoptosis
6) DNAases induce DNA fragmentation

52

What forms a complex with granzyme and perforin?

Serglycin

53

Fas/FasL pathway
1)
2)
3)
4)

For apoptosis of target cell
1) FasL binds Fas on target cell, causing Fas to trimerise.
2) 'Death domain' (intracellular) of Fas recruits FADD, with death effector domain (DED)
3) DED recruits pro-caspase 8
4) Pro-caspase 8 accumulation leads to activation, apoptosis

54

What plays a major role in eliminating unwanted T cells?

Death via the Fas/FasL pathway

55

What do mutations in the Fas/FasL pathway lead to?

Autoimmune lymphoproliferative disease

56

What causes autoimmune lymphoproliferative disease?

Mutations in the Fas/FasL pathway

57

Where do CD4 and CD8 T cells sit with regards to site of infection?

CD8+ sit next to infected cells
CD4+ sit further away from site of infection

58

What can activate Th IFNg release?

Only professional APCs