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Immunology > Lecture 23 - Effector Mechanisms in T Cell Responses > Flashcards

Lecture 23 - Effector Mechanisms in T Cell Responses Flashcards

1
Q

Primary target of cellular immunity

A

Intracellular pathogens

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2
Q

Primary target of humoral immunity

A

Extracellular pathogens

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3
Q

Response to small extracellular pathogens, such as bacteria and fungi

A

Th17 neutrophilic response

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4
Q

Response to large extracellular parasites, eg: helminth worms

A

Th2-mediated IL-5 and eosinophil response

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5
Q

Response to cytosolic intracellular pathogens

A

CD8+

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6
Q

Response to intracellular pathogens in phagocytic compartments

A

Th1-mediated IFNg responses

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7
Q

What does LFA-1 stand for?

A

Leukocyte function antigen 1

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8
Q

Which cells express selectins?

A

Cells to which T cells will adhere

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9
Q

Which cells express E- and P-selectin?

A

Epithelial cells

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10
Q

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

A

PSGL-1

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11
Q

Which selectins do epithelial cells express?

A

P- and E-selectins

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12
Q

Activation signals secreted by epithelial cells

A

CCL17, CCL27

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13
Q

Epithelial cell adhesion molecules

A

ICAM-1, VCAM-1

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14
Q

Which cells express ICAM-1 and VCAM-1?

A

Endothelial cells

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15
Q

What induces epithelial cells to express T cell adhesion molecules?

A

TNFa, IFNg

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16
Q

What detects CCL17 and CCL27?

A

CCR4 and CCR10

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17
Q

What binds ICAM-1?

A

LFA-1

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18
Q

What binds VCAM-1?

A

VLA-4

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19
Q

Factor expressed by endothelial cells in GALT for T cell rolling

A

MAdCAM-1 and P-selectin

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20
Q

What expresses MAdCAM-1 and P-selectin?

A

Endothelial cells in GALT

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21
Q

MAdCAM-1 ligand for rolling

A

Inactive alpha4 beta7 integrin

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22
Q

T cell activation factor in GALT

A

CCL25 (produced by enterocytes)

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23
Q

What expresses CCL25?

A

Enterocytes.

Activates T cells in GALT

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24
Q

Factor expressed by GALT endothelial cells for adhesion

A

MAdCAM-1

25
Q

MAdCAM-1 ligand for adhesion

A

Active alpha4 beta7 integrin

26
Q

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

A

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

27
Q

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

A

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
Q

Metabolites that imprint on lymph nodes gut addressins

A

Vitamin A metabolites

29
Q 
What causes T cells to differentiate into Th1?
1)
2)
3)
4)
5)
A

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
Q

How does Th1 amplification occur?

A

Th1 releases IFNg, autostimulates

31
Q

What do STAT1, STAT4 and T-bet do?

A

Transcription factors activated by IL-12 and IFNg

Lead to Th1 phenotype

32
Q 
Th1 functions
1)
2)
3)
4)
5)
6)
A

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

33
Q

With what do Th1 activate macrophages?

A

IFNg, CD40L

34
Q

With what do Th1 kill cells?

A

FasL, LTbeta

35
Q

With what do Th1 induce T cell proliferation?

A

IL-2

36
Q

With what do Th1 induce differentiation in the bone marrow?

A

IL-3, GM-CSF

37
Q

With what do Th1 induce endothelial activation?

A

TNFa, LTalpha

38
Q

With what do Th1 induce chemotaxis?

A

CXCL2

39
Q 
How do naive T cells differentiate into Th2?
1)
2)
3)
4)
A

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
Q 
Activated Th2 effects
1)
2)
3)
4)
A

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
Q

Roles of alternative macrophages

A

Enhanced fibrosis and tissue repair

42
Q

Transcription factors leading to Th2 phenotype

A

STAT6, GATA3

43
Q 
How are naive T cells biased towards Th17?
1)
2)
3)
4)
A

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
Q

Role of IL-17
1)
2)

A

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
Q

Effect of IL-23
1)
2)

A

1) Increases barrier function of epithelial cells

2) Increase in antimicrobial peptides

46
Q

Factors released by Th17
1)
2)
3)

A

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

47
Q 
Basic CD8+ killing
1)
2)
3)
4)
A

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

48
Q

Perforin
1)
2)

A

1) Pore-forming enzyme

2) Aids delivery of granzymes and granulysin into target cell

49
Q

Granzyme
1)
2)

A

1) Family of serine proteases

2) Induces apoptosis in target cell

50
Q

What is serglycin?

A

Forms a complex with perforin and granzymes

51
Q 
How do CD8+ granules kill target cell?
1)
2)
3)
4)
5)
6)
A

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
Q

What forms a complex with granzyme and perforin?

A

Serglycin

53
Q 
Fas/FasL pathway
1)
2)
3)
4)
A

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
Q

What plays a major role in eliminating unwanted T cells?

A

Death via the Fas/FasL pathway

55
Q

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

A

Autoimmune lymphoproliferative disease

56
Q

What causes autoimmune lymphoproliferative disease?

A

Mutations in the Fas/FasL pathway

57
Q

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

A

CD8+ sit next to infected cells

CD4+ sit further away from site of infection

58
Q

What can activate Th IFNg release?

A

Only professional APCs

Immunology (30 decks)

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