Lecture 23 - Effector Mechanisms in T Cell Responses

Question 1

Primary target of cellular immunity

Answer 1

Intracellular pathogens

Question 2

Primary target of humoral immunity

Answer 2

Extracellular pathogens

Question 3

Response to small extracellular pathogens, such as bacteria and fungi

Answer 3

Th17 neutrophilic response

Question 4

Response to large extracellular parasites, eg: helminth worms

Answer 4

Th2-mediated IL-5 and eosinophil response

Question 5

Response to cytosolic intracellular pathogens

Answer 5

CD8+

Question 6

Response to intracellular pathogens in phagocytic compartments

Answer 6

Th1-mediated IFNg responses

Question 7

What does LFA-1 stand for?

Answer 7

Leukocyte function antigen 1

Question 8

Which cells express selectins?

Answer 8

Cells to which T cells will adhere

Question 9

Which cells express E- and P-selectin?

Answer 9

Epithelial cells

Question 10

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

Answer 10

PSGL-1

Question 11

Which selectins do epithelial cells express?

Answer 11

P- and E-selectins

Question 12

Activation signals secreted by epithelial cells

Answer 12

CCL17, CCL27

Question 13

Epithelial cell adhesion molecules

Answer 13

ICAM-1, VCAM-1

Question 14

Which cells express ICAM-1 and VCAM-1?

Answer 14

Endothelial cells

Question 15

What induces epithelial cells to express T cell adhesion molecules?

Answer 15

TNFa, IFNg

Question 16

What detects CCL17 and CCL27?

Answer 16

CCR4 and CCR10

Question 17

What binds ICAM-1?

Answer 17

LFA-1

Question 18

What binds VCAM-1?

Answer 18

VLA-4

Question 19

Factor expressed by endothelial cells in GALT for T cell rolling

Answer 19

MAdCAM-1 and P-selectin

Question 20

What expresses MAdCAM-1 and P-selectin?

Answer 20

Endothelial cells in GALT

Question 21

MAdCAM-1 ligand for rolling

Answer 21

Inactive alpha4 beta7 integrin

Question 22

T cell activation factor in GALT

Answer 22

CCL25 (produced by enterocytes)

Question 23

What expresses CCL25?

Answer 23

Enterocytes.

Activates T cells in GALT

Question 24

Factor expressed by GALT endothelial cells for adhesion

Answer 24

MAdCAM-1

Question 25

MAdCAM-1 ligand for adhesion

Answer 25

Active alpha4 beta7 integrin

Question 26

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

Answer 26

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

Question 27

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

Answer 27

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

Question 28

Metabolites that imprint on lymph nodes gut addressins

Answer 28

Vitamin A metabolites

Question 29

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

Answer 29

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

Question 30

How does Th1 amplification occur?

Answer 30

Th1 releases IFNg, autostimulates

Question 31

What do STAT1, STAT4 and T-bet do?

Answer 31

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

Question 32

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

Answer 32

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

Question 33

With what do Th1 activate macrophages?

Answer 33

IFNg, CD40L

Question 34

With what do Th1 kill cells?

Answer 34

FasL, LTbeta

Question 35

With what do Th1 induce T cell proliferation?

Answer 35

IL-2

Question 36

With what do Th1 induce differentiation in the bone marrow?

Answer 36

IL-3, GM-CSF

Question 37

With what do Th1 induce endothelial activation?

Answer 37

TNFa, LTalpha

Question 38

With what do Th1 induce chemotaxis?

Answer 38

CXCL2

Question 39

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

Answer 39

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

Question 40

``` Activated Th2 effects 1) 2) 3) 4) ```

Answer 40

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

Question 41

Roles of alternative macrophages

Answer 41

Enhanced fibrosis and tissue repair

Question 42

Transcription factors leading to Th2 phenotype

Answer 42

STAT6, GATA3

Question 43

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

Answer 43

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

Question 44

Role of IL-17 1) 2)

Answer 44

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

Question 45

Effect of IL-23 1) 2)

Answer 45

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

Question 46

Factors released by Th17 1) 2) 3)

Answer 46

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

Question 47

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

Answer 47

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

Question 48

Perforin 1) 2)

Answer 48

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

Question 49

Granzyme 1) 2)

Answer 49

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

Question 50

What is serglycin?

Answer 50

Forms a complex with perforin and granzymes

Question 51

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

Answer 51

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

Question 52

What forms a complex with granzyme and perforin?

Answer 52

Serglycin

Question 53

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

Answer 53

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

Question 54

What plays a major role in eliminating unwanted T cells?

Answer 54

Death via the Fas/FasL pathway

Question 55

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

Answer 55

Autoimmune lymphoproliferative disease

Question 56

What causes autoimmune lymphoproliferative disease?

Answer 56

Mutations in the Fas/FasL pathway

Question 57

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

Answer 57

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

Question 58

What can activate Th IFNg release?

Answer 58

Only professional APCs