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Infection, immunity and repair > T cell polarisation and biomarkers > Flashcards

T cell polarisation and biomarkers Flashcards

1
Q

What cells give rise to most cells in the IS?

A

Progenitors

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2
Q

What do lymphocytes look like?

A

Small cells with relatively large nuclei

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3
Q

Key features of T cells

A

Develop in the thymus

Bear an antigen specific receptor - TCR

Interact with APCs to see antigen

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4
Q

What is a common feature of all T cells?

A

All bear an antigen specific receptor TCR

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5
Q

What happens to T cells upon interactions with APCs bearing antigens?

A

The T cells proliferate if they recognise the antigen

Make large population of clones

Release cytokines

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6
Q

What is a thymocyte?

A

An early T cell that is developing in the thymus

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7
Q

What is the major feature of naive alpha beta T cells when they leave the thymus?

A

They comit to expressing only either CD4 or CD8 proteins on their surface

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8
Q

What is the difference between alpha beta T cells and gamma delta T cells?

A

Alpha beta T cells express CD4 or CD8 proteins on their surface

Gamma delta T cells don’t express either CD4/CD8

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9
Q

What class of MHC molecules do CD 4 T cells bind to?

A

MHC II

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10
Q

How do CD 4 T cells recognise antigens?

A

Presented on MHC II on APCs

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11
Q

What is the role of CD 4 T cells?

A

Make cytokines - provide help to other immune cells

Instruct and orchestrate the immune response

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12
Q

What is the common name for CD 4 T cells?

A

T helper cells

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13
Q

What class of MHC proteins do CD 8 T cells bind to?

A

MHC I

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14
Q

How do CD 8 T cells recognise antigens?

A

Bind to MHC I on infected cells

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15
Q

On which cells are MHC I molecules found?

A

On all somatic nucleated cells of vertebrates

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16
Q

What is the role of CD 8 T cells?

A

Kill target cells - virally infected and tumour cells

Make cytokines

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17
Q

What is the common name for CD 8 T cells?

A

Cytotoxic T cells

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18
Q

What is CD 3?

A

Name given to a collection of molecules that all T cells express on their surface

Coreceptors needed for T cells to perform normal function

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19
Q

On which T cells are TCRs expressed?

A

On all T cells

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20
Q

What are the two regions of the TCR?

A

Constant region - doesn’t vary much

Variable region - unique to each T cell

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21
Q

What does the high variability of the TCR variable region allow T cells to do?

A

Allows them to recognise different MHC combinations

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22
Q

What is the source of the large repertoire of T cells?

A

Large variety TCRs produced by the body

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23
Q

The functional population of T cells is as large as the potential repertoire

TRUE or FALSE

A

FALSE

The functional population of T cells is not as large as the potential repertoire

Number of different TCRs made by the thymus is bigger than the total lymphocyte count

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24
Q

What do CD 4 and CD 8 molecules bind to?

A

Non-polymorphic residues on MHC I or II

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25
Q

What does thymic selection do to the bond between MHC and TCR?

A

Strengthens it

The TCRs with the highest affinity are selected

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26
Q

Why do we need the CD 4/8 to bind to MHC molecules?

A

TCR has a relatively week biochemical binding

If the only interaction between APCs and T cells was between TCRs and MHC the cells would come apart before anything could happen

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27
Q

What does binding between TCR and MHC do to intracellular environment of the T cell?

A

Recruits signaling molecules to the immunological patch

Drives cytoskeletal movements in the T cells

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28
Q

CD 4 cells can be subdivided depending on the cytokines produced

TRUE or FALSE

A

TRUE

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29
Q

What are the different sub types of CD 4 T cells?

A

Th1

Th2

Th17

Regulatory T cells

T follicular helper cells

30
Q

Which cytokines do Th1 cells release?

A

Gamma interferon and IL-2

31
Q

Which cytokines do Th2 cells release?

A

IL-4, IL-5, IL-6, IL-10 and IL-13

Strongly associated to immunity to worms, parasites and helminths

32
Q

Which cytokines do Th17 cells release?

A

IL - 17

Pro-inflammatory

33
Q

What is the function of Th2 cells?

A

Immunity to worms, parasites and helminths

34
Q

What is the function of Th17 cells?

A

Pro-inflammatory cells

35
Q

What is the function of regulatory T cells?

A

Main funciton is to dampen down the immune system

36
Q

What is the function of T follicular helper cells?

A

Critical to drive the cells inside the lymoh nodes

37
Q

Can polarisation be changed in a T cell?

A

Yes

38
Q

Who discovered the Th1/ Th2 division?

A

Mossman and Coffman in 1986

39
Q

Mossman and Coffman belived the Th1 and Th2 were completely separate developmental pathways

Can’t switch between the two polarisations

TRUE or FALSE

A

TRUE

This is a false belief though - Th1 and Th2 polarisation is interchangeable

40
Q

What is the role of Th1 cells?

A

Protect against viruses, TB and intracellular parasites

41
Q

What do the cytokines released by Th1 cells signal through?

A

STAT 4

42
Q

What is the main transcription factor in Th1 cells that drive its formation?

A

T bet

43
Q

What is the role of Th2 cells?

A

Protect against extracellular pathogens

44
Q

What do the cytokines released by Th2 cells signal through?

A

STAT 6

45
Q

What is the main transcription factor that drives Th2 molecule formation?

A

GATA-3

46
Q

Cytokines released by Th1/2 inhibit each other

TRUE or FALSE

A

TRUE

Th1 and Th2 cells cross-regulate each other

47
Q

How do you differentiate between Th1 and Th2 cells?

A

By the chemokine receptors they express on CSM

48
Q

What chemokine receptor is expressed on Th1 cells?

A

CXCR3

49
Q

What chemokine receptor is expressed on Th2 cells?

A

CCR3

50
Q

Summary of characteristics of Th1 cells

A

Cytokines: IL-2 and gamma interferon

Cytokines signal through STAT4

Chemokine receptor = CXCR3

Transcription factor T bet important for formation of molecule

51
Q

Summary of characterisitics of Th2 cells

A

Cytokines: IL-4, IL-5, IL-6, IL-10, IL-13

Cytokines signal through STAT6

Chemokine receptor = CCR3

Transcription factor GATA-3 important for formation of molecule

52
Q

How is MS linked to Th cells?

A

Mice with no STAT4 or Tbet were protected against MS

Therefore Th1 cells important in the pathogenesis of the disease

Mice with gamma interferon should have been protected too - got worsening disease

53
Q

How is arthritis linked to Th cells?

A

Drugs that block Th17 are used to treat arthritis

Th17 are therefore important in the pathogenesis of the disease

54
Q

What is meant by the term plasticity in context to Th cells?

A

T cells in their specific polarisation/ phenotype are plastic

55
Q

What is an example of Th cells showing plasticity?

A

Th17 cells removed from synovial fluid of juvenile arthritis sufferers

In high concentration in these patients

Placing these cells in a petri dish makes them switch

56
Q

What is the biomarker for Th 17 cells?

A

CCR 6

57
Q

How can you tell Th cells have switched polarisation?

A

Th17 cells that switched to Th1 still expressed markers of Th17

Express both IL-17 and IFN = hybrid

58
Q

Why is it difficult for Th1 cells to switch to Th17?

A

Energy difference

Th17 is less stable

59
Q

Are T regulatory cells strongly polarised?

A

Yes

60
Q

What is an important molecule for Tregs?

A

CTLA-4

Mice lacking = huge lymph nodes - too many effector T cells produced

61
Q

What is IPEX?

A

X-linked genetic abnormality

Can’t make Tregs - require bone marrow transplant

62
Q

What is the biomarker for T reg cells?

A

CD25 receptor

63
Q

What gene codes for CD25?

A

IL-2 RA

64
Q

What is the master transcription factor of Treg cells?

A

Foxp3

65
Q

How do Tregs inhibit the function of effector T cells?

A

IL-2 is an important cytokine for effector cells

Tregs outcompete effector cells for this cytokine

66
Q

Which cells produce IL-2?

A

Not Tregs

Other cells at wound site

67
Q

What can Th17 cells convert to apart from Th1 cells?

A

Treg cells

68
Q

Why is it relatively easy for Treg cells to change polarisation into Th17 cells and viseversa?

A

Both express the same homing receptors - CCR4 and CCR6

Develop under the production of the same cytokine - TGFb

69
Q

What does conversion between these two phenotypes depend on?

A

Cytokines

Environment

Infection

70
Q

What is the role of Th17?

A

Pro-inflammatory

71
Q

What is CD161+?

A

A hybrid of Treg and Th17 cells

Express Th17 (CD161) molecules and Treg (CD4, Foxp3 and CD25) molecules

72
Q

What on Treg cells binds to IL-2?

A

CD 25

Infection, immunity and repair (52 decks)

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