T cell polarisation and biomarkers Flashcards

(72 cards)

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
What does thymic selection do to the bond between MHC and TCR?
Strengthens it The TCRs with the highest affinity are selected
26
Why do we need the CD 4/8 to bind to MHC molecules?
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
27
What does binding between TCR and MHC do to intracellular environment of the T cell?
Recruits signaling molecules to the immunological patch Drives cytoskeletal movements in the T cells
28
CD 4 cells can be subdivided depending on the cytokines produced TRUE or FALSE
TRUE
29
What are the different sub types of CD 4 T cells?
Th1 Th2 Th17 Regulatory T cells T follicular helper cells
30
Which cytokines do Th1 cells release?
Gamma interferon and IL-2
31
Which cytokines do Th2 cells release?
IL-4, IL-5, IL-6, IL-10 and IL-13 Strongly associated to immunity to worms, parasites and helminths
32
Which cytokines do Th17 cells release?
IL - 17 Pro-inflammatory
33
What is the function of Th2 cells?
Immunity to worms, parasites and helminths
34
What is the function of Th17 cells?
Pro-inflammatory cells
35
What is the function of regulatory T cells?
Main funciton is to dampen down the immune system
36
What is the function of T follicular helper cells?
Critical to drive the cells inside the lymoh nodes
37
Can polarisation be changed in a T cell?
Yes
38
Who discovered the Th1/ Th2 division?
Mossman and Coffman in 1986
39
Mossman and Coffman belived the Th1 and Th2 were completely separate developmental pathways Can't switch between the two polarisations TRUE or FALSE
TRUE This is a false belief though - Th1 and Th2 polarisation is interchangeable
40
What is the role of Th1 cells?
Protect against viruses, TB and intracellular parasites
41
What do the cytokines released by Th1 cells signal through?
STAT 4
42
What is the main transcription factor in Th1 cells that drive its formation?
T bet
43
What is the role of Th2 cells?
Protect against extracellular pathogens
44
What do the cytokines released by Th2 cells signal through?
STAT 6
45
What is the main transcription factor that drives Th2 molecule formation?
GATA-3
46
Cytokines released by Th1/2 inhibit each other TRUE or FALSE
TRUE Th1 and Th2 cells cross-regulate each other
47
How do you differentiate between Th1 and Th2 cells?
By the chemokine receptors they express on CSM
48
What chemokine receptor is expressed on Th1 cells?
CXCR3
49
What chemokine receptor is expressed on Th2 cells?
CCR3
50
Summary of characteristics of Th1 cells
Cytokines: IL-2 and gamma interferon Cytokines signal through STAT4 Chemokine receptor = CXCR3 Transcription factor T bet important for formation of molecule
51
Summary of characterisitics of Th2 cells
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
How is MS linked to Th cells?
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
How is arthritis linked to Th cells?
Drugs that block Th17 are used to treat arthritis Th17 are therefore important in the pathogenesis of the disease
54
What is meant by the term plasticity in context to Th cells?
T cells in their specific polarisation/ phenotype are plastic
55
What is an example of Th cells showing plasticity?
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
What is the biomarker for Th 17 cells?
CCR 6
57
How can you tell Th cells have switched polarisation?
Th17 cells that switched to Th1 still expressed markers of Th17 Express both IL-17 and IFN = hybrid
58
Why is it difficult for Th1 cells to switch to Th17?
Energy difference Th17 is less stable
59
Are T regulatory cells strongly polarised?
Yes
60
What is an important molecule for Tregs?
CTLA-4 Mice lacking = huge lymph nodes - too many effector T cells produced
61
What is IPEX?
X-linked genetic abnormality Can't make Tregs - require bone marrow transplant
62
What is the biomarker for T reg cells?
CD25 receptor
63
What gene codes for CD25?
IL-2 RA
64
What is the master transcription factor of Treg cells?
Foxp3
65
How do Tregs inhibit the function of effector T cells?
IL-2 is an important cytokine for effector cells Tregs outcompete effector cells for this cytokine
66
Which cells produce IL-2?
Not Tregs Other cells at wound site
67
What can Th17 cells convert to apart from Th1 cells?
Treg cells
68
Why is it relatively easy for Treg cells to change polarisation into Th17 cells and viseversa?
Both express the same homing receptors - CCR4 and CCR6 Develop under the production of the same cytokine - TGFb
69
What does conversion between these two phenotypes depend on?
Cytokines Environment Infection
70
What is the role of Th17?
Pro-inflammatory
71
What is CD161+?
A hybrid of Treg and Th17 cells Express Th17 (CD161) molecules and Treg (CD4, Foxp3 and CD25) molecules
72
What on Treg cells binds to IL-2?
CD 25