T Cell Activation After Thymus Flashcards

1
Q

Naive T cells from thymus (single positive) recirculate where

A

Secondary lymphoid tissues LN and spleen

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2
Q

How do naive T cells enter lymph node

A

HEV

High endothelial venues

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3
Q

What does contact with ag cause for naive T cells

A

Proliferation and differentiation into effector T cells (cytotoxic CD8 or Th cells CD4)

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4
Q

What cells are in T cell area of LN for T cell activation and differentiation

A

APC with mhcs like macrophages, dendrites ,

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5
Q

What happens to T cells which don’t get activated by ag on apc

A

Leave the LN via the cortical suinuses for recirculation. They are recycled or die

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6
Q

What happens to activated ag T cells

A

They get blocked from leaving the LN until proliferated via clonal expansion and differentiation into effector cells

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7
Q

What helps localise T cells when they become effectors

A

Chemokines because they have chemokine receptors on surface

So leave the LN and go to target sites

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8
Q

What are CAMs

A

Cell adhesion molecules which help T cells attach to other cells/tissues

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9
Q

Give 3 things cams needed for T cell attachment

A

To the HEV to go to lymph node

To APC helping to stay attached for ag signal

To target cells

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10
Q

Give an example of a CAM which helps T cell interaction with APC

A

Icam 1 present on APC with MHC II on surface

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11
Q

Initially, for activation T cells interact with apc via low affinity ICAM1. What does this bind to on T cells

A

LFA 1

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12
Q

What does cd3 signalling when ag on MHC binds T cell do

A

Changes LFA shape so it has HIGH affinity for ICAM on apc. Causes T cell to stay longer

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13
Q

As well as the icam lfa intersction. What helps T cells attachment/interaction with MHC antigen

A

CD4 which attaches to the tcr in MHC II signalling

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14
Q

T cells need 3 signals for activation whats the first one

A

MHC signal via cd3 zeta phosphorylation of ITAMs which then causes change in LFA affinity for icam

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15
Q

What do apc have on their surface for signal 2

A

Co stimulatory molecules like B7 1 and 2

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16
Q

What do co stimulatory molecules on APC bind to on T cells for signal 2

A

B7 binds to cd28 on naive T cells

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17
Q

In signal 3, what do apc release which allows T cell activation (expansion and differentiation)

A

Cytokines determine type of effector cell

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18
Q

When T cells get activated. What do they upregulate as a negative feedback system

A

ICOS (binds to ICOSL on apc)

And

CTLA 4

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19
Q

How does CTLA4 stop T cell expansion in Negative feedback

A

CTLA 4 bind to B7 co stimulatory molecules on apc blocking cd28 and signal 2 of T cell activation.

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20
Q

Which autoimmune disease is caused by mutation in ctla4

A

Diabetes. T cell can’t stop the signal 2 from B7 binding to cd28 = over reactive

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21
Q

What does apc activation occur so that they can go on to stimulate T cell expansion

A

PRR like TLR

Detect pathogens by Pamps like lps

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22
Q

What is prr detection of pamps called

A

Danger signal

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23
Q

What do apc upregulste after danger signal to ensure signal 2 of T cell activation

A

B7 co stimulatory factor and MHC

24
Q

What do cytokines released by apc in signal 3 do

A

Turn on transcription factors which cause T cells to further release them for auto proliferation

25
Q

Which cytokines released by apc in signal 3 turn on a TF for th1 cells

A

Il 12 and ifn y

Activate th1

Th1 then produce il 2 and ifn y for own proliferation and other purposes

26
Q

What cytokine is released by apc which is the released by the activated th2 cell

A

Il4 activated th2 differentiation then th2 further releases il4 due to a TF turn on

27
Q

Which cytokine released by apc causes stimulation of tfh cells

A

Il 6

28
Q

Do cytokines in signal 3 only determine CD4 cells eg th1,tfh and th2

A

Yes as CD8 don’t have others except cytotoxic T cells

29
Q

What are the 3 main apc with MHC II for CD4 activation

A

Macrophages dendrites and B cells

30
Q

How do dendritic cells uptake exogenous ag

A

Macropinocytosis and phagocytosis

31
Q

Which type of dendritic cell is the most potent apc for T cell activation

A

Myeloid conventional dendritic cell (Dc 2 and 3)

6 types though

32
Q

Where do immature myeloid conventional dc wait for ag uptake

A

Skin/epithelial tissues

33
Q

When myeloid conventional dc get a danger signal what do they do

A

Start to express B7 co stimulatory molecules for T cell signal 2 and they move to lymph node to present ag on MHC II

34
Q

Which dendritic cells are for viral infections

A

Plasmacytoid dendritic cells

35
Q

When do myeloid conventional dc 2 and 3 stop up taking ag

A

When the danger signal received, they’ve uptaken a ag and moved to lymph node with a B7 on surface

36
Q

Can dendrites be both mhc

A

Yes mhc 1 and 2

37
Q

Do myeloid conventional dc produce cam like icam 1 for signal 1 of T cell activation

A

Yes

38
Q

What directs MC dendritic cells to lymph node

A

Chemokines attaching to their chemokine receptors

39
Q

What is cross presentation via DC 1

A

Where they present exogenous ag on class I instead of class 2 mhc

This allows CD8 activation which can now kill infected cells which aren’t presenting their ag on MHC II and have no co stimulatory molecules for T cell activation

40
Q

How do macrophages internalise ag

A

Same as dc

Macropinocytosis and phagocytosis

(After a danger signal received by pamps and prr)

41
Q

After internalisation of ag by macrophages what happens

A

They upregulste B7 and move to LN for T cell activation
They also release cytokines like Ifn y which help CD4 differentiate into th1 for example

They do this for their OWN benefit as T cell release of cytokines activates macrophages

42
Q

Do B cells have good or bad phagocytosis

A

Bad

43
Q

How are SPECIFIC ag internalised into B cells for bcr presentation

A

receptor mediated endocytosis

44
Q

What upregulates B7 in B cells for co stimulation signal 2 of t cells

A

Bcr binding of specific antigens

45
Q

Why do B cells activate T cells via this

A

Because they need T cells to in turn activate them

46
Q

What has it been shown recently bcr can do

A

Extract ag from other cells to increase their own activation as they put it on their class II for t activation

47
Q

Which cytokine is a potent T cell growth factor

A

Il 2 (induced T cell cell cycle)

48
Q

How do IL 2 receptors on naive and activated T cells differ

A

Naive the receptors for il 2 are low affinity. Naive can’t proliferate fast

When T cells become activated fully via the 3 signals they gain a high affinity il 2 receptor which binds il 2 causing cells like th1 to proliferate fast

49
Q

Which drugs can target il 2

A

Immunosuppressive drugs to stop T cell proliferation

50
Q

Effector T cells enter tissues how

A

Leaky endothelium

51
Q

Do cams change in effector T cells

A

Yes. They now need to stick to target tissues

52
Q

What is no longer needed when effector T cells become effectors

A

B7 co stimulatory molecules on apc

53
Q

What do CD8 kill

A

Infected cells presenting peptide on MHC I and that have co stimulatory molecules

Or

Infected cell once been activated by cross presenting dc1 via MHC I

(For infected cells without costimulatory molecule)

54
Q

What do CD8 cells need for activation to kill

A

Many co stimulation molecules on apc or help from CD4 cells

55
Q

What is zap

A

Zeta associated protein which is a tyrosine kinase causing signalling through cd3 in signal 1