T Cell Activation After Thymus

Question 1

Naive T cells from thymus (single positive) recirculate where

Answer 1

Secondary lymphoid tissues LN and spleen

Question 2

How do naive T cells enter lymph node

Answer 2

HEV

High endothelial venues

Question 3

What does contact with ag cause for naive T cells

Answer 3

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

Question 4

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

Answer 4

APC with mhcs like macrophages, dendrites ,

Question 5

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

Answer 5

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

Question 6

What happens to activated ag T cells

Answer 6

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

Question 7

What helps localise T cells when they become effectors

Answer 7

Chemokines because they have chemokine receptors on surface

So leave the LN and go to target sites

Question 8

What are CAMs

Answer 8

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

Question 9

Give 3 things cams needed for T cell attachment

Answer 9

To the HEV to go to lymph node

To APC helping to stay attached for ag signal

To target cells

Question 10

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

Answer 10

Icam 1 present on APC with MHC II on surface

Question 11

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

Answer 11

LFA 1

Question 12

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

Answer 12

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

Question 13

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

Answer 13

CD4 which attaches to the tcr in MHC II signalling

Question 14

T cells need 3 signals for activation whats the first one

Answer 14

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

Question 15

What do apc have on their surface for signal 2

Answer 15

Co stimulatory molecules like B7 1 and 2

Question 16

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

Answer 16

B7 binds to cd28 on naive T cells

Question 17

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

Answer 17

Cytokines determine type of effector cell

Question 18

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

Answer 18

ICOS (binds to ICOSL on apc)

And

CTLA 4

Question 19

How does CTLA4 stop T cell expansion in Negative feedback

Answer 19

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

Question 20

Which autoimmune disease is caused by mutation in ctla4

Answer 20

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

Question 21

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

Answer 21

PRR like TLR

Detect pathogens by Pamps like lps

Question 22

What is prr detection of pamps called

Answer 22

Danger signal

Question 23

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

Answer 23

B7 co stimulatory factor and MHC

Question 24

What do cytokines released by apc in signal 3 do

Answer 24

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

Question 25

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

Answer 25

Il 12 and ifn y Activate th1 Th1 then produce il 2 and ifn y for own proliferation and other purposes

Question 26

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

Answer 26

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

Question 27

Which cytokine released by apc causes stimulation of tfh cells

Answer 27

Il 6

Question 28

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

Answer 28

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

Question 29

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

Answer 29

Macrophages dendrites and B cells

Question 30

How do dendritic cells uptake exogenous ag

Answer 30

Macropinocytosis and phagocytosis

Question 31

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

Answer 31

Myeloid conventional dendritic cell (Dc 2 and 3) 6 types though

Question 32

Where do immature myeloid conventional dc wait for ag uptake

Answer 32

Skin/epithelial tissues

Question 33

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

Answer 33

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

Question 34

Which dendritic cells are for viral infections

Answer 34

Plasmacytoid dendritic cells

Question 35

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

Answer 35

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

Question 36

Can dendrites be both mhc

Answer 36

Yes mhc 1 and 2

Question 37

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

Answer 37

Yes

Question 38

What directs MC dendritic cells to lymph node

Answer 38

Chemokines attaching to their chemokine receptors

Question 39

What is cross presentation via DC 1

Answer 39

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

Question 40

How do macrophages internalise ag

Answer 40

Same as dc Macropinocytosis and phagocytosis (After a danger signal received by pamps and prr)

Question 41

After internalisation of ag by macrophages what happens

Answer 41

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

Question 42

Do B cells have good or bad phagocytosis

Answer 42

Bad

Question 43

How are SPECIFIC ag internalised into B cells for bcr presentation

Answer 43

receptor mediated endocytosis

Question 44

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

Answer 44

Bcr binding of specific antigens

Question 45

Why do B cells activate T cells via this

Answer 45

Because they need T cells to in turn activate them

Question 46

What has it been shown recently bcr can do

Answer 46

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

Question 47

Which cytokine is a potent T cell growth factor

Answer 47

Il 2 (induced T cell cell cycle)

Question 48

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

Answer 48

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

Question 49

Which drugs can target il 2

Answer 49

Immunosuppressive drugs to stop T cell proliferation

Question 50

Effector T cells enter tissues how

Answer 50

Leaky endothelium

Question 51

Do cams change in effector T cells

Answer 51

Yes. They now need to stick to target tissues

Question 52

What is no longer needed when effector T cells become effectors

Answer 52

B7 co stimulatory molecules on apc

Question 53

What do CD8 kill

Answer 53

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)

Question 54

What do CD8 cells need for activation to kill

Answer 54

Many co stimulation molecules on apc or help from CD4 cells

Question 55

What is zap

Answer 55

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