8) T cell differentiation and function

What is different feature of TCR to BCR?

-Monovalent

-No antibody: membrane bound only

-No somatic hypermutation

-No effector function just recognition function: no Fc portion

TCR initial structure formation

Similar to antibodies: somatic recombination

What is different about the somatic recombination of TCR to BCR?

1) Beta chain recombines first and relies on a surrogate alpha chain

2) Initially double negative

3) Alpha chain recombination occurs

4)Surrogate alpha chain replaced

4)Once beta chain has formed then CD4 and CD8 can be expressed

What happens at the cortex of the thymus?

Positive selection of T-cells by cortical epithelial cells in thymus.

What happens at the medulla of thymus?

Negative selection of T-cells by dendritic cells, macrophages and other cells in the thymus.

What does an activa

What is the first step of TCR signalling?

1. TCR complex ad co-receptrs are clustered upon antigen recognition 

What is the second step of TCR signalling?

2. Lck kinase phosphorylates tyrosines in ITAMs of CD3 and zeta chains. ZAP70 binds to phosphotyrosines.

What is the third step of TCR signalling?

3, ZAP70 phosphoryates LAT (sIgnallasome)

Signallasome

forms a hub for activation of further downstream signalling components

What is the fourth step of TCR signalling?

Phosphorylated LAT recruits Grb2 and PLC-gamma-1

What is the fifth step of TCR signalling?

This leads to downstream activation of effector molecules

What is the outcome of TCR signalling?

Activation of T-cell triggers conversion of T-cell from a naive, metabolically quiescent cell to a highly proliferative and activated cell that is metabolically active.

What is the signal for CD8 T-cells to expand ad proliferate?

IL-2

What are the 5 main subsets of naive T-cells?

1.Th1

2.Th2

3.Th17

4.Tfh

5.Treg

Th1

Th2

Th17

Tfh

Treg

What cytokines induce Th1?

IFN-gamma, IL-12

What cytokines induce Th2?

IL-4

What cytokines induce Th17?

TGF-beta, IL-6, IL-23

What cytokines induce Tfh?

What cytokines induce Th2?

What does Th1 secrete?

IFN-gamma

What does Th1 secrete?

IL-4,IL-5,IL-13

What does Th17 secrete?

IL-17

What does Tfh secrete?

IL-21

What does Treg secrete?

TGF-beta, IL-10

What is the effect of IFN-gamma released by Th1?

Activates STAT1

What is the effect of IL-12 released by Th1?

STAT4

What is the effect of STAT1 and 4?

Activation of master transcription factor T-bet

What does T-bet induce?

Th1

What is the effect of IL-4 released by Th2?

Activation of STAT6

What does STAT6 activate?

GATA-3

What does GATA-3 induce?

Th2

What is the effect of IL-6 released by Th17 and Tfha?

STAT3 activation

What does STAT3 do?

ROR-gamma-T, Bcl-6

What does ROR-gamma-T induce?

Th17

What does Bcl-6 induce?

Tfh

What does IL-23 do?

Activate STAT3

What does IL-2 activate?

STAT5

What does STAT5 activate?

Master regulator FoxP3

What does FoxP3 induce?

Treg

What inhibits Th1?

IL-4, TGF-beta (by Treg)

What inhibits Th2?

IFN-gamma, TGF-beta (by Treg)

What inhibits Th17?

IL-4, IFN-gamma 

What does Tfh secrete to license B-cell activation?

IL-4,IL-10

What is the ILC for Th1?

ILC1

What is the ILC for Th2?

ILC2

What is the ILC for Th17?

ILC3

What is the ILC for Th22?

ILC3

What is the ILC of killer T cells?

NK cells

What is the type 1 ILC response?

What is the type 2 ILC response?

What is the type 3 ILC response?