17 - T cells I : Module intro/overview & signal 3: T cell differentiation

Question 1

where is signal 3

Answer 1

in lymph node

Question 2

t cell exert their function is also called … immunity

Answer 2

cell-mediated immunity

Question 3

once infection cleared, there are…

Answer 3

regulation& memory

Question 4

3 signals to activate T cells

Answer 4

• Signal 1: pMHC:TCR
• Signal 2: B7:CD28
• Signal 3: Cytokines
  -Lead to differentiation of T cell

Question 5

main job of CD8+ T cell once becomes effector T cells

Answer 5

directly kill infected/targeted cells

Question 6

TFH (Follicular Helper T cell), what do they do?

Answer 6

• TFH – helps B cells get activated

Question 7

Different roles of different effector T cells (examples)

Answer 7

• Some help activate B cells
• Some help activate macrophages
• Some kill infected cell directly

Question 8

for T cells to carry out its function, it has to…, what is the road they take?

Answer 8

leave the lymph node

Efferent lymphatic vessels -> thoracic duct -> blood stream -> site of infection

Question 9

once T cell is at the site of infection…it exerts…

Answer 9

Cell-Mediated immunity

example: Th1 cytokines promote Tc Killing & macrophage ROS killing

Question 10

once T cell have exerted their function, and infection has been hopefully cleared… there is…

Answer 10

Downregulation of T cell activity & immunological Memory

• Some are downregulated
• Some become memory T cells

Question 11

why is Signal 3 important

Answer 11

for T cell differentiation

Question 12

waht is signal 3?

Answer 12

cytokines directing T-cell differentiation into distinct effector cell types

Question 13

all 3 signals ( TCR signaling, costimulatory interaction & cytokine signaling) lead to

Answer 13

intracellular signal, leading to change in T cell:
o Activation
o Proliferation
o Survival
o Differentiation

Question 14

Activated T cells will ….

Answer 14

o Proliferate
o Differentiate - CD4+, CD8+ T cells & Regulatory T cells

Question 15

differentiation of CD4+ T helper cells

Answer 15

• From TH0 to (Depending on cytokine)
  TH1, TH2, TFH, TH17, Others

Question 16

differentiation of CD8+ T cells

Answer 16

cytotoxic T lymphocyte (CTL)

Question 17

what is Effector T cells

Answer 17

resulting differentiated T cells from activated T cells
-have an effect on immune response

Question 18

effector Cells classified depending on

Answer 18

o Transcription factors they express
o Profile of cytokines the make
o Main function in adaptive immunity

Question 19

Once activated - an effector T cell doesn’t require … to act

Answer 19

co-stimulation (signal 2)

Question 20

Different effector cells have…

Answer 20

different functions

Question 21

5 subtypes of CD4+ T cells

Answer 21

o TH1
o TH2
o TH17
o TFH
o Treg

Question 22

Effector T cells can impact

Answer 22

functionality of other immune cells

Question 23

Different cytokines secreted by effector T cells

Answer 23

have different function

Question 24

Differentiation of T helper cell subsets – regulated by

Answer 24

signal 3 cytokines (polarizing cytokines)

Question 25

different pathogens -->

Answer 25

polarizing cytokine --> different functions

Question 26

role of polarizing cytokines

Answer 26

guiding a T cell toward one of several different effector fates

Question 27

APCs bind ... via ..., induce....

Answer 27

PAMPS via PRRs Induce cytokine secretion

Question 28

Different PRRs engaged - via...

Answer 28

different PAMPs = different cytokines produced examples: o Viruses stimulate IL-12 to induce TH1 subset o Worms/helminths stimulate IL-4 to induce TH2 subset

Question 29

Fate-specifying cytokines (polarizing cytokines) --> ....

Answer 29

diffeent T cell subset (Effector T cells)--> effector cytokines

Question 30

How does signal 3 exert its effect?

Answer 30

* Cytokines bind their receptor & induce intracellular signaling--> STAT proteins phosphorylated (Act as TF) ----> Go inside nucleus --> bind to specific promoters on specific genes & lead to their trancription & translation * Key gene being transcribed = alsoTF (Master Transcriptional Regulator)--> can bind response elements on promoter regions on genes coding for specific effector cytokines -->determines activity of activated, differentiated T cell subtype

Question 31

example for type (1&2) Type of responses Master transcription regulators Effector cytokines

Answer 31

o Type 1: intracellular pathogens o Type 2: extracellular parasites o Type 1 response: T-Bet o Type 2 response: GATA-3 o From TH1 -IFN-y o From TH2 IL-4, IL-5, IL-13

Question 32

each naive CD4+ T cell must...

Answer 32

express of STAT proteins which one gets phosphorytlated makes the difference

Question 33

pathogen type/PAMP determine

Answer 33

Type of cytokine produced by APC leading to polarizing cytokines

Question 34

Cytokine signals via

Answer 34

STAT proteins, depeding on waht gets phosphorylated, Induce expression of new TF – master transcriptional regulators Promote expression of genes encoding for specific cytokines – effector cytokines – help exert function

Question 35

signal 3 result:

Answer 35

Result = differentiated effector T cell with distinct function