module 05 section 03 (cytokines in T-cell differentiation)

Question 1

recall: cytokines produced in response to pathogens by innate immune cells play a role in the subsequent adaptive response via the decision to differente T-cells into:
(Th1 or Th2 cells)

Answer 1

Th1 cells

Question 2

recall: what are Th1 cells?

Answer 2

subset of helper T-cells that induce cell-mediated functions such as delayed-type hypersensitivity and activation of T-cells

Question 3

recall: what are Th2 cells?

Answer 3

subset of helper T-cells that induce activation of B-cells and stimulate eosinophils

Question 4

explain what happens when the APC-MHC complex interacts with the CD4 co-receptor on the helper T-cell

Answer 4

the helper T-cells signals in an autocrine fashion by secreting IL-2, which induces cell proliferation, creating activated T-cells (which secrete distinct sets of cytokines)

Question 5

when can T-cells differentiate into Th1 or Th2?

Answer 5

after they are activated

Question 6

explain the induction of Th1 cells (how are they produced)

Answer 6

activated APCs secrete IL-12 which promotes T-cell differentation to Th1+ cells through the activation of STAT4

Question 7

what is STAT4?

Answer 7

• transcription factor required for the development of Th1 cells from naive CD4+ T-cells
• I.e. signal transducer and activator of transcription 4

Question 8

explain the induction of Th2 cells (how are they produced)

Answer 8

basophils and mast cells secrete IL-4 to promote T-cell differentiation to Th2+ cells through the activation of STAT6

Question 9

what is STAT6?

Answer 9

• protein that plays a central role in exerting IL-4 mediated responses
• signal transducer and activator of transcription 6

Question 10

recap: the activation of what promotes commitment to either Th1 or Th2 lineage?

Answer 10

activation of STAT

Question 11

what is the main pathway associated with cytokine signalling inside of the cell that results in T-cell commitment?

Answer 11

the JAK-STAT pathway

Question 12

define JAK

Answer 12

JAnus Kinase: family of intracellular, non receptor tyrosine kinases that transduce cytokine-mediated signals via the JAK-STAT pathway

Question 13

define STAT

Answer 13

signal transducers and activators of transcription: family of intracellular transcription factors that mediate many aspects of cellular proliferation and differentiation

Question 14

explain the 6 steps of the JAK-STAT pathway

Answer 14

(1) cytokine binds to cytokine receptor causing it to dimerize
(2) activation of JAK family tyrosine kinases resulting in phosphorylation of the receptor
(3) tyrosine phosporylation os STAT by JAK kinase
(4) dimerization of STAT
(5) translocation of STAT into the nucleus and binding to DNA
(6) specific gene transcription commiting the T-cell to Th1 or Th2 lineage

Question 15

newly differentiated T-cells (th1 or Th2) can secrete cytokines that either:

Answer 15

-inhibit proliferation of the other subset
OR
-enhance the proliferation of its own subset through pos feedback
-called cross regulation

Question 16

how is the population of specific subsets of T-cells during infection controlled?

Answer 16

cross-regulation (described in previous card)

Question 17

IFN-y, IL-2 and TNF-a have positive feedback effects on:

Answer 17

the Th1 cell and the macrophage or dendritic cell

Question 18

IFN-y, IL-2 and TNF-a have negative feedback effects on:

Answer 18

the Th2 cell

Question 19

IL-4, IL-5, IL-10 and IL-13 have positive feedback effects on:

Answer 19

the Th2 cell

Question 20

IL-4, IL-5, IL-10 and IL-13 have negative feedback effects on

Answer 20

the Th1 cell

Question 21

the differentiation of naive CD4+ cells into Th1 or Th2 determines:

Answer 21

the type of immune response

Question 22

how can Th1 and Th2 cells be distinguised most clearly?

Answer 22

by the cytokines they produce and their resulting effector functions

Question 23

what do Th1 cells secrete and what are the effector functions?

Answer 23

• secrete IFN-y (promotes further Th1 differentation and inhibits the proliferation of Th2 cells)
• effector functions: play role in the cell-mediated immune response

Question 24

what do Th2 cells secrete and what are the effector functions?

Answer 24

• secrete IL-4 and IL-5 and a little IL-10 (promotes Th2 differentation and inhibits activation of Th1 cells)
• effector functions: play role in the humoral immune response

Question 25

recap: do the following statements apply to Th1 cells, Th2 cells or both ?

(1) activated by IL-12 and STAT4
(2) activated by IL-4 and STAT6
(3) involved in humoral immunity
(4) involved in cell-mediated immunity
(5) activation is inhibited by IL-4, IL-5 and IL-10
(6) proliferation is inhibited by IFN-y
(7) associated with the JAK-STAT signalling pathway

Answer 25

(1) Th1
(2) Th2
(3) Th2
(4) Th1
(5) Th1
(6) Th2
(7) Both