1.08 - Effector & Memory T-Cells

Question 1

Describe DC and T cell circulation

Answer 1

DC cells exposed to the antigen at the infection site will then travel to local draining lymph nodes.
Here it will present the antigen on MHC Class II to naive T cell. This will activate the naive T cell to forming effector and memory T cells
Effectors T cells will leave the lymph node via the efferent duct –> travel to the site of infection, and mediate its effects there

Question 2

What are the characteristic of immunological memory?

Answer 2

Quantitative (quantitatively different to naive cell population)
Qualitative: readily converted to effects
- Memory cells behave differently to naive lymphocytes
Altered recirculation
Long-lived

Question 3

Describe the signals in clonal expansion of T-Cells

Answer 3

Two distinct signals required for T cell activation

IL-2 is particularly important for T cell activation

Question 4

Describe the changes in T-Cells that allow them to leave the lymph node

Answer 4

Naive T cells locoed in lymph nodes and white pulp of spleen.
After differentiation, T cells are able to migrate in to other tissues.
They alter their pattern of expression of adhesion molecules. CCR7 binds to ligands in lymphoid tissues and then after differentiation T cells lose expression of this molecule, which allows them to disassociate from the lymph node

Question 5

What are the determinants of immunological memory

Answer 5

Expansion
Contraction
Reprogramming
Memory duration
Memory vs. Exhaustion

Question 6

What role do CD4 cells play in CD8 activation?

Answer 6

CD4 helper cells can condition the dendritic cell to properly activate the CD8 T cell.

Question 7

What is the hallmark change in T cell differentiation?

Answer 7

A change in cytokine production due to a change in gene expression. This is regulated intracellularly by key transcription factors such as STAT, Notch, NF-kb & Forkhead

Question 8

Describe STATs

Answer 8

Signal Transduction and Activation of Transcription (STAT)
Ligand will bind to receptor –> activate JAK –> phosphorylate STAT –> STATs dimerise –> Enter nucleus and alter gene transcription

Question 9

What can effector T cells be identified by?

Answer 9

Cytokine production
Naive T Cell –> IL-2
Th-1 T Cell –> IL-2 & IFN-gamma
Th-2 T Cell –> IL-2 & IL-4

Question 10

Describe Th1 cells

Answer 10

Drive Inflammation
Activate macrophages
Activate DCs
Kill intracellular pathogens (mycobacteria)

IFN-gamma
Lymphotoxin-a

Question 11

Describe the Induction of Th1 cells

Answer 11

Cell-cell contact with DC and release of cytokines (IFNgamma & specifically, IL-12) will stimulate the naive T cell to becoming an Th1 cell.

Question 12

Describe the differentiation of Th1 cells

Answer 12

STAT4 & STAT1 transduce and deliver the signal of IL-12 (via the IL-12 receptor). STAT4 & STAT1 promote transcription of T-bet (a master transcriptional regulator) which will promote differentiation of naive T cell to a Th1 helper cell

Question 13

Describe Th2 helper cells

Answer 13

Activate B cell proliferation
Class with recombination to IgE
Stimulate Eosinophil recruitment and activation
Stimulate Mucosal secretion

IL-4 (Key)
Various other interleukins

Question 14

Describe Induction of Th2 Cells

Answer 14

Cell-Cell contact with DC and release of cytokines (namely IL-4) will stimulate the naive T cell to become a Th2 helper cell.
IL-4 is the hallmark cytokine produced by Th2 cells but is also required for the differentiation into a Th2 cell

Question 15

Describe Th2 helper cell differentiation

Answer 15

STAT6 transducer and deliver the signal of IL-4 (via the IL-4 receptor). STAT6 promotes transcription of GATA-3 (the major transcriptional regulator of Th2 cells). This will promote differentiation of the naive T cell to a Th2 helper cell.

Question 16

Compare Th1 & Th2 differentiation

Answer 16

Major activating cytokine
  - Th1: IFN-gamma
  - Th2: IL-4
Transcription Factor
  - Th1: STAT1 & STAT4
  - Th2: STAT6
Major Transcriptional Regulator
  - Th1: T-BET
  - Th2: GATA-3
Signature Cytokine
  - Th1: IGN-gamme
  - Th2: IL-4

Question 17

Describe amplification loops as they relate to Th2 differentiation

Answer 17

As IL-4 is the cytokine required to initiate Th2 differentiation but is also the major cytokine produced by Th2 helper cells, there is a positive amplification loop on Th2 differentiation.

Question 18

Describe Th17 cells

Answer 18

Recruit and activate neutrophils
Extracellular bacteria and fungi

IL-17 its signature cytokine

Question 19

Descrive Th17 differentiation

Answer 19

Many extracellular cytokines (IL-6, IL-1beta) signal for Th17 differentiation.
These cytokines signal through STAT3.
STAT3 activates the master transcriptional factor RORgammaT

Question 20

Compare the differentiation of Th1, Th2 & Th17 cells

Answer 20

Major activating cytokine
  - Th1: IFN-gamma
  - Th2: IL-4
  - Th17: IL-1beta, IL-6
Transcription Factor
  - Th1: STAT1 & STAT4
  - Th2: STAT6
  - Th17: STAT3
Major Transcriptional Regulator
  - Th1: T-BET
  - Th2: GATA-3
  - Th17: RORgammaT
Signature Cytokine
  - Th1: IGN-gamme
  - Th2: IL-4
  - Th17: IL-17
Affected Pathogen Type(s)
  - Th1: Intracellular bacteria
  - Th2: Helminths
  - Th17: Extracellular bacteria, Fungi

Question 21

Describe Regulatory T Cells

Answer 21

A population of T cells that regulate the activation or effector mechanisms of other T cells and may be necessary to maintain tolerance to self antigens.

Question 22

Describe Treg cell differentiation

Answer 22

Many extracellular cytokines (IL-2, TGF-beta) signal for Treg differentiation.
These cytokines signal through STAT5.
STAT3 activates the master transcriptional factor for Treg differentiation, FoxP3

Question 23

Describe Tfh Differentiation

Answer 23

Many extracellular cytokines (IL-6, IL-6) signal for Tfh differentiation.
These cytokines signal through STAT3 & STAT4.
STAT3 & STAT4 activate the master transcriptional factor BCL6
The signature cytokine of Tfh cells is IL-21