L17 - T-Cell Activation & Generation of Effector T-cells

Question 1

Describe Naive T-cell recirculation and activation?

Answer 1

They are released from thymus and enter the blood circulation. Thye enter a lymph node via a high endothelial venule.

They sometimes enter lymph nodes where is no antigen that is specific for the T-cell receptor, so it moves in and out of different lymph nodes until it encounters an antigen that it binds to.

This is usually at an infected site, which attracts dendritic cells that enter the lymph nodes. When T-cell binds to antigen, it receives the necessary signals from the dendritic cells and become an activated T-cell

activated T-cells move into circulation via thoracic duct of the vena cava, and move into sites of infection

Question 2

State some APCs that activate T-cells?

Answer 2

Dendritic cell
Macrophages
B-Lymphocytes

Question 3

What 3 signals are needed for T-cells to be activated/differentiated into
effector T cell?

Answer 3

To be fully activated and differentiated into
effector or memory T cell, the T cell needs 3
different signals:
• Signal 1: Antigen recognition
• Signal 2: Co-stimulation
• Signal 3: Cytokines

Question 4

Where is the Co-stimulatory signal located?

Answer 4

Most commonly of dendritic cells but also provided by macrophages or B-cells

Question 5

What is the co-stimulatory signal?

Answer 5

B7:CD28

CD28 expressed by T-cell

B7-1 (CD80) and B7-2 (CD86) molecules are expressed by the APC

Question 6

How is CD40 involved in T-cell activation?

Answer 6

CD40 ligand binds to CD40 on Dendritic cells. This causes Dendritic cells to express B7. Activated DCs stimulate proliferation and differentiation of T-cells

Question 7

Describe the effects of negative co-stimulation of activation of T-cells?

Answer 7

CD80 and CD86 also bind to CTLA-4, which is the master regulator for T-cell activation. It sends a string negative signal to the T-cells

Question 8

What is CTLA-4 and what is the purpose ?

Answer 8

CYTOTOXIC LYMPHOCYTE ANTIGEN 4:

negative regulation of immune response

Reduce the inflammation after the infection has cleared

Question 9

When is CTLA-4 expressed

Answer 9

CTLA-4 is expressed approx 2-3 days

post stimulation

Question 10

For what components does CTLA-4 have high affinity for?

Answer 10

It has high affinity/avidity for CD80 but
opposing effects to CD28.

Therefore, competes favourably with
CD28 for ligation to CD80/86

Question 11

Describe the Induction of T-cell polarisation

Answer 11

Dendritic cells release cytokines, that could drive the T-cell into helper type 2 (TH2) or into helper type 1 (TH1)

Question 12

Describe the IL-2 induction of T-cell proliferation and how is it controlled?

Answer 12

IL-2 is important in activating and sustaining T-cell proliferation.

T-cell once activated, produces a lot of IL-2, which provides autocrine signalling for T-cells to allow for proliferation.

Regulatory T-cells have a higher concentration of IL-2 receptors on their surface, so they can sequester IL-2, to block this process

Question 13

Describe the expression of surface molecules on T-cells over time?

Answer 13

Naive T-cell = TCR

Retention in Lymph Node = TCR, CD69

Proliferation = TCR, CD69, IL-2Ralpha (CD25)

Activation of dendritic cells, macrophages and B-cells = TCR, CD69, IL-2Ralpha, CD40 ligand

Control of Response = TCR, CD69, IL-2Ralpha, CD40 ligand, CTLA-4

Question 14

What can a Naive CD4+ T-cell differentiate into?

Answer 14

Effector CD4+ T-cell

or

Memory CD4+ T-cell

Question 15

What can a Naive CD8+ T-cell differentiate into?

Answer 15

Effector CD8+ T-cell

or

Memory CD8+ T-cell

Question 16

What is the role of an effector CD4+ T-cell?

Answer 16

Activation of Macrophages, B-cells and other cells; inflammation

Question 17

What is the role of an effector CD8+ T-cell?

Answer 17

Killing of infected cells an Macrophage activation

Question 18

What will a naive T-cell do post TCR signalling?

Answer 18

Modify the expression of surface
molecules

Upregulate cytokine production

Undergo active rounds of
proliferation

Upregulate expression of pro-survival
genes

Upregulate expression of IL-2 and IL-2R-a

Differentiate into effector or
memory cells

Question 19

How does TH1 polarisation occur and what is the TF that controls differentiation?

Answer 19

TH1 polarisation occurs in 
response to the presence of 
intracellular pathogens such as 
viruses and bacteria that are 
ingested by and destroyed by 
phagocytes.

Master transcription factor that
controls differentiation – T-bet

Question 20

What is the function of TH1 Cells?

Answer 20

They produce IFNg

Help to activate
macrophages to ingest and
destroy microbes

Induce antibody class 
switching to IgG 
(opsonization).

All helpful response in
eliminating an intracellular
pathogen

Question 21

How does TH2 polarisation occur and what TFs are involved?

Answer 21

TH2 polarization occurs in
response to phagocyte -
independent immune responses. (presence of parasites)

TH2 polarizing cytokine is IL-4,

Transcription factors: IL-4
activates STAT6 which promotes
expression of GATA 3

GATA 3 is a transcriptional
activator of IL-4 and IL-13 genes

Question 22

What is the function of TH2 Cells?

Answer 22

TH2 cells produce IL-4, IL-5 
and IL-13, effector cytokines 
that help eliminate 
extracellular parasitic 
infections such as worms

Promote class switching to 
IgE, which causes 
inflammatory cytokines to be 
released by eosinophils and 
mast cells.

They also increase intestinal
movement and mucus
production.

IgE also mediates allergy

Question 23

Which cells produce IL-4?

Answer 23

• Dendritic cells do not make IL-4
• Eosinophils, basophils and mast cells
produce IL-4. ILCs also produce IL-4