L9 - Activation and differentiation of T cells I

Question 1

What are the basic components needed for CD4+ T-cell activation?

Answer 1

Antigen

CD4+ T-cell

APC (ie dendritic cell) for Naive cells

Question 2

How do Naive T-cells cells enter lymph nodes and where exactly do they enter?

Answer 2

High endothelial venules (HEVs) - Naive T-cells are attracted to HEVs through their receptors (ie chemokine receptor CCR7 being attracted to CCL21 in HEVs)

Artery

Question 3

How do dendritic cells enter lymph nodes and where exactly do they enter?

Answer 3

Activated dendritic cells enter the lymphatic system due to attraction (ie via CCR7 on DC being attracted to CCL21)

Afferent lymphatic vessel

Question 4

Paracortical area: what is the significance of this with T-cells and dendritic cells?

Answer 4

Cells migrate to and communicate in paracortex

Question 5

What happens to T-cells and dendritic cells after communicating in the paracortex?

Answer 5

T-cells leave lymph node via the lymph and re-enter circulation via thoracic duct

Dendritic cell will stay in lymph node for a couple of days and then die

Question 6

Do some dendritic reside within lymph nodes?

Answer 6

Resident DCs - remain in the paracortex all the time where they can capture and present antigens draining into the lymph nodes from the tissue via lymphatics

Question 7

Why are T-cells not activated upon every antigen binding to them?

Answer 7

Some antigens presented by dendritic cells will be self or harmless antigens

If CD4+ T-cells are activated by them, would trigger autoimmune disease/allergy

• Only want to react to dangerous antigens

Question 7

How do dendritic cells detect which antigens are from harmful cells>

Answer 7

DCs recognise pathogen-associated molecules via Pattern Recognition Receptors (PRRs)

Question 8

Anergic: what is it and why is it useful?

Answer 8

T-cell becoming unresponsive to an antigen

Good way of stopping T-cells from getting activated by self-antigen

Question 9

How do T-cells get activated against harmful antigens?

Answer 9

Cell adhesion events are important in supporting T-cell activation, one such example:

• LFA-1:ICAM-1 interactions allow loose adhesion between the CD4 T cell and the DC, allowing T cells to come into close contact with DCs (to ‘sample’ antigens)
• CD4 molecule on the T cell can interact with the MHC Class II molecule on the DC
• Activation through the T-cell receptor complex begins (signal 1), leading to signalling events that make the LFA1 and ICAM1 molecules bind with higher affinity
• More T-cell and dendritic cell interactiions occur

Question 10

What is the term given to the location where T-cells and dendritic cells meet?

Answer 10

Immunological synapse

Question 11

SMACs: what are they?

Answer 11

Supramolecular activation clusters - clusters of molecules at the T-cell-DC interface

(Occur between T-cells and DCs)

Question 12

Activated T-cell signalling: how does it work?

Answer 12

Four intracellular signals triggered

T-cell receptor cannot signal directly, must interact with the CD3 complex which works with the secondary signals to signal through the cell and alter gene transcription

Question 13

T-cell activity after activation

Answer 13

• Proliferation stimulated - number of antigen specific T cells increases
• Begin to express IL-2 receptor on their membranes
• Begins to secrete cytokine interleukin 2 (IL-2)
• Autocrine and paracrine activation

Question 14

T-cell clonal expansion after activation

Answer 14

• In 3-4 days, there is a 10,000-100,000 fold increase in the numbers of antigen-specific CD4+ T-cells
• The CD4+ T-cells also start to differentiate into effector cells
• All goes on in the lymph nodes or spleen