Activation and differentiation of CD4+ T cells

Question 1

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

Answer 1

• CD4+ T cell
• Antigen
• Antigen presenting cell= dendritic cell

Question 2

Where does T cell activation occur?

Answer 2

Lymphoid tissue- lymph node

Question 3

What is signal 1?

Answer 3

T cell recognising antigen

Question 4

Why is T cell recognition of antigen not enough to activate them?

Answer 4

Some antigens presented may be self or harmless antigens so a reaction to them would cause autoimmune disease or allergy.

Question 5

What is signal 2?

Answer 5

Interaction between co-stimulatory molecules (between dendritic cell and T cell)

Question 6

Examples of co-stimulatory molecules

Answer 6

CD28 on T cell

CD80/CD86 on dendritic cell

Question 7

What happens to co-stimulatory molecules when a pathogen is present?

Answer 7

They are up-regulated. DCs recognise pathogen associated molecules via PRRs which activates MHCII and the antigen which causes the up-reguation of CD80 or CD86.

Question 8

What happens if a T cell recognises an antigen but doesn’t get co-stimulated?

Answer 8

The T cell becomes anergic= unresponsive to antigen

Question 9

What is an example of an inhibitory pathway to prevent T cell activation?

Answer 9

CTLA-4 inhibits the CD28-CD80/86 interaction which limits T cell activation.

Question 10

What is a positive and negative of CTLA-4 function?

Answer 10

• It limits T cell activation against self antigens

- Can limit T cell responses during chronic infection and against tumours.

Question 11

Example of important adhesion molecules for T cell:DC interaction.

Answer 11

LFA-1:ICAM-1 interactions allow loose adhesion between the two cells. If the T-cell recognises the antigen then signalling events make the molecules bind with higher affinity so more TCR/MHCII interactions can occur.

Question 12

What happens if the T cell does not recognise the antigen?

Answer 12

The loose LFA-1:ICAM-1 interactions are not strengthened so the T cell moves on to look for another DC.

Question 13

What are clusters of molecules at the T-cell/DC interface called?

Answer 13

Supramolecular activation clusters (SMACs)

Question 14

How does antigen binding and co-stimulation cause T cell activation?

Answer 14

Signal 1 and 2 trigger signals inside the T cell which alter gene transcription and drive T cell activation and differentiation.

Question 15

What happens when a CD4+ T cell is activated?

Answer 15

T cell are first stimulated to proliferate to increase the number of antigen-specific T cells. This is called clonal expansion.

Question 16

How does clonal expansion work?

Answer 16

Activated T cells express the receptor for IL-2 on their membranes. This acts in an autocrine and paracrine manner to drive T cell proliferation.

Question 17

What is the definition of cytokines?

Answer 17

Small protein released by cells that have specific effects on interactions between cells, on communications between cells or on the behaviour of cells.

Question 18

Types of cytokines

Answer 18

• Intreleukins
• Interferons
• Colony stimulating factors

Question 19

What are the two sub-classes of CD4+ T cells and what do they respond to?

Answer 19

Th1 cells- responses to intracellular pathogens

Th2 cells-responses to extracellular responses

Question 20

How are Th1 cells characterised and what do they do?

Answer 20

Characterised by production of: IL-2, interferon gamma and lymphotoxin.

• Activates macrophages
• Stimulates CD8+ T cells (killer cell)
• Stimulates B-cells to produce opsonising antibodies.

Question 21

How are Th2 cells characterised and what do they do?

Answer 21

Characterised by production of: IL-4, IL-5, IL-9 and IL-13.

• Stimulates B-cells to produce neutralising antibodies
• Attract and activates eosinophils and basophils.

Question 22

How are different Th cells made?

Answer 22

Need signal 3= cytokine signal to the T cell

Question 23

What is signal 3 for Th1 cells?

Answer 23

-IL-12
-IFN-gamma
Positive feedback means you always make more

Question 24

What is signal 3 for Th2 cells?

Answer 24

• a number of cytokines from epithelial cells

- IL-4

Question 25

How are Th cells regulated?

Answer 25

Th1 and Th2 cross-regulate each other

• Th1 cells down regulate the production of Th2 by the secretion of IFN-gamma
• Th2 cells down regulate the production of Th1 by the secretion of IL-4.

Question 26

What are some of the harmful properties of Th1 and Th2?

Answer 26

Th1: autoimmunity and transplantation rejection
Th2: allergy and autoimmunity

Question 27

What do Th cells acquire during differentiation which enables them to migrate?

Answer 27

Homing molecules

Question 28

What are some newly discovered CD4+ T cell subsets?

Answer 28

Novel effector CD4+ T cell subsets- help fight infection:

• Th17
• T follicular helper cells

Regulatory T-cells (Tregs)- help suppress responses

Question 29

What is the function of T follicular helper cell?

Answer 29

They are helper cells specialised to of to the B cell follicles (germinal centres) of lymph nodes to help B cells make antibodies.

Question 30

What do Tregs do?

Answer 30

Suppress the activity of T cells which bind to self-antigens to prevent autoimmunity.

Question 31

What are the two ways in which Tregs are made?

Answer 31

Made in the thymus as part of normal T cell development

Made in peripheral tissues/organs by naive CD4+ T cells via IL-2 and TGF beta to produce induced of peripheral Tregs.

Question 32

How do Tregs inhibit harmful T cells?

Answer 32

• anti-inflammatory cytokines
• outcompete effector T cells for resources
• kill self-reactive T cells