T cell activation via a messenger

Question 1

What is the messenger that activates a T cell?

Answer 1

Dendritic cell: the key antigen presenting cells. They deliver 3 signals

1) Peptide/MCH
2) These have co-stimulatory molecules which help activate the naive T cell.
3) Dendritic cell secrete IL6, IL12 to T cells to determine their differentiation.

Question 2

What is the messenger that activates a T cell?

Answer 2

Dendritic cell: the key antigen presenting cells.

These have co-stimulatory molecules which help activate the naive T cell.

Dendritic cell secrete IL6, IL12 to T cells

Question 3

What receptor recognises PAMPs (of microbes) on Naive Dendritic cells?

Answer 3

Toll-like receptors.

Activation turns on a kinase cascade and Transcription factors (IRNs) which cause the up-regulation of co-stimulatory molecules on dendritic surface.

This drives maturation of DC.

Question 4

What is DC maturation>

Answer 4

The transformation from antigen capturing antigen to a cell that present antigen to engage the T cells.

Lots of different processes that are needed at lots of different times.

Question 5

Describe an experiment which

Answer 5

Grown DC cells from bone marrow of mouse.
When they sense microbial product they increase their capture of material from the surrounding environment.

Add LPS, toll like receptor ligand, the activity increases. Cells membrane ruffling and cells fill up with endosome due to large amount of pathogen antigen endocytosis into the cell.

Antigen and LPS at the same time causes more T cells activation compared to Antigen added before LPS.

Measures IL-2 production by T cells; more cytokine, more T cell stimulation.

Question 6

What are the different ways DC can take up antigens

Answer 6

To be presented to CD4+ on MCH2

1) Macropinocytosis
3) Receptor-mediated endocytosis

To be presented on CD8+ on MHC1
3) virus infection

Question 7

What are the different ways DC can take up antigens

Answer 7

To be presented to CD4+ on MCH2

1) Macropinocytosis
3) Receptor-mediated endocytosis

To be presented on CD8+ on MHC1
3) virus infection in DC cell

Question 8

How is the innate detection system vulnerable?

Answer 8

Viruses may evade dendritic cells and CD8+ T cell are not made.

Question 9

What is cross presentation?

Answer 9

The presentation of exogenous antigens, to get into cytosol by a endocytic pathway, and loaded on to MHC1 instead of the normal MHC2.

Question 10

What receptor recognises PAMPs (of microbes) on Naive Dendritic cells?

Answer 10

Toll-like receptors.

Toll receptors sense inside and outside the cell

Activation turns on a kinase cascade and Transcription factors which cause the up-regulation of co-stimulatory molecules on dendritic surface; it drives DC maturation.

Question 11

Give examples of Toll-like receptors and whether they are outside or inside the DC cell.

Answer 11

On outside:

• TLR4: which recognises LPS
• TLR1/2: sense other bacterial antigens

On inside: TLR3: which recognises nucleic acid signatures unique to pathogens within the endosome.

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Question 12

Describe what happens to a DC after binding to pathogen via TLR

Answer 12

1) Increases antigen capture
2) Increases MHC production so more translocate to DC surface
3) Increases co-stimulatory molecule production
4) Increase cytokine production (IL6, IL12)
5) Increases expression of CCR7 a chemokine receptor

Question 13

What are some co-stimulatory molecules?

Answer 13

• CD80
• CD86
• CD40

Question 14

What does receptor CCR7 expression on DC surface lead to? Why is it important?

Answer 14

This is important for the DC to be guided to lymphoid tissues by following a gradient of chemokines called CCL21.

No CCR7 receptor means the DC cannot move out of tissues.

Question 15

What does receptor CCR7 expression on DC surface lead to? Why is it important?

Answer 15

This is important for the DC to be guided to lymphoid tissues by following a gradient of chemokines called CCL21.

No CCR7 receptor means the DC cannot move out of tissues to lymph nodes to stimulate T cells.

Question 16

Describe how T cells enter the lymph nodes.

Answer 16

Lymph nodes are interconnected; upstream and downstream.

There are two sources of T cells: cells from blood or cells from upstream afferent lymph nodes enter a lymph node across the high endothelial venules (HEV) in the cortex; they then look for specific antigen which is very rare to find its match.

If not in one lymph node, antigen may be in next lymph node.

Question 17

What is the role of adhesion molecules?

Answer 17

1) T cell Binds to DC via LFA-1 on T cell and ICAM-1 on DC. This is weak affinity.
2) The binding of the TCR and MHC signals to LFA-1 on T cell to change conformation. This is called inside out signalling.
3) Conformational change increases affinity for DC ICAM-1 and prolongs cell contact. This is strong binding

Question 18

What strengthens adhesion binding?

Answer 18

The T cell TCR binding to MHC-peptide complex.

Question 19

What increases expression of B7 molecules on DC cells? What does it bind to?

Answer 19

Activated Toll like receptor signalling receptor on DC.

B7 binds to CD28 on naive T cell.

Question 20

How do co-stimulators (DC signal 2) link innate and adaptive immune system?

Answer 20

It is regulated by pathogen signals

Question 21

How does T cell differentiation work?

Answer 21

Cytokine environment in lymph node cytokine environment is important for turning on different transcription factors in T cell to differentiate activate production of other cytokines that effect other cells as a helper or a killer.

For example, cytokine TGF-beta from DC, activates T cell to become regulatory T cell and acivates its TF called FoxP3 which causes cyokines TGF, IL10 to be made by the T cell.

Question 22

What do mature Th1 cells do once activated by an immature effect T cell?

Answer 22

Th1 release IL2, IFN which effects macrophages, B cell activation, oposizing antibodies

Question 23

What do mature Th2 cells do once activated by an immature effect T cell?

Answer 23

Th2 release IL4, IL5 which activate B cells to make antibodies

Question 24

What is the pathway that leads to B cell/ antibody activation?

Answer 24

DC activate naive cells in T cell zone of lymph nodes via antigen.

B cells from blood that are activated with the same antigen present to helper T cell in the T cell zone.

They form conjugates with specific T cells

Question 25

What happens if there is no signal 2; there is no co-stimulation?

Answer 25

T cell becomes anergic. T cell is not stimulated.

Tolerance: if DC has not upregulated co-stimulatory molecule, T cell become unresponsive

Question 26

How do vaccines relate to co-stimulatory molecules? What are adjuvants?

Answer 26

Vaccines have to induce co-stimulatory signal through the use of ADJUVANTS as well as MHC-peptide antigenic component in order to activate T cells.

Adjuvants induce signal 2.

Question 27

What happens if there is no signal 2; there is no co-stimulation?

Answer 27

T cell becomes anergic. T cell is not stimulated.

Anergy is a form of Tolerance: if DC has not upregulated co-stimulatory molecule, T cell become unresponsive as this not the correct binding is was educated to recognise.

Question 28

How do vaccines relate to co-stimulatory molecules? What are adjuvants?

Answer 28

Vaccines have to induce co-stimulatory signal through the use of ADJUVANTS as well as MHC-peptide antigenic component in order to activate T cells.

Adjuvants induce signal 2.and cells become anergic/unresponsive.

Question 29

What is an example of a good adjuvants?

Answer 29

Heat-killed microbes

Question 30

What are the two stages of the adaptive immune response?

Answer 30

Stage 1: DC activate naive T cells to proliferate and differentiate into effector cells.

Stage 2: T cells carry out effector function

Question 31

What are some effector functions of CD8+ and CD4+ AFTER DC activation?

Answer 31

CD8+ will travel to site of infection and cells die via apoptosis; Th1 CD4+ travel to site of infection to activate macrophage to kill; Th2 CD4+ interact with specific B cells in lymphoid tissue to make antibodies.

Question 32

What is one strategy to eradicate tumours?

Answer 32

Tumours don’t express co-stimulatory molecules so T cells are not activated.

-Grown cancer patients blood DC in vitro, incubate with tumour material, and reinfuse to attempt to re-stimulate CD8+ killing response.

Question 33

What does alloreactive T cells refer to in terms of acute direct recognition?

Answer 33

T cells that are not educates/tolerised to the new peptides from new graft transplant. Graph cell presents its foreign antigen. T cells destroy organ/graft.

Question 34

How does matching transplant organ to blood type help slow rejection in terms of indirect allorecognition pathway.

Answer 34

Indirect pathway of rejection via APC recognition of DEAD graph cell with its MHC variants/allotyoes containing graph protein antigen. APC cell takes up which are displayed by its own MHC molecules as a processed foreign antigen.

Question 35

What are anti-HLA antibodies in terms of indirect allorecognition pathway?

Answer 35

Host B cell (APC) can take up graph MHC as it looks forign. B cell processes and presents, receives help from T cell which allows it to become a plasma cell and produce HLA-antibody?

Question 36

What are anti-HLA antibodies in terms of indirect allorecognition pathway?

Answer 36

Host B cell (APC) can take up graph MHC as it looks forign. B cell processes and presents, receives help from PHYSICALLY LINKED T cell which allows it to become a plasma cell and produce HLA-antibody that attack graph MHC molecules.