T cell activation and generation of effector T cells

Question 1

How T cells move around the body after they exit the thymus as naïve, self-restricted and self-tolerant T cells?

Answer 1

1. They are released into blood circulation and enter a lymph node through high endothelial venules
2. The cell will then go from lymph node to lymph node until they find a antigen specific for the TCR
3. If a T cell encounters a antigen which would normally come from an infected site, it will be picked up by dendritic cell which will travel to the lymph node and enter through afferent lymphatic vessels
4. If the T cell that happens to be circulating from this lymph node binds this antigen, they’ll then get activated, receive necessary signals by the dendritic cell and become activated
5. Activated T cells move into the circulation through the thoracic duct in the vena cava and would preferentially move onto sites on infection through blood circulation

Question 2

How are naive T cells activated in the secondary lymhoid organs like spleens and lymph nodes?

Answer 2

Question 3

What cells activate naive T cells?

Answer 3

Professional antigen presenting cells:

Question 4

What 3 signals does a T cell need to be activated into a effector or memory T cell?

Answer 4

1. Antigen regognition
2. Co-stimulation
3. Cytokines

Question 5

What 3 signals does a T cell need to be activated into a effector or memory T cell?

Describe how antigen recongition is needed…

Answer 5

Initiates immune response so that the immune response is antigen-specific

• Due to the fact of TCR in T cell recognises the antigen in context of MHC (CD4 and CD8 with class 1 and 2)

In the absence of other molecules on the antigen presenting cell or the T cell, no activation happens

Question 6

What 3 signals does a T cell need to be activated into a effector or memory T cell?

Describe how co-stimulation is needed…

Answer 6

Co-stimulatory signal is most commonly on dendritic cells, but also could be macrophages or B cells

TCR signalling is not enough to activate naïve T cells… co-stimulatory molecules are also required like:

• B7:CD28
  
  • CD28 is expressed by the T cell
  • B7 molecules are expressed by the APC

There can also be negative co-stimulatory molecules - inhibit the downstream effector processes initiated by TCR MHC/peptide interaction.

Question 7

What 3 signals does a T cell need to be activated into a effector or memory T cell?

Describe how cytokines are needed…

Answer 7

Cytokines induce T cell polarisation

Each cytokine will create an environment that will render the T cell that’s be activated to be able to carry out a different function

Question 8

What is IL-2?

Answer 8

• important to sustain T cell activation and T cell proliferation

Master cytokine required to sustain proliferation of T cells upon activation

The T cell gets activated and will start to produce a lot of IL-2 (which provides a autocrine signal to the T-cell to allow for proliferation)

Regulatory T cells have a higher level of receptor for IL-2 and they can hide away the IL-2 to block the process - one way of regulation

Question 9

What do T cells express during the process of activation?

Answer 9

After activation, T cells express CD69 - to retain them in the lymph node

CD25 follows, which is a receptor for IL-2 so is important in proliferation

CD40L follows, which can provide extra activation of dendritic cells, macrophages and B cells

Hours and days after the activation, CTLA-4 which can calm or control the response

Question 10

What is the process of antigen recognition to the effects of CD4 and CD8?

Answer 10

Question 11

What will happen post TCR signalling?

Answer 11

A naive cell will:

• modify the expression of surface molecules
• upregulate cytokine production
• undergo active rounds of proliferation
• differentiate into effector or memory cells

Question 12

What induces T cell polarisation into the different subsets?

Answer 12

The polarising cytokines are generated by stimulating APC

The cytokines produced depends on:

• Maturation and activation status of APC
• Which pathogens or inflammatory mediators were encountered by the APC
• In which environment the encounter takes place

Question 13

What are the different types of effector T cells?

Answer 13

Question 14

What are effector cytokines?

Answer 14

= Produced by T cells to have a particular role in their function and effects on other immune cells

Question 15

What are Th1 cells?

Answer 15

Polarisation occurs in response to the presence of intracellular pathogen

Transcription factor that controls differentiation - T-bet

Function:

• Produce IFNg
• Help to activate macrophages to ingest and destroy microbes
• Induce antibody class switching to IgG

Question 16

What are Th2 cells?

Answer 16

Polarisation occurs in response to phagocyte - independent immune responses (parasites)

Its polarising cytokine is IL-4

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

IL-4 drives the polarisation of the T cell into a Th2 phenotype

Transcription factors are STAT6 and GATA-3

Function:

• Produce effector cytokines that help eliminate extracellular parasitic infections
• Supports Tfh cell and B cell help –> antibody production and mast cell degranulation