Immunology 7- Effector T Lymphocytes

Question 1

Define Naïve T cells:

Answer 1

mature recirculating T cells that have not yet encountered antigen

Question 2

Effector T cells:

Answer 2

encountered antigen, proliferated and differentiated into cells that participate in the host defense

Question 3

Memory T cells:

Answer 3

Encountered antigen, contracted, rea [dy to respond to future infections.

Question 4

Target cells:

Answer 4

Cells on which effector T cells act

Question 5

How can T cells enable other cells to function better

Answer 5

They are large producers of cytokines and chemokines - they can affect the function of other cells

They can cause better digestion and better killing

Question 6

What is the role of the Dendritic cells

Answer 6

DC exist in tissues (surveillance) acquire antigen, move to lymph nodes (needs activation by PAMP/ PRR)

Question 7

What is the role of HLA-B57

Answer 7

it presents a single peptide from one of the HIV proteins - that peptide is key to the function of the viral protein and so the CD8 cells kill any cells with that epitope.

Question 8

Describe what happens when a dendrite interacts with an infected cell

Answer 8

1. Cell infected
   DC collects material
   Moves to the lymph nodes
2. MHC:peptide
   TCR interaction
3. Naïve T becomes effector
4. Effector cell sees MHC:Peptide on infected cell
   Performs function
5. Effector pool contracts to memory

Question 9

How do Activated T-cells know where the site of infection is

Answer 9

Chemokine gradient - so if the cells express the right chemokine receptors they can follow these gradients

Adressins and Integrins - allows the cells to move out of the vessels

Question 10

What are the 3 signals required for a response from T-cells

Answer 10

Antigen Recognition
Co-stimulation
Cytokine Release

Question 11

Function of CD8+ T cells - Cytotoxic T Lymphocytes

Answer 11

Their main role is to target and kill infected cells

When a virus peptide is presented on the MHC Class I of a cell, the effector CTL identifies the MHC I with a foreign peptide and kills it.

Necrosis - inflammatory cell death (this is a classic danger signal)

Apoptosis - programmed cell death (instead of exploding outwards, it collapses in on itself)

Specific recognition of target cells by cytotoxic effectors causes polarisation of cytotoxic vesicles within the cell.

This causes release of granules by T cells

This induces apoptosis in targets

Question 12

Cell mediated cytotoxicity

Answer 12

Perforin + Granzyme -
CD8 injects perforin into the membrane of the target cell. This makes a pore in the membrane and allows granzyme to enter the cell.

Fas-fas Ligand
Fas ligand (FasL) = on the CD8 cell
Fas Receptor = on the target cell
When Fas has been engaged - it releases caspases

Both of these pathways upregulate CASPASE within the target cell which drives apoptosis.

Question 13

range of effector functions of cd4 t cells

Answer 13

Macrophage activation

Delayed Type Hypersensitivity Response

B cell activation

Regulation

Question 14

What are the 5 families of T helper cells:

Answer 14

Th1 - pro-inflammatory (boosts cellular response, produce IF gamma and activates macrophages)

Th2 - boosts anti-multicellular organism responses

Follicular helper T cells - essential for generation of isotype-switched antibodies

Th17 - important for control of bacteria

Treg - T cells that regulate the activation or effector functions of other T cells

Question 15

What are t helper cells defined by

Answer 15

the cytokines they produce and the transcription factors they use

Question 16

Macrophage Activation

Answer 16

They get activated by CD4 T cells which enable them to engulf and kill pathogens better

Once activated, they increase the levels of pro-inflammatory molecules: TNF-a and CD40

T cells and macrophages cross-talk - via cytokines

Question 17

Function of Delayed Type Hypersensitivity

Answer 17

Seems pathological but it is protective as well

MAIN ROLE: defence against intracellular pathogens

If the antigen isn’t eradicated - you get chronic stimulation and granuloma formation

If the antigen is NOT A MICROBE, delayed type hypersensitivity produces tissue injury without protection = ‘hypersensitivity’

Question 18

2 Phases of Delayed Type Hypersensitivity

Answer 18

Sensitisation - you have to be exposed to the antigen first before becoming allergic to it. No one is allergic to anything without being exposed to it once.

Effector - on second exposure you can trigger a severe response

Question 19

How do helper T-cells cause Delayed Type Hypersensitivity

Answer 19

It is due to pronounced secretion of cytokines by helper T cells activated by the antigen in the area. The cytokines act as inflammatory mediators and also activate macrophages to secrete their potent mediators. It takes several days to develop so it is known as delayed type hypersensitivity.

Immediate Hypersensitivity is caused by mast cell degranulation

Question 20

In general what does a cd4 t helper cell do

Answer 20

their role is to turn off or turn on the response of other cells by producing cytokines

Question 21

B cell activation

Answer 21

B cells only take up the antigen that they recognise whereas DCs take up a large variety of antigens

The antigen presents by both DC and B cell will be the same so they will both present the same peptide-MHC complex which can be recognised by the T cell

The T cell will go from naïve to the effector state - it will recognise the antigen-MHC complex on the B cell and activate it

Question 22

Difference between T cell memory and B cell memory

Answer 22

T cells don’t undergo isotype switching or affinity maturation

Once a T cell response has been made, it stays the same. B cell responses improve over the time.

Memory T cells are different from naïve T cells - as a memory cell they change the type of cytokine receptor they have on the cell.

Question 23

Two subsets of memory T cells

Answer 23

Effector Memory - memory is local to the site of infection - the effector memory cells will live in the lungs if you’ve had lung infection

Central Memory - go back to the spleen or lymph nodes. Longer lasting but slower to activate response.

Question 24

T cell exhaustion

Answer 24

Over time, especially in chronic infections, the CD8 pool contracts

This is a particular problem when the infection isn’t cleared e.g. HIV, CMV

Cells start to exhibit PD1 (programmed death) receptors which makes it much harder to activate T cells