T cell subsets and function

Question 1

How does MHC1 work?

Answer 1

• proteosome cuts protein into peptides to fit into MCH groove then go to Golgi apparatus onto the surface

Question 2

What does MHC2 do?

Answer 2

• MHC2 takes in antigen from outside into phagolysosome

Question 3

How do T cells develop?

Answer 3

1. T cell development starts in the bone marrow (lymphoid lineage)
2. Thymocytes then migrate to thymus
3. In the thymus, TCR genes will rearrange
4. Decision of whether to be CD4/8 T cells is made
5. undergo positive and negative selection to remove autoreactive T cells > migrate to periphery

Question 4

Where are CD4-8 activated?

Answer 4

• naïve CD4/8 cells both activated in secondary lymphoid tissues by DCs
• cross-presentation is critical

Question 5

What do T cells do upon activation and what is this aided by?

Answer 5

• Upon activation T-cells proliferate
• this is aided by the production of the cytokine IL-2

Question 6

What do activated T-cells produced and express a higher affinity of?

Answer 6

• produce IL-2
• activated T cells also express Higher affinity IL-2 receptor

Question 7

IL-2 drives T-cell proliferation - How does this happen?

Answer 7

• clonal expansion of T cell with correct TCR
• cytokine can act on cell producing it (autocrine)
• cell lineages differentiate into effector or memory cells

Question 8

After activation where are CD4 T cells held and when do they leave?

Answer 8

• After activation T cells are held in lymph node
• after differentiation they are more likely to leave

Question 9

What so CD8 T cells do after activation?

Answer 9

• leave the secondary lymphoid tissues and re-enter circulation
• alter their homing receptors to target inflamed endothelium
• search for infected host cells by checking MHC1 presentation

Question 10

How do CD8 T cells kill host cells?

Answer 10

• via inducing apoptosis
• this is done by the release of molecules such as perforin, granzymes, granulysin
• or Fas or FasL recptor interaction

Question 11

After proliferation helper T cells can differentiate into 5 (range) of subsets - what are these?
NB. depends on signals received

Answer 11

1. Th1 cells
2. TH2 cells
3. TH17 cells
4. T reg cells
5. TFH cells

Question 12

What do the T helper subsets do?

Answer 12

= secrete cytokines to impact on other immune cells

Question 13

Differentiation (Signal 3) depends on a number of factors - what are these?

Answer 13

• cytokines produced by innate immune response
• cytokines produced by the APC
• Bystander cytokines

Question 14

Differentiation into Th1 is promoted by a signal containing what?
What transcription factors are activated here?

Answer 14

• INF-y
• IL-12
• transcription factors activated = STAT1, Tbet

Question 15

Where do Th1 cells predominate?

Answer 15

• these predominate in acute inflammatory responses and viral infections

Question 16

What is the function of Th1 cells?

Answer 16

• to secrete INF-y, IL-2 and TNF-a

Question 17

What do the secretions from Th1 cells lead to?

Answer 17

• activate macrophages
• class switching to IgG (opsonizing Abs)
• increased NHC class 1 and II expression
• promotes NK cell activity
• proinflammatory

Question 18

What are the main targets for Th1 cells?

Answer 18

• activating macrophages to migrate
• killing infected macrophages
• increased MHC class I

Question 19

What are Th1 cells critical in?

Answer 19

• critical for intracellular infections such as viral diseases

Question 20

What is differentiation into Th2 promoted by?
What are the transcription factors activated?

Answer 20

• Prompted by a signal 3 containing IL-4
• transcription factors activated = STAT6, Gata3

Question 21

What is the function of Th2 cells?

Answer 21

• to secrete IL-4, IL-5, IL-13

Question 22

What do the secretions from Th2 lead to?

Answer 22

• B cell proliferation and antibody production
• antibody class switching to IgE
• mucus production

Question 23

What does IL-4 secretion from Th2 cells do?

Answer 23

• simulates B cell growth
• activates mast cells

Question 24

What does IL-13 secretion from Th2 cells do?

Answer 24

• stimulates B cell growth
• supress some macrophage functions

Question 25

What does IL-10 secretion from Th2 cells do?

Answer 25

- inhibits Th1 cell function - supresses some macrophage functions

Question 26

What does IL-5 secretion from Th2 cells do?

Answer 26

- stimulates B cell growth - activates eosinophils

Question 27

What are the main targets of Th2 cells?

Answer 27

- igE class switching - increased antibody production - activated mast cells and eosinophils

Question 28

What type of infection are Th2 cells important in the response to?

Answer 28

- helminth worms

Question 29

What is differentiation into Th17 promotes by? What is the transcription factor activated?

Answer 29

- signal containing IL-23 also IL- 6, TGF-B - transcription factor activated is RORyT

Question 30

What is the function of Th17 cells?

Answer 30

- to secrete IL-17, IL-21and IL-22

Question 31

What do the secretions from Th17 cells lead to?

Answer 31

- neutrophil recruitment - activation of fibroblasts and epithelial cells to secrete chemokines - important art mucosa and epithelia

Question 32

What is the main target of Th17 cells?

Answer 32

- A pro-inflammatory response

Question 33

Th17 cells are an important response in what pathogens?

Answer 33

= extracellular bacteria = fungi

Question 34

Th17 cells can also be related to hypersensitivities such as?

Answer 34

- rheumatoid arthritis

Question 35

What is differentiation into Treg promoted by? What transcription factors are activated?

Answer 35

- promoted by a signal 3 containing . IL-10 .TGF-B .Both anti-inflammatories - transcription factors activated = FOXP3

Question 36

What is the function of Treg cells?

Answer 36

- secrete IL-10 and/or TGF-B

Question 37

What do the secretions from Treg cells lead to?

Answer 37

- downregulation of Th1 cytokine production - downregulation of MHC class II expression = less T cells activation moving towards resolution - Downregulation of Co-stimulatory molecules

Question 38

What are the main targets of Treg cells?

Answer 38

- regulatory (immunosuppressive activities) - dampening down immune responses (both Th1 and Th2 responses)

Question 39

What are Treg cells important responses to?

Answer 39

- many infections - Failure in many hypersensitivities (autoimmunity)

Question 40

What is follicular T cell (TFH cells) promoted by? What is the transcription factor activated?

Answer 40

- promoted by a signal 3 containing IL-6 - Transcription factors activated = Bcl-6

Question 41

What are the functions of TFH cells?

Answer 41

- CXCR5 (chemokine receptor) on surface – keeps them in B cell follicle - ICOS on surface – key in B cell help - IL-21 – proliferation and differentiation of B cells

Question 42

What do the functions of TFH cells lead to?

Answer 42

- T-cell dependent antibody production