Cytokines & T helper Cell Mediated Responses

Question 1

What are Costimulatory signals are required for ?

Answer 1

T-cell activation and proliferation

Question 2

Positive costimulatory receptors facilitate ?

Answer 2

Activation, help turn T cell on e.g. CD28

Question 3

What is meant by Clonal Anergy ?

Answer 3

The inactivation of immune cells resulting from their interaction with antigen in the absence of a second antigen signal

Question 4

Negative costimulatory (coinhibitory) receptors help?

Answer 4

Turn activation off. E.g. CTLA-4 & PD-1 (checkpoint blockade)
- These are important for the treatment of chronic immune-
mediated diseases

Question 5

What are two types of communication in the immune system ?

Answer 5

1. Cell-cell direct receptor 
communication 
2. Cytokine mediated communication - Small, soluble glyoprotein messengers <30 kDa a 
communication network 
for the immune system

Question 6

How can cytokines act specifically ?

Answer 6

• Only cells expressing specific cytokine receptors can be activated
• Short-lived
• High concentrations needed

Question 7

What happens when adaptive immune cells are stimulated by APCs ?

Answer 7

They proliferate & differentiate into effector cells with a range of functions appropriate for the immunological challenge

Question 8

Effector T cell differentiation into functionally distinct

subsets depending on the type of infection?

Answer 8

• Th1 cells
• Th2 cells
• Th17 cells
• Tregs
• TFH cells

Question 9

How does CD4+ T cells help the activity of other immune cells ?

Answer 9

1. Releasing a variety of cytokines with direct effector functions
2. B cell antibody class switching
3. Activation & growth of cytotoxic CD8+ T cells
4. Maximizing bactericidal activity of macrophages

Question 10

What is proliferation and differentiation of naive T cells is driven by ?

Answer 10

Autocrine IL-2

Question 11

What are Tacrolimus (FK506).. Cyclosporin A and Rapamycin (Sirolimus) and what are they used for ?

Answer 11

Immunosuppressive drugs used to mediated T cell mediated rejection of transplants via
inhibition of IL-2 production/signalling

Question 12

What can the Helper T cells be divided into at least five distinct subsets ? and explain what each one does?

Answer 12

• Th1 regulate immunity to intracellular bacteria and viruses
• Th2 regulate immunity to worms & are responsible for allergy
• Th17 regulate immunity to extracellular bacteria anf fungi
• Treg are inhibitory in terminating immune responses and inhibiting autoimmunity
• Tfh regulate humoral immunity (B cells and antibodies)

Question 13

What do the differentiating IL-12 cytokine produce ?

Answer 13

• Transcription factor = T-bet

- Produces the IFN-γ and favours the differentiation of T helper 1

Question 14

What do the differentiating IL-4 cytokine produce ?

Answer 14

• Transcription factor = GATA-3
• Produces characteristic cytokines IL-4, IL-5 and IL-13
• Produces Th2 cells

Question 15

What do the differentiating TGF-β, IL-6 and IL-23 cytokines produce?

Answer 15

• Transcription factor = RORγ
• Produces characteristic cytokines IL-17 and IL-22
• Produces Th17 cells

Question 16

What does only the IL-6 cytokine produce ?

Answer 16

• Transcription factor = Bcl-6
• Produces characteristic cytokines IL-21
• Produces Tfh cells

Question 17

What do the TGF-β and IL-2 cytokines produce ?

Answer 17

• Transcription factor = FoxP3
• Produces characteristic cytokines TGF-β and IL-10
• iTreg cells

Question 18

What is the major actions of CD4+ T helper 1 cells ?

Answer 18

• Activate specialised killing mechanisms of macrophages

- Support CD8+ T cell response

Question 19

What types of infection do CD4+ T helper 1 cells target ?

Answer 19

• Extracellular bacteria & microbes that persist in macrophage vesicles (e.g. Listeria, mycobacteria,
  Leishmania donovani, Pneumocystis carinii)
• Must be tightly regulated to avoid tissue damage

Question 20

Chronic activation of
macrophages by Th1 cells
mediates formation of ?

Answer 20

Granulomas to contain pathogens e.g. M. tuberculosis

Question 21

What is the major actions of CD4+ T helper 2 cells ?

Answer 21

• Promote enhanced barrier function & mediate contraction
  of smooth muscle(IL-13)
• Activate & recruit eosinophils (IL-5)
• Activate & recruit basophils & mast cells (IL-4).
• Induce antibody class switching to IgE (IL-4)

Question 22

What types of infection do CD4+ T helper 2 cells target?

Answer 22

Helminths parasites, allergy

Question 23

What is the major actions of CD4+ T helper 17 cells ?

Answer 23

• Activate barrier epithelial cells to upregulate anti-microbial peptides
• Recruit neutrophils

Question 24

What types of infection do CD4+ T helper 2 cells target?

Answer 24

Extracellular bacteria (e.g., Klebsiella pneumoniae), Fungi (Candida Albicans)

Question 25

What is the major actions of CD4+ T follicular helper cells?

Answer 25

• Traffic to B cell areas of lymph node & form cognate interactions with
  naive B cells through linked recognition of antigen
• Promote germinal center formation facilitating isotype switching, and affinity maturation

Question 26

What is the major actions of CD4+ T regulatory cells?

Answer 26

Generally suppress T cells & innate immune cell activity

Question 27

What types of infection do CD4+ T regulatory cells?

Answer 27

• Promote tolerance to, rather than clearance of, the antigens they recognise
• Prevent development of autoimmunity

Question 28

What does T cell plasticity allow ?

Answer 28

Effector cells to adapt to the nature/stage of response

Question 29

Give an example of this T cell plasticity ?

Answer 29

• Salmonella response begins with Th17 cells.
• Bacteria evade response by hiding within macrophages.
• This necessitates the Th17 response to evolve into Th1
  response

Question 30

What signals induce memory cell commitment?

Answer 30

Unclear but the more proliferation induced the better the memory response

Question 31

Do memory cells reflect the heterogeneity of effector cells from a primary response?

Answer 31

Unclear—memory cell response appears diverse