Adaptive immunity 2

Question 1

Describe the basics of lymphocyte activation, differentiation, memory and effector responses

Answer 1

• antigen recognition - receptor has to recognise the antigen being presented to it by APC
• if there are other stimulatory signals - T cells are activated
• this causes secretion of IL-2R cytokine (main T cell growth factor)
• acts as an autocrine loop - drives clonal expansion of antigen specific cell
• also have differentiation of the responding cell - differentiate into a particular effector cell that actively performs its funtion
• differentiate into memory cells

Question 2

What is the 2 signal hypothesis for T cell activation?

Answer 2

• co-stimulatory signals required for optimal T cell activation and proliferation
  
  • signal 1 - antigen-specific TCR engagament
  • signal 2 - contact with co-stimulatory ligands
    
    • signal 3 - cytokines directing T cell differentiation into distinct effectory cell types

Question 3

What are the positive co-stimulatory receptors that facilitate activation and proliferation? (signal 2)

Answer 3

• CD28
  
  • 44kDa glycoprotein homodimer - expressed on majority of T cells
  • binds to CD80 and CD86 expressed by APCs
  • initial activation events
• ICOS
  
  • inducible co-stimulator
  • binds ICO-ligand on activated APCs
  • expressed on memory cells and effector T cells
  • help to maintain activity of already differentiated cells

Question 4

What are the negative co-stimulatory receptors (help turn activation off)

Answer 4

• CTLA-4
  
  • induced within 24 hours after after activation, peaks 2-3 days post-stimulation
  • binds to CD80/86 with higher affinity than CD28, but shuts down signaling pathways
• PD-1
  
  • programme death 1 CD279 and BTLA
    
    • PD-1 - help to mediate T cell tolerance in non-lympoid tissues
    • BTLA - down regulate inflam and autoimmune responses

Question 5

What is clonal anergy?

Answer 5

• state of non-responsiveness

Question 6

When does clonal anergy occur?

Answer 6

• if a co-stimulatory signal is absent
• helps to provide tolerance (especially in periphery)
• if only 1 signal is recieved - cell in rendered nonresponsive
• might happen if a T cell isnt screened against peripheral self-antigen during development

Question 7

In T cell activation, what do the initial signals 1 and 2 induce?

Answer 7

• up-regulation of pro-survival genes
• transcription of IL-2 and IL-2R genes
• IL-2 is an example of an autocrine type of cytokine response system
• outcome is activation and robust proliferation
  
  • production of memory and effecrot clonal cell pops

Question 8

Describe what happens during signal 3

Answer 8

• depending on which cytokines are present as the T cell becomes activated, different outcomes can occur
• cytokines can send the T cell down different subset development pathways

Question 9

What are theb CD4 T cell distinct subsets?

Answer 9

• Th1 and Th2
• Th17
• Treg
• Tfh - (follicular)

Question 10

How do PAMPs aid in T cell differentiation?

Answer 10

• PAMPs bind to PRRs on the APC
• different PPRs = different cytokines produced
  
  • viruses stimulate IL-12 to induce Th1 subsets
  • worms stimulate IL-4 to induce Yh2 subsets
• this creates the cytokine evironment that drives the T cell down a pathway
• APC detect PAMP (virus, bacteria etc)
• produce a cytokine environment that drives the helper cell to become the most appropriare population to deal with infection