Chapter 12 (12.1-12.8)

Question 1

What kind of receptors are found on NK cell surface?

Answer 1

• Toll-like
• detecting infection + cellular stress
• inhibitory (to prevent killing healthy cells)
• variety cause NK cells have to perform many functions
  
  • circulate in blood half active -> respond very fast

Question 2

How is NK-cell activated during adaptive immune response?

Answer 2

• FcyRIII receptor binds to IgG with low affinity
  
  • no additional signals needed -> ADCC starts

Question 3

How can NK cell detect “missing self” and what will be the response?

Answer 3

• inhibitory receptor (CD94:NKG2A) binds to HLA-E (MHC class I molecule)
  
  • expression of HLA-E indicates levels of expression of other HLAs (if there is no E, there will be no A, B or C -> protein assembly is similar, for E narrower) = unhealthy cell
• HLA-E present -> receptor on NK will bind -> no response
• no HLA-E -> weak receptor engagement -> NK cell activated -> ADCC
• activating receptor (NKG2D) bind to MIC-A and MIC-B glycoproteins -> produced during cellular stress
  
  • also signals coming from 2B4 (engages with CD48 -> virus infection)

Question 4

What are killer-cell immunoglobulin-like receptors (KIRs)?

Answer 4

• on NK specifically to detect polymorphic determinants of HLA-A, B and C
  
  • HLAs differ in a1 helix (position 80) -> different receptors on NK cells bind different allotype of HLAs
    
    • all HLA-C allotypes are presented, some of HLA-A, -B
• unrelated to CD94:NKG2A (binding to HLA-E)

Question 5

How does the process of NK-cell education look like?

Answer 5

• immature NK cell produces inhibitory KIR recognising self-HLA-C
  
  • activating and inhibitory receptors send signals (dynamic balance)
  • balance maintained in educated NK cell in blood
• binds to healthy cell -> inhibitory signal dominates
  
  • vice versa for unhealthy cell