NK Cells

Question 1

NK cells are considered **“innate” **because:

Answer 1

• Dependent on activating receptors that are germline‐encoded
  
  • as opposed to generated by VDJ recombination
• Not dependent on previous antigen exposure

Question 2

NK cells are considered “lymphocytes” because:

Answer 2

• Similar to TH cells in their ability to produce IFNγ
• Similar to CTLs in their use of perforin and granzyme

Question 3

Evolutionarily, NK cells appear before ____________.

Answer 3

adaptive immunity

Question 4

How are NK cells defined?

Answer 4

a class of lymphocytes that recognize infected and stressed cells and respond by killing these cells and secreting the macrophage‐activating cytokine IFNγ

Question 5

NK cells kill ________ infected by __________, thus eliminating reservoirs of infection

Answer 5

• host cells
• intracellular microbes

Question 6

NK cells respond to __________ produced by macrophages and secrete__________, which activates the macrophages to kill ______________.

Answer 6

• interleukin‐12 (IL‐12)
• interferon‐γ (IFN‐γ)
• phagocytosed microbes

Question 7

What is the abundance of NK cells?

Answer 7

Blood concentration is low
relative to other lymphocytes (≤10%)

Question 8

What is the immunophenotype of NK cells?

Answer 8

• CD16^Pos
• CD56^Pos
• CD2^Pos
• CD3^Neg

Question 9

What are the two cell markers used to identify NK cells?

Answer 9

• Anti CD-16
• Anti CD-56

Question 10

How does the immunophenotype reflect that NK cells are “innate” and “lymphocytes”?

Answer 10

• Neutrophils, monocytes and macrophages all express: Anti-CD-16
• CTLs and Th cells express: Anti-CD-56
• NK cells express both

Question 11

MHC Recognition:

Answer 11

Unlike T cells, NK cells do not require MHC to kill target cells

Question 12

What inhibits NK cells killing?

Answer 12

• Self class I MHC molecules are recognized by inhibitory receptors
  
  • Healthy host cells express these receptors
  • This ensures that NK cells do not attack normal host cells
  • Note: This is regardless of whether normal host cells express or do not express activating ligands for activating receptors

Question 13

What activates NK cells killing?

Answer 13

• Activated by infected cells in which ligands for activating receptors are expressed (often at high levels)
• Class I MHC expression is reduced so that the inhibitory receptors are not engaged
  
  • The result is that the infected cells are killed

Question 14

Effector Molecules:

Answer 14

• Use Granzyme and Perforin to kill target cells
• Produces the cytokine IFNγ

Question 15

Describe how granzyme and perforin are released:

Answer 15

1. In the absence of
   inhibitory receptor engagement and ligation of the activating receptor:
   
   • NK cells form tight adhesions (“conjugates”) with their target cells
2. Release (“exocytose”) granzyme and
   perforin‐containing granule contents toward the target cell.
3. Granule contents are taken into the target cell by receptor-mediated
   endocytosis, andgranzymes are released into the cytoplasm by a perforin‐dependent mechanism
4. Granzymes then induce apoptosis

Question 16

What are the target cells for NK cells?

Answer 16

• virus-infected
• tumor cells

Question 17

What would you expect to find if one were depleted of NK cells?

Answer 17

• decreased control of viral infections
• decreased control of tumor cell apoptosis
  
  • i.e. more prone to tumor development
• decreased survival rates

Question 18

What happened when HeLa cells were treated with NK cells? Why?

Answer 18

Since HeLa cells are large, flat tumor cells, they began to die.

Question 19

NK cells are the principal mediator of ________________.

Answer 19

antibodydependent cellular cytotoxicity (ADCC)

Question 20

Describe how NK cells mediate ADCC:

Answer 20

• Antibodies of certain immunoglobulin G (IgG) subclasses bind to cells
  
  • e.g. infected cells
• Fc regions of the bound antibodies are recognized by an Fcγ receptor on natural killer (NK) cells
• NK cells are activated and kill the antibody‐coated cells