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Flashcards in NK Cells Deck (20):
1

NK cells are considered  "innate"  because:

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

2

NK cells are considered "lymphocytes"  because:

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

3

Evolutionarily, NK cells appear before ____________.

adaptive immunity

4

How are NK cells defined?

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

5

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

  • host cells
  • intracellular microbes

6

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

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

7

What is the abundance of NK cells?

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

8

What is the immunophenotype of NK cells?

  • CD16Pos
  • CD56Pos 
  • CD2Pos
  • CD3Neg

9

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

  • Anti CD-16
  • Anti CD-56

10

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

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

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11

MHC Recognition: 

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

12

What inhibits NK cells killing?

  • 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 

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13

What activates NK cells killing?

  • 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

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14

Effector Molecules: 

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

15

Describe how granzyme and perforin are released:

  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
    , and granzymes are released into the cytoplasm by a perforin‐dependent mechanism 
  4. Granzymes then induce apoptosis

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16

What are the target cells for NK cells?

  • virus-infected
  • tumor cells

17

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

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

18

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

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

19

NK cells are the principal mediator of ________________.

antibodydependent cellular cytotoxicity (ADCC)

20

Describe how NK cells mediate ADCC:

  • 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