NK Cells Flashcards
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
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
Evolutionarily, NK cells appear before ____________.
adaptive immunity
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
NK cells kill ________ infected by __________, thus eliminating reservoirs of infection
- host cells
- intracellular microbes
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
What is the abundance of NK cells?
Blood concentration is low
relative to other lymphocytes (≤10%)
What is the immunophenotype of NK cells?
- CD16Pos
- CD56Pos
- CD2Pos
- CD3Neg
What are the two cell markers used to identify NK cells?
- Anti CD-16
- Anti CD-56
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
MHC Recognition:
Unlike T cells, NK cells do not require MHC to kill target cells
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
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
Effector Molecules:
- Use Granzyme and Perforin to kill target cells
- Produces the cytokine IFNγ
Describe how granzyme and perforin are released:
- In the absence of
inhibitory receptor engagement and ligation of the activating receptor:- NK cells form tight adhesions (“conjugates”) with their target cells
-
Release (“exocytose”) granzyme and
perforin‐containing granule contents toward the target cell. - Granule contents are taken into the target cell by receptor-mediated
endocytosis, andgranzymes are released into the cytoplasm by a perforin‐dependent mechanism - Granzymes then induce apoptosis