Block 3- NK cells TOKA Flashcards
Where do NK cells originate from?
Bone marrow
What is the lifespan of NK cells?
~ 1 week
Where can NK cells normally be found?
Blood, spleen, and liver
What happens to NK cells when an inflammatory reaction is underway?
NK cells migrate to tissues in large #’s to the site of inflammation
True or False: NK cells have antigen receptors generated through gene segment rearrangement
FALSE. NK cells do not have antigen receptors
Does not possess receptors generated through gene segment rearrangement
What are chemotactic receptors and how do they affect NK cells?
CCR etc
Allows NK cells to move from one area to another
What are cytokine receptors and how do they affect NK cells?
IL-1R, etc
Activates NK cells
What are adhesion receptors and how to they work with NK cells?
CD2, CNAM-1, B1 integrins, B2 integrins
Helps NK cells to adhere to the endothelium of blood vessels and exit to get to site of inflammation
What are the cell trafficking receptors on NK cells?
Chemotactic, cytokine, and adhesion receptors
What is the morphology of NK cells?
Referred to as Large Granular Lymphocytes (LGL)
they contain granules that contain molecules for cytotoxicity
Lytic granules kill virus infected cells
What is the role of NK cells in innate immunity?
- Kills/lysis of VIRUS-INFECTED, TUMOR, and STRESSED cells
- Produce cytokines and chemokines that help regulate other cells
- Activate macrophages through secretion of cytokines
- Also can help control hematopoiesis
What is an “abnormal cell” ?
A cell that is
- stressed
- infected
- or has an altered expression of certain cell surface markers
What do all normal, nucleated cells express on their cell surface?
MHC1
What happens to the cell surface in virus or tumor infected cells?
MHC1 is supressed or failed to express
Infected cells express stress proteins instead that can be recognized by NK cells
What are MICA and MICB?
stress proteins that are highly expressed on the surface of stressed cells
alerts NK cells to kill
What type of recognition receptors do NK cells express?
- Activating receptors
- Inhibitory receptors
How do NK cells recognize abnormal cells?
Using Activating and Inhibitory Nk cell receptors
What happens if a high level of activating signals are expressed?
Activated NK cell to kill target cell
this happens when no MHC1 is found on target cell
What happens if there is a strong inhibitory signal?
NK cells will preserve the cell instead of kill
this happens when a normal MHC1 is expressed on the target cell and there are no stress markers
What is the dominating NK receptor and how does it work?
Inhibitory receptor dominates and blocks activating signal
this helps prevent NK cells from killing normal cells
What are some activating receptors on NK cells?
NKp46
CD16
NKG2D
What do inhibitory receptors on NK cells do?
They recognize MHC1 molecules expressed on normal cells and preserve them instead of kill them
What happens in there is a reduction of lack of MHC1 expression on a cell?
renders a cell vulnerable to destruction by NK cells
What are some inhibitory receptors on NK cells?
CD94/NKG2A
How do NK cells and macrophages work together?
- Macrophage releases IL-12
- IL-12 activated NK cell
- Activated NK cell secretes IFN-y
- IFN-y increases macrophage ability to phagocytose microbes
What the mechanisms for NK cell cytotoxicity/killing? and what is the end result?
- Perforin-dependent mechanism
- CD95/CD95L (Fas/FasL) mechanism
- CD16 killing pathway (ADCC-Antibody dependent cellular cytotoxicity)
End result of all 3 pathways are APOPTOSIS
Explain the perforin-dependent mechanism of the NK cell
When activating and stress molecules bind to NK cells it triggers the release of PERFORIN contained in the granules
PERFORIN creates a lesion in the target cell membrane and makes a perforin channel
Perforin channel triggers release of GRANULYSIN, NK-LYSIN and FRAGMENTIN (protease) to be released from NK cell
These granzymes pass through the perforin membrane and induce APOPTOSIS
What enzymes are contained in the granules of NK cells?
- Perforin
- Granulysin
- NK lysin
- Fragmentin (protease)
Explain the CD95/CD95L (Fas/FasL) mechanism of the NK cell
NK cells normally express CD95L (FasL) on the cell surface
- Target cells show an increased expression of CD95 (Fas)
- CD95L on NK cell surface recognizes and binds to CD95 on the target cell which induces APOPTOSIS
Explain the CD16 (ADCC) killing pathway in NK cells
CD16 acts as a Fc receptor on NK cells
This pathway only occurs when antibodies are present
When antibodies are present they bind to an antigen on the infected cell
This alerts the CD16 (Fc) receptor on NK cells to bind to the antibody which is bound to the antigen and induces APOPTOSIS
Antibody kinda acts like opsonization to alert the NK cell to come kill
What are Lymphokine activated killer cells (LAK)?
when isolated NK cells are mixed with cytokines IN VITRO they lead to LAKs that have an increased cytotoxic capacity
highly cytotoxic cells
used in immunotherapy of tumors
What is the relevance of foot and mouth disease in swine to NK cells?
This virus INHIBITS NK cell cytotoxicity instead of enhances its ability to kill
So this tends to be deadly virus in swine
Where do NKT cells originate from?
Same lineage as T cells, thymic origin
What are some functions of NKT cells?
makes up 1% of the peripheral blood mononuclear cells
specifically directed against only few pathogens
does not develop memory
links T cells to NK cells
plays a role in ALLERGIES, ANTI-TUMOR immunity, AUTOIMMUNITY, and ANTIMICROBIAL immunity
CD4+ or CD4- CD8-
How are NKT cells activated?
by IL-15
What do NKT cells express?
a/B TCRs
NK1.1 receptors
KCR family receptors
What do most NKT cells recognize?
glycolipid antigens on bacteria
What do NK DCs express?
NK1.1
CD11c
Where are NK DCs found?
Spleen, liver, lymphnodes, and thymus
What is the function of NK DC cells?
- Lyse tumor cells
- Present antigens to naive T cells
- Produce IFNy upon stimulation through TLR9
- Link the innate and adaptive immunity
