Natural Killer Cells Flashcards
Natural killer cells originate from the ____ _____ and can be found in the ____, ____, and _____.
Natural killer cells originate from the BONE MARROW and can be found in the BLOOD, SPEEN, and LIVER.
When do NK cells migrate to tissue in large numbers?
During an inflammatory reaction
Natural Killer cells are also known as
Large granular lymphocytes
Abnormal cells that NK cells kill
Stressed
Infected
Tumor
Following activation in vitro with cytokines such as IL-2 and IFNy, NK cells become _____ ____ killer cells.
Lymphokine activated killer cells (LAK)
All normal cells in the body express _____ on their surface.
MHC I molecules
In infected cells, MHC I molecules expression is ____.
suppressed
What kind of abnormal cells often fail to express MHC I molecules on their surface?
tumor cells
On the surface of stressed cells, _____ and _____ are highly expressed.
MICA and MICB
*MHC I chain-related A and B
Activation of NK cells is regulated by a balance between signals from _____ and _____ receptors.
Activating and inhibitory
What does a high level of activating signals result in?
NK cell killing target
What does a high level of inhibitory signals result in?
Preserves the cell. Normal MHC I expression and lack of stress markers.
Generally, _____ signals are usually blocked by ______ signals to prevent killing of normal cells.
Generally, ACTIVATING signals are usually blocked by INHIBITORY signals to prevent killing of normal cells.
In humans, cattle, cats, dogs and pigs, NK cell receptors that recognize MHC I belong to the _____ family.
KIR (killer cell immunoglobulin-like receptor)
*expressed on NK cells and some lymphocytes
In mice, rats and horses, NK cell receptors that recognize MHC I belong to the ______ family.
KLR (killer cell lectin-like receptor)
2 classes of KIRs
LILRs (leukocyte immunoglobulin-like receptors) - expressed on NK cells and some leukocytes
NKp46 - expressed only on NK cells
What is the activating receptor for KLRs that recognizes stress proteins (MICA or MICB)?
NKG2D receptor
High expression of stress proteins allows binding of ____, which overrides the inhibitory signals through MHC I and permits NK cell toxicity.
NKG2D
3 important activating receptors on NK cells that bind to ligands on stressed, infected, or tumor (transformed) cells.
NKp46
CD16
NKG2D
By forcing NK cells to express increased amounts of NKG2D in vitro, what effect is proposed on the body?
Increased expression should lead to overriding of inhibitory signals and allow NK cells to kill tumor cells.
CD94 (NKG2A) inhibitory receptors can be blocked using an antibody to have what effect?
Will allow NK cells to override MHC I inhibitory signals on cancer cells and kill them
In addition to lysing abnormal cells, NK cells also activate ______ through the release of cytokines.
macrophages
3 NK cell cytotoxicity mechanisms
Perforin-dependent
CD95/CD95L
CD16 killing pathwy (ADCC)
In the perforin-dependent mechanism, the NK cell releases ______ from its granules, which creates a lesion in the target cell membrane.
Perforin
*perforin channels
_______ enter the target cell through perforin channels and induce apoptosis.
Granzymes (NK-lysin)
In the CD95/CD95L mechanism, when ____ on the NK cell binds _____ on the target cell, apoptosis is induced.
In the CD95/CD95L mechanism, when CD95L on the NK cell binds CD95 on the target cell, apoptosis is induced.
In the CD16 killing pathway (ADCC), NK cells recognize target cells through an ______ dependent pathway using the Fc receptor CD16.
antibody
When an Ab binds to an Ag on an infected cell, NK cells will bind to that antibody through ____, leading to NK cytotoxicity.
CD16
Cytokines that activate NK cells
IL-1 IL-2 IL-12 IL-15 IL-18 IL-21 type I and II IFNs
Lymphokine activated killer cells (LAK) are NK cells that have been treated with _____ and have increased _____ capacity.
cytokines, cytotoxic
Since LAK are highly toxic, they are a potential tool in the treatment of _____.
Cancer
Example of a virus that inhibits NK cell cytotoxicity
Foot-and-mouth disease in swine
NK cells produce ____, which enhances macrophage phagocytic activity.
IFN-y
Natural Killer T cells (NKT) are from the same lineage as _____and are mostly CD4+ cells.
T lymphocytes
NKT cells express ____ family receptors and mostly recognize _____ _____ on bacteria.
KLR
glycolipid antigens
NKT cells are activated by ____ and link the NK cells and T cell system.
IL-15
NKT cells play a role in
allergies
anti-tumor immunity
autoimmunity
antimicrobial immunity
Natural killer dentritic cells (NK DCs) spontaneously lyse ____ cells.
tumor
NK DCs link the _____ and ______ immunity.
innate and adaptive
