NK cells Flashcards
NK cells originate from
bone marrow
how long do NK cells live for
about one week
Where are NK cells found
- blood
- spleen
- liver
when do NK cell migrate to tissues in large numbers
-only when an inflammatory reaction is underway
what type of receptors does the NK cells not posses
NK cells do not posses receptors generated through gene segment rearrangement
-(i.e. no receptors such as TCR or BCR)
what three types of cell trafficking receptors are on NK cells
- Chemotactic receptors
- Cytokine receptors
- Adhesion receptors
NK cells aka
Large granular lymphocytes (LGL)
why are NK cells referred to as LGL
-because morphologically thy resemble large lymphocytes and contain granules
how are NK cells ID in vitro in mice and humans
-by the expression of DD56, CD16, and lack of CD3
how are NK cells ID in vitro in pigs
there is no exclusive marker but CD2+/CD8+/CD3- are used with (NKp46)
how are NK cells ID in vitro in cattle
-CD335 (NKp46) has recently been reported to be expressed on bovine NK cells (horses too)
Role of NK cells in innate immunity
- Kill abnormal cells
- production of cytokine and chemokines
Following activation in vitro with cytokines such as _____ and _____ NK cells become _____________
- IL-2
- IFNy
- Lymphokine activated killer cells (LAK)
what cytokine and chemokine production are NK cells responsible for
-IFNy
-TNFalpha
-IL-17
-IL-22
-MIP-1alpha
MIP-1beta
what are abnormal cells
-cells that have become stressed by any means, infected, or a transformed cell (tumor)
How do NK cells recognize abnormal cells
-cells that are stressed, infected or transformed alter expression of certain cell surface markers
what do all normal cell express on their surface
-MHC class 1-Major histocompatibility complex class 1
how is the expression of MHC 1 affected in abnormal cells
the expression of MHC 1 is suppressed in abnormal cells
what surface markers are highly expressed on cells that are abnormal
- MHC 1 chain-related A (MICA)
- MICB
- Rae-1
- H60
what 2 types of receptors are expressed on NK cells
- Activating receptors
- Inhibitory receptors
how is the activation of NK cells regulated
-by a balance between signals from activating and inhibitory receptors
what will a high level of activating signals lead the NK cell to do
kill the target cell
what is the result of a strong inhibitory signal on the NK cell
preserves the target cell
what is an example of a strong inhibitory signal for NK cells
-Normal MHC 1 expression and absence of stress markers
when both signals for activation and inhibition are presented to the NK cell which signal is dominant
the dominant signal is the inhibitory signal
NK cell receptors are used to
recognize normal or abnormal cells
what are the two classes of receptors
- immunoglobulin-like receptors
- leptin like receptors
how does the class of receptors varry
the class of receptors vary based on the species
in Human/cattle/cats/dogs/pigs NK cell receptors that recognize the MHC 1 molecule belong to the
- Killer cell immunoglobulin-like receptor family
- AKA KIRs (or CD158)
In mice/rats/horse NK cells that recognize MHC 1 are called
- Killer cell lectin like receptors
- AKA KLRs
what type of transmembrane protein are KIRs
Type 1 transmembrane protein
T/F KIRs are not polymorphicc
F: KIRs are highly polymorphic
what are the other members the receptor family with KIRs
- LILRs (leuckocyte immunoglobulin-like receptors)
- NKp46
KIRs are expressed on _____ and subsets of ______
- NK cells
- Lymphocytes
LILRs are expressed on ______ and several types of _______
- NK cells
- Leukocytes
NKp46 is expressed on
NKp46 is expressed solely on NK cells
what type of receptors do the KIR and LILR families of receptors contain
-they contian both activating and inhibitory receptors
how is the expression of KIRs and KLRs related to Ly49
- it is mutually exclusive
- but is also expressed in humans
- non-functional
NKG2D receptor is an _____ family and is an _________ receptor
- KLRs
- activating receptor
which surface proteins does NKG2D on NK cell recognize
- it recognizes stress proteins such as MICA, MICB or ULBP (human), Rae-1, Mult1, and H60(mice)
how does the high expression of stress proteins that bind with NKG2d affect the MHC 1 inhibitory signals
-the stress signals that bind to the NKG2D override the inhibitory signal of MHC 1 and permits NK cell cytotoxicity
where else is NKG2D also expressed
-on activated y(gamma) T cells
The reduction of MHC 1 expression leaves the cell vulnerable to
destruction by NK cells
what are the effector functions of NK cells
- Lysis of infected, stressed or transformed cells
- Activation of macrophages through secretion of cytokines
what are the three mechanisms that NK cells use for cytotoxicity
- Perforin-dependent mechanism
- CD95/CD95L (Fas/FasL) mechanism
- CD16 killing pathway (ADCC)
ADCC:
Antibody dependent cellular cytotoxicity
what are the steps of the perforin dependent mechanism
1) NK cell releases perforin from its granules
2) perforin then creates a lesion in the target cell membrane - perforin channels
3) later granulysin, NK-lysin (granzymes) and fragmentin (protease) are released from cytotoxic granules and passed into perforin channels
4) Granzymes and the protease induce apoptosis of the target cell
what are the steps associated with the CD95/CD95L (Fas/FasL) mechanism
1) NK cells normally express CD95L (FasL) on the cell surface
2) target cell (abnormal cell) may have increased expression of CD95 (FAS)
3) binding of CD95L on the NK cell to CD95 on the target cell induces apoptosis of the target cell
what are the steps associated with CD16 killing pathway (ADCC)
1) NK cells also recognize target cells through an antibody dependent pathway using CD16
2) CD16 is an Fc receptor (FcyIII) expressed on NK cells
3) antibodies bind to an antigen on an infected cell, NK cells bind to antibodies through CD16 leading to NK cell cytotoxicity
when can target recognition through CD16 take place?
only when antibodies are present
NK cells are activated by cytokines such as
- IL-1
- IL-2
- IL-12
- !L-15
- IL-18
- IL-21
- type 1 IFNs
- Type 2 IFNs
treatment of the NK cells with the activating cytokines mentioned in pervious questions leads to
-LAK: lymphokine activated killer cells
What is important about LAK
they have an increased cytotoxic capacity
How can LAK be used in treatments?
-due to their highly cytotoxic characteristic they are a potential tool in immunotherapy of tumors
are there viruses that can inhibit NK cell cytotoxicity?
yes such as foot-and-mouth virus in swine
NK cells produce substantial amounts of ______ which enhances macrophage phagocytic activity
-IFN-y
NKT:
Natural killer T cells
NKT cells have properties that are similar to _______ and ________
- NK cells
- T lymphocytes
where do NKT originate from
- tymic origin
- same lineage as T cells
NKT specificity is directed against
only a few pathogens
NKT make up at least ____ to _____ of the peripheral blood mononuclear cells
0.5%-1%
what T cell receptor do NKT cells express
-an invariant alpha/beta TCR
what is the main KLR family of receptor that is expressed by NKT
NK1.1
T/F NKT cells are mostly CD4+ cells or may be double negative (CD4-/CD8-)
T
What do NKT cells mostly recognize on bacteria
-Glycolipid antigens
what activated NKT cells
IL-15
do NKT cells develop into memory cells
no
what two systems does the NKT cells link
- T cell
- NK cells
NKT cells play a role in what 4 immune responses
- allergies
- antitumor immunity
- autoimmunity
- antimicrobial immunity
NK DCs
Natural killer dendritic cells
what are NKDCs
dendritic cells that shre some properties with NK cells
what NK marker do NKDC cells express
NK1.1
what DC marker do NKDC cells express
CD11c
where are NKDCs found
- spleen
- liver
- lymph nodes
- thymus
what is the function of NKDC cells
they spontaniously lyse tumor cells
NKDC cells can present antigens to what type of cells
-naive T cells
NKDC produce large amounts of IFN-y upon stimulation through
TLR9 (CpG)
What immune systems does NKDC cells link
-innate and adaptive immunity
