Natural Killer Cells Flashcards
Describe natural killer cells.
-originate in bone marrow
-found in blood, spleen, liver
-migrate to diff tissue via chemotatic, cytokine, & adhesion receptors during inflammatory response = activated
-dont have receptors made through gene segment rearrangement
-‘lg granular lymphocyte’
-lytic granules kill infected/tumor cells
Describe the role of NK cells in innate immunity.
- Kill virus infected, tumor, stressed cells
-activation in vitro via cytokines like IL2 & IFNy = become lymphokine activated killer cells (LAK) *NOT FOUND IN VIVO (BODY) - Cytokine & chemokine production: IFNy & TNFs & IL
-activates macrophages
Describe a normal cell VS abnormal cell.
-normal cell surface markers present = express self MHC I
-abnormal cells dont express MHC I
>express MHC I chain related A (MICA & MICB), rae1, H60
How do NK cells recognize abnormal cells?
2 types of recog receptors:
1. Activating = kill abnormals
2. Inhibitory = dont kill normals
*activating signals blocked by inhibitory signs to prevent killing of normal cells
Describe NK cell receptor differences in species.
- Immunoglobulin like receptors
-humans, cattle, dog, cat, pig
-NK cell receptor recog MHC I = killer cell immunoglobulin-like receptor (KIRs) - Lectin like receptors
-mice, rats, horses
-NK cell receptors recog MHC I = killer cell lectin like receptors (KLRs)
Describe KIRs.
-type 1 transmembrane proteins
-polymorphic
-includes leukocyte immunoglobulin like receptors (LILRs) = expressed on NK cells & leukocytes
-KIRs expressed on NK cells & lymphocytes
Describe KLRs.
-NKG2D receptor = expressed on activate T cells
-recognizes stress proteins like MICA, MICB
>high expression of stress proteins allows binding of NKG2D by overriding inhibitory signals through MHC I & permits NK cell cytotoxicity
Describe activating receptors on NK cells.
-bind to ligands expressed on abnormal cells
-NKG2D, CD16, NKp46 KNOW THIS
Describe inhibitory receptors on NK cells.
-CD94/NKG2A KNOW THIS
Describe NK cell cytotoxicity mechanisms.
- perforin-dependent
- CD95
- CD16 (ADCC)
Describe perforin-dependent mechanism.
-NK cell releases perforin
-perforin creates perforin channels on target cell
-granulysin, NK lysin, & fragmenetin = released from cytotoxic granules & go thru perforin channels
-granzymes & protease induce apoptosis of target cell
Describe CD95 mechanism.
-NK cells express CD95L
-target cells have CD95
-bind CD95L (NK cells) to CD95 (target cell) = apoptosis
Describe CD16 killing pathway (ADCC).
-NK cells recognize target cells = antibody dependent pathway using CD16
-CD16 = Fc receptor on NK cells
> NK cell cytotoxicity
Describe the regulation of NK cell activity.
-NK cells activated by cytokines (IL1, IL2, IL12, IL15, IL18, IL21, type I & II IFNs
-NK cells + cytokines = lymphokine activated killer cells (LAK) increased cytotoxic capacity used for cancer/tumors
-some viruses inhibit NK cell cytotoxicity
Describe NK T cells (NKT).
-similar to NK & T lymphocytes
-thymic origin
-1% of peripheral blood mononuclear
-express invariant a/B TCR
-express NK1.1 & KLR receptors
-CD4+ cells or may be double negative
-recognize glycolipid antigens on bacteria
-activated by IL15
-no memory cells
-link T cells to NK cells
-allergies, antitumor immunity, autoimmunity, & antimicrobial immunity