L18- Cytoxicity (2) Flashcards
What are NK cells activated by?
- IFN-a/b
- TNF-a
- IL-12
What is NK cell killing triggered by?
- FC-g RIII receptor which binds to antibody on target cell
- Lack of class I MHC molecule
- Altered self molecules
What do NK cells do?
Kill virus-infected target cells and release cytokines
Are able to deliver response immediately after recognising specific signals, do not need to develop or differentiate further (key difference)
How does ADCC work?
- Antibody binds antigens on surface of target cells
- Fc receptors on NK cells recognise bound antibody
- Cross- linking of Fc receptors signals the NK cell to kill the target cell by apoptosis
What are the NK cell receptors?
- Killer immunoglobulin like receptors (KIRS)
- C-type lectin like receptors
Can be both activating and inhibiting
What are KIRS?
- Bind MHC class I (humans only)
- KIR2D- HLAC
- KIR3D- HLAB
- Mainly signal via ITIMS and are inhibitory
What are ITIMS and ITAMS?
Immunoreceptor tyrosine based inhibitory/activating motifs
What are C-typle lectin like receptors?
- Bind non-classical MHC I (HLA-E)
* Majority signal via ITIMs and are inhibitory
What are examples of inhibitory receptors on NK cells?
- KIR2DL1
- KIR2DL2
- CD94/ NKG2A
What are examples of activating receptors on NK cells?
- NKG2D
- NKp30
- NKp44
What are the stages of NK cell lytic synapse formation?
- Initiation- establishment of close association then firm adhesion via receptor ligand interactions then synapse initiation
- Effector- actin reorganisation, f actin polymerisation, lytic granule fusion
- Termination- down modulation of activating receptors, detachment
What is an inhibitory immune synapse?
- Family of inhibitory receptors (recognise healthy self) and form and inhibitory synapse to prevent lysis- induce activity of SHP1 phosphatases
- Resting NK cells need robust mechanism to prevent inadvertent cytolysis
