Flashcards
Natural Killer Cells
Cards in this deck (24)
- 1Where do NK cells develop?Development starts in bone marrow and continues in secondary lymphoid organs (tonsils, lymph nodes)
IL-15 from antigen presenting cell (dendritic cells and CD56) required for development - 2How are NK cells restricted?MHC class I/MHC class I-like molecules restricted
- 3What markers do NK cells have?CD3-
CD56+ (isoform neural adhesion factor)
NKp46+ (natural cytotoxicity factor) (not specific to NK cells)
No simple marker - 4What is the function of IL-21?Induces the maturation of human CD34+ cells (stem cells) into NK cells
- 5What subset of NK cells represents the majority of NK cells?CD56dimCD16bright population predominant in peripheral blood, 90% of NK cells
- 6Where are CD56bright NK cells predominantly found?Lymphoid tissue/tissue cells
- 7What could the heterologous population of NK cells represent?- specific roles
- stages in NK development
- depend on local environment conditions - 8What are the two main roles of NK cells?- secrete cytokines/chemokines and influence the immune response
- kill infected/transformed cells - 9How is the activity of NK cells different to the activity of cytotoxic T cells?- cytoplasm has granules constitutively expressed whereas Tc cells need to be stimulated before they express granules
- interact with infected (virus)/malignant (cancer) cells which have reduced expression of MHC class I molecules
- can only kill the host's cells not a pathogen directly - 10What method of activation to NK cells undergo?Opposing Signal
- 11Describe the opposing signal method of activationPositive and negative regulators and the balance of stimulation of activation receptors and inhibitory receptors determines whether they are activated
- 12What are NK-22 cells, what is their function and how are they stimulated?A subset of NK cells that specialise in the production of IL-22
Described in mucosal-associated lymphoid tissue which may have memory
Triggered by acute exposure to IL-23
NK-22 cells stimulate epithelial cells to secrete IL-10, proliferate and express a variety of mitogenic and anti-apoptotic molecules - 13What is activation signalling in NK cells?Activation receptors
EG natural cytotoxicity receptors, imunoglobulin killer receptors (KIR) - 14What is inhibition signalling in NK cell activation?Inhibitory immunoglobulin killer receptors (KIR) are important as they recognise class Ia (HLA-A, B, C) ligands and/or non-classical class I ligands (HLA-E)
- 15How are cytokines involved in NK cell activation?IL-2, IL-12, IL-15, IL-18, IL-21, IFN alpha/beta
Can induce cell proliferation, NK induced cytotoxicity and/or production of IFN-gamma - 16What is an immunological synapse?Close contact between cells
- 17What are nectins/nectin-like molecules? Where are they expressed and what is their function?Belong to immunoglobulin superfamily
Expressed on epithelial cells and help to form junctions between cells
Highly expressed on tumour cells, become accessible when the structure of epithelium is disrupted
If signal is strong it can result in cell cytotoxicity - 18What are the steps in granule release?- may rely on two signals
- interaction of LFA-1 and ICAM-1 results in granule polarisation
-CD16 interaction with Fc receptor of IgG results in degranulation (stimulates antibody dependent cell-mediated cytotoxicity (ADCC))
- need co-engagement of both receptors before granules are released
- interaction of other receptors with ligands may also result in cell killing
- activation similar to CTL cells (involves perforin and caspase 3 activation) it induces apoptosis of cell target - 19How do cytokines influence the outcome?- short term NK exposure to IL-12 causes NK cells to release lots of IFN gamma and TNF alpha and high cytotoxicity activity (effector Nk cells) in lymph nodes; promote the Th1 response
- exposure to IL-18 (from dendritic cells) promotes development of CD5+/CD83+/CCR7+/CD25+ cells (helper NK cells), migratory NK cells, favour Th1 response - 20What are the three main types of NK receptors?- killer immunoglobulin-like receptor (KIR)
- Heterodimeric C-lectin receptors (CD94&NG2)
- natural cytotoxicity receptors - 21Describe KIRs- exist as paired inhibitory/activating receptors
- recognise HLA A, B, and C molecules in humans
- not a KIR for every HLA type, recognise a group of molecules
- what is recognised by each receptor not yet defined in some cases - 22Describe heterodimeric c-lectin receptorsMade from CD94 covalently linked to a product of the NG2 gene
CD94/NG2a inhibitory
Recognise non-classical MHC class 1 molecules - 23Describe natural cytotoxicity receptors- used in killing of tumour cells
- humanNK cells kill DC by activation of the calcium-calmodulin kinase II triggered by engagement of LFA I (adhesin molecule) resulting in granulation
- block with specific inhibitor of calcium-calmodulin kinase II
- only activated NK cells can kill DC (eg during viral infection)
- also activated by engagement of the phosphatidylinositol 3-kinase, ligation of NK cytotoxicity receptors NKp30 and NKp46 - 24Describe effector NK cells targeting DC cells- high expression of NKp30 & NKp46 called NKp30+NKp46+NK bright clones
- can be mediated by CD226 and NKp30 can also be involved
- suggested that NK-mediated killing may check quality and quantity of DC (DC editing)
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- 3 BM325 Flashcards on Natural Killer Cells, created by Caitlin M on 03/11/2017.
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- Caitlin M
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