Natural Killer Cells Flashcards
Natural Killer cells are part of the ________ immunity
Innate
NK cells are the only ________ in the ________ immunity
Lymphocyte
Innate
Describe NK cells:
- Large granular lymphocytes
- Account for 5-15% of mononuclear cells in the blood
- Are CD3-, CD56+
90% of NK cells express _____ amounts of CD56, these are called _____________. 10% of NK cells express _____ amounts of CD56, these are called ______________.
Low amounts
CD56dim cells
High amounts
CD56bright cells
CD56dim cells are ________________ to target cells
Highly cytotoxic
CD56bright cells produce a lot of ___________
Cytokines
What is the function of NK cells?
They lyse infected or abnormal cells without prior sensitisation. They also produce a wide range of cytokines that shape the adaptive immune response.
NK cells are involved in the __________ and __________ of dendritic cells
Polarisation and maturation
NK cells can stimulate and inhibit ________________.
Haematopoiesis
NK cells are cytotoxic, they contain ________________ in their cytoplasm that contain _________ and ________
Pre-packaged granules
Perforin and Granzymes
What is perforin?
An enzyme that forms holes in the cell membrane of a target cell
What are granzymes?
Serine proteases that activate apoptosis and thus kill the cell
NK cells produce a range of ________ that help shape the immune response. i.e. ___________ and __________
Cytokines
Interferon γ (IFN-γ) and Tumour Necrosis Factor α (TNF-α)
Explain how NK cells know which cells to kill:
- NK cell inhibitory receptors bind to MHC 1 which is found on all normal cells
- Other ligands are bound by the activation receptor
- If MHC 1 is not present the cell is lysed
- In cancerous or infected cells MHC 1 is down regulated therefore NK cells kill them
Inhibitory receptors on NK cells all have the ___________________________________________
Immunoreceptor Tyrosine Inhibition Motif (ITIM)
ITIMs are ___________, when activated they recruit _____________ to counteract activation.
Phosphorylated
Phosphatases
Most Activating receptors on NK cells have the _____________________________________________
Immunoreceptor Tyrosine Activation Motif (ITAM)
The major family of NK cell receptors are _________________________________
Killer Immunoglobulin-like Receptor (KIR)
KIR consist of 2 or 3 ___________________, Inhibitory KIR have ____________ and Activating KIR have _____________
Immunoglobulin domains
Long cytoplasmic domain
Short cytoplasmic domain
C-Type Lectin family of receptors are encoded on _____________ and can be both __________ and ___________
Chromosome 12
Inhibitory and Activating
NKG2D is an _________ receptor that is importantly involved in _______________. It recognises _______________
Activating
Tumour recognition
Stress induced molecules
Natural Cytotoxicity Receptors are all __________ receptors. The main ones are __________________ an they belong to the _____________ family. They recognise a ______ range of ________.
Activating
NKp30, NKp44 and NKp46
Immunoglobulin
Wide range of Ligands
CD16 is an important receptor that is express on __________ NK cells. It recognises ________________ and mediates _________________________________
Nearly All
Antibody coated targets
Antibody Dependent Cellular Cytotoxicity (ADCC)
NK cells can also be activated by ___________ and ___________
Chemokines and Cytokines
Briefly describe NK cell development:
- Develop from a lymphoid progenitor in the bone marrow
- Migrate to the lymphnodes and mature
- Move into the Blood
CD56bright cells are ________ responsive to cytokines and they are _______ cytotoxic and _______ proliferative
Very responsive
Weakly Cytotoxic
Highly proliferative
CD56dim cells are ________ responsive to cytokines and they are _______ cytotoxic and _______ proliferative
Not very
Highly Cytotoxic
Weakly Proliferative
_______ is a marker that indicates a fully developed NK cell
CD57+
Memory NK cells have _________ function are _____ lived and _________ in response to recurrence of antigen
Enhanced function
Long Lived
Proliferate in response
What is NK cell education?
The acquisition of function through the engagement of inhibitory receptors with self
To prevent autoreactivity NK cells must be ___________
Switched on
How are NK “educated”?
- If they have the correct inhibitory receptor they are allowed to develop normally
- If they have the wrong inhibitory receptor then they don’t develop
- If they have no inhibitory receptor then they don’t develop
Cytomegalovirus (CMV) is usually ____________, it can cause _____________ in _________________________
Asymptomatic
Serious disease
Immunocompromised people
CMV causes down regulation of __________ but up regulates __________ of it to prevent NK cell attacks. It also down regulates _______ produced during _______.
HLA 1
Homolgoues
Ligands produced during Cell Stress like infection
By coating tumour cells in ________ NK cells will mediate the ______ response and kill them
Antibody
Antibody Dependent Cellular Cytotoxicity (ADCC) response
