Natural Killer Cells

Question 1

Natural Killer cells are part of the ________ immunity

Answer 1

Innate

Question 2

NK cells are the only ________ in the ________ immunity

Answer 2

Lymphocyte

Innate

Question 3

Describe NK cells:

Answer 3

• Large granular lymphocytes
• Account for 5-15% of mononuclear cells in the blood
• Are CD3-, CD56+

Question 4

90% of NK cells express _____ amounts of CD56, these are called _____________. 10% of NK cells express _____ amounts of CD56, these are called ______________.

Answer 4

Low amounts
CD56dim cells
High amounts
CD56bright cells

Question 5

CD56dim cells are ________________ to target cells

Answer 5

Highly cytotoxic

Question 6

CD56bright cells produce a lot of ___________

Answer 6

Cytokines

Question 7

What is the function of NK cells?

Answer 7

They lyse infected or abnormal cells without prior sensitisation. They also produce a wide range of cytokines that shape the adaptive immune response.

Question 8

NK cells are involved in the __________ and __________ of dendritic cells

Answer 8

Polarisation and maturation

Question 9

NK cells can stimulate and inhibit ________________.

Answer 9

Haematopoiesis

Question 10

NK cells are cytotoxic, they contain ________________ in their cytoplasm that contain _________ and ________

Answer 10

Pre-packaged granules

Perforin and Granzymes

Question 11

What is perforin?

Answer 11

An enzyme that forms holes in the cell membrane of a target cell

Question 12

What are granzymes?

Answer 12

Serine proteases that activate apoptosis and thus kill the cell

Question 13

NK cells produce a range of ________ that help shape the immune response. i.e. ___________ and __________

Answer 13

Cytokines

Interferon γ (IFN-γ) and Tumour Necrosis Factor α (TNF-α)

Question 14

Explain how NK cells know which cells to kill:

Answer 14

• 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

Question 15

Inhibitory receptors on NK cells all have the ___________________________________________

Answer 15

Immunoreceptor Tyrosine Inhibition Motif (ITIM)

Question 16

ITIMs are ___________, when activated they recruit _____________ to counteract activation.

Answer 16

Phosphorylated

Phosphatases

Question 17

Most Activating receptors on NK cells have the _____________________________________________

Answer 17

Immunoreceptor Tyrosine Activation Motif (ITAM)

Question 18

The major family of NK cell receptors are _________________________________

Answer 18

Killer Immunoglobulin-like Receptor (KIR)

Question 19

KIR consist of 2 or 3 ___________________, Inhibitory KIR have ____________ and Activating KIR have _____________

Answer 19

Immunoglobulin domains
Long cytoplasmic domain
Short cytoplasmic domain

Question 20

C-Type Lectin family of receptors are encoded on _____________ and can be both __________ and ___________

Answer 20

Chromosome 12

Inhibitory and Activating

Question 21

NKG2D is an _________ receptor that is importantly involved in _______________. It recognises _______________

Answer 21

Activating
Tumour recognition
Stress induced molecules

Question 22

Natural Cytotoxicity Receptors are all __________ receptors. The main ones are __________________ an they belong to the _____________ family. They recognise a ______ range of ________.

Answer 22

Activating
NKp30, NKp44 and NKp46
Immunoglobulin
Wide range of Ligands

Question 23

CD16 is an important receptor that is express on __________ NK cells. It recognises ________________ and mediates _________________________________

Answer 23

Nearly All
Antibody coated targets
Antibody Dependent Cellular Cytotoxicity (ADCC)

Question 24

NK cells can also be activated by ___________ and ___________

Answer 24

Chemokines and Cytokines

Question 25

Briefly describe NK cell development:

Answer 25

1. Develop from a lymphoid progenitor in the bone marrow
2. Migrate to the lymphnodes and mature
3. Move into the Blood

Question 26

CD56bright cells are ________ responsive to cytokines and they are _______ cytotoxic and _______ proliferative

Answer 26

Very responsive
Weakly Cytotoxic
Highly proliferative

Question 27

CD56dim cells are ________ responsive to cytokines and they are _______ cytotoxic and _______ proliferative

Answer 27

Not very
Highly Cytotoxic
Weakly Proliferative

Question 28

_______ is a marker that indicates a fully developed NK cell

Answer 28

CD57+

Question 29

Memory NK cells have _________ function are _____ lived and _________ in response to recurrence of antigen

Answer 29

Enhanced function
Long Lived
Proliferate in response

Question 30

What is NK cell education?

Answer 30

The acquisition of function through the engagement of inhibitory receptors with self

Question 31

To prevent autoreactivity NK cells must be ___________

Answer 31

Switched on

Question 32

How are NK “educated”?

Answer 32

• 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

Question 33

Cytomegalovirus (CMV) is usually ____________, it can cause _____________ in _________________________

Answer 33

Asymptomatic
Serious disease
Immunocompromised people

Question 34

CMV causes down regulation of __________ but up regulates __________ of it to prevent NK cell attacks. It also down regulates _______ produced during _______.

Answer 34

HLA 1
Homolgoues
Ligands produced during Cell Stress like infection

Question 35

By coating tumour cells in ________ NK cells will mediate the ______ response and kill them

Answer 35

Antibody

Antibody Dependent Cellular Cytotoxicity (ADCC) response