Brainscape's Knowledge GenomeTM


Top Flashcards (Certified)
All Flashcards

Infection and Immunity > NK cells and Gamma/Delta T cells > Flashcards

NK cells and Gamma/Delta T cells Flashcards

(99 cards)

Start Studying
1
Q

What are NK cells?

A

A subset of innate lymphoid cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What determines the phenotypic differences between ILC subsets?

A

Transcription factors
e.g. T-bet, GATA3 and RORgt

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What are the type of gd T cells?

A

Vd1 - skin, lung, gut
Vd2 - blood, lymph node, spleen
Vd3 - blood (rare)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Describe NK cells

A

Large granular lymphocytes that are not T or B cells
Do not express TCR or BCR
Do not express cell surface marker CD56
CD3- CD56+

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What do NK cells do?

A

Cytokine secretion
Cytotoxicity causing lysis of target cell

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What defines NK cell subsets?

A

CD56 expression level
10% of NK cells are CD56bright, 90% are CD56dim

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Describe CD56bright NK cells

A

Predominantly found in secondary lymphoid organs
Greater cytokine production
Low level of perforin/granzymes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Describe CD56dim NK cells

A

Low CD56 expression
Predominantly found in blood
Highly cytotoxic
High level of perforin/granzymes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What are the cytokines released by NK cells?

A

IFN-g
TNF-a

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What does IFN-g released by NK cells do?

A

Activation, growth and differentiation of T, B, NK cells and macrophages
Promotes Th1 differentiation
Enhances MHC expression on APC

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What does TNF-a released by NK cells do?

A

Inflammatory mediator
Regulates growth and differentiation of a wide variety of cells
Selectively cytotoxic for many transformed cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What do NK cells release to kill target cells?

A

Lytic granules containing proteins that act on the target cell

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What proteins do lytic granules of NK cells contain?

A

Perforin
Granzymes
Granulysin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What does perforin do?

A

Aids in delivering contents of granules into the cytoplasm of the target cell

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What are granzymes and what do they do?

A

Serine proteases
Activate apoptosis once in the cytoplasm of the target cell

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What does granulysin do?

A

Has antimicrobial actions and can induce apoptosis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Describe the role of NK cells in cancer

A

Medium and high cytolytic function of NK cells = reduced cancer risk (because NK cells are in abundance and can fight cancer cells)
Low cytolytic function = increased cancer risk
LAK cell therapy can be used for individuals with low cytolytic function

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

How do LAK cells work?

A

Lymphokine-activated killer cells
In the presence of IL-2 they are stimulated to kill tumour cells
They have many receptors/adhesion molecule on their surface for IL-2 so they are cultured to increase cell division into the cytotoxic line of cells and become activated to kill cancer cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Describe the role of NK cells in infection

A

Low NK activity = increased risk of herpesvirus infections

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

How are NK cells activated in viral infection?

A

Virus infected cells release IFN-a and IFN-b
This induces resistance to viral replication in all cells
Increase MHC-I expression and antigen presentation in all cells
Activate NK cells to kill virus infected cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

How do NK cells make the decision to kill?

A

Fc receptor recognition of Ab/Ag complexes
Balance of activating/inhibitory receptors - detection of missing self and detection of induced self

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

What is missing self?

A

When there is an absence or altered expression of MHC-I molecules
Inhibitory receptors on NK cells cannot bind to MHC-I which leads to cell lysis of the target cell

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

What is induced self?

A

When target cells express activating ligands that bind to activating receptors and result in NK cell killing
However if MHC-I present and binds to inhibitory receptor then there is balance of activating/inhibitory receptors, resulting in no killing

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

Describe antibody-dependent cell-mediated cytotoxicity (ADCC)

A

Ab bind Ags on surface of target cells
CD16 (FcgRIII) on NK cells allows them to bind to Ab-coated targets
Cross-linking of Fc receptors signals the NK cell to kill the target cell
e.g. Rituximab and CD20 in Burkitt’s lymphoma

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Describe how Rituximab causes killing of Burkitt cells
Rituximab is a monoclonal antibody Binds to CD20 on Burkitt cells CD16 on NK cells will bind to Rituximab and cause cross-linking of the Fc receptors Burkitt cells are killed
26
How to inhibitory receptors signal?
Through ITIMs
27
How do activating receptors signal?
Through ITAMs
28
What receptors regulate NK cell function?
Killer Ig-like receptors (KIR) Leukocyte Ig-like receptors (LILR) Both are encoded in the leukocyte receptor complex (LRC) on chromosome 19
29
Describe KIR
Innate immune receptors Regulate the activity of NK cells Polymorphic Individual KIR genes vary in their presence between individuals
30
Describe LILR
Innate immune receptors Regulate functions of NK cells and APCs
31
Describe how KIRs function
When KIR recognise MHC-I they inhibit NK cells from releasing lytic granules Some viruses downregulate MHC-I to evade cytotoxic T cells If a target cell does not express MHC-I then there is no KIR inhibition Lytic granules will then be released to lyse the target cell Known as missing self
32
What do inhibitory KIR bind to?
The same face of MHC-I as the TCR
33
What do the KIRs recognise?
Subsets of MHC-I alleles
34
What do different MHC-I/KIR combinations show?
Disease associations e.g. in HIV infection
35
What happens in the interaction of an NK cell with a healthy autologous cell?
No killing of healthy autologous cell
36
What happens in the interaction of an NK cell with a healthy allogeneic cell of similar HLA-C type?
No killing of allogeneic cell of similar HLA-C type
37
What happens in the interaction of an NK cell with a healthy allogeneic cell of different HLA-C type?
Killing of healthy allogeneic cell of different HLA-C type
38
Why are tumour cells susceptible to NK cells?
Tumour cells downgrade the expression of MHC-I This means inhibitory receptors on NK cells will not bind to the tumour cell Causes lysis of tumour cell
39
How are KIR receptors named?
Based on number of Ig domains Whether they have a long or short cytoplasmic tail - inhibitory receptors have long tails, activating receptors have short tails e.g. KIR3DL1 = 3 Ig domains, long cytoplasmic tail KIR2DS1 = 2 Ig domains, short cytoplasmic tail
40
What do NK cells need to become mature?
Ligation of inhibitory receptors This supposes that the inhibitory receptors play 2 opposing roles dependent on the stage of NK maturation - to license the cell and to stop cytotoxicity
41
How do inhibitory and activating receptors exist?
As heterodimers
42
What is the name of the inhibitory receptor?
CD94/NKG2A, B KIR2DL KIR3DL
43
What are the names of activating receptors?
CD94/NKG2C CD94/NKG2E KIR2DS KIR3DS
44
What do inhibitory and activating receptors recognise?
HLA-E on target cell
45
What is HLA-E?
Non-classical MHC-I protein that presents leader peptides from other MHC-I molecules (HLA-A, B, C)
46
What does HLA-E bind to?
Lectin-like receptors NKG2A, B and C NKG2A, B and C form heterodimers with CD94
47
Why do we need HLA-E?
Some immune cells can be HLA-E-restricted so HLA-E will present the peptides needed for recognition from other HLA class I allotypes CD94/NKG2A is specific to HLA-E meaning it will not bind to other HLA class I allotypes
48
What is the structure of HLA-E?
a1, 2 and 3 subunits b2m subunit
49
Describe LILRs
Encoded adjacent to KIR in the leukocyte receptor complex (LRC) They have inhibitory motifs - LILRB (inhibitory) Short tail and associate with adaptor proteins - LILRA (activatory) Varying expression profiles LILRB1 expressed by NK cells - powerful immune inhibitor
50
Describe NKG2D
Expressed on NK cells, gd T cells, CD8+ ab T cells and macrophages Associates with DAP10 for signalling Binds to MHC-I-like proteins, MICA, MICB, ULBPs Activating
51
What happens when NKG2D recognises MICA, MIC or ULBPs?
Release of perforin Release of IFN-g, TNF-a and GM-CSF
52
What inhibitory receptors recognise missing self?
KIR recognise classical MHC LILR recognise classical and non-classical MHC NKG2A, B and C recognise non-classical MHC
53
What activating receptors recognise induced self?
NKG2D recognise MICA, MICB and ULBPs
54
What are the natural cytotoxicity receptors?
NCR1, NCR2 and NCR3
55
What do NCRs do?
Provide activating signals to NK cells
56
What are the ligands for NCR1?
Viral hemagglutinin
57
What does NCR2 bind?
A ligand expressed on tumour cells and upregulated by viral (HIV) infection
58
What is the ligand for NCR3 (NKp30)?
BAT3 - a stress induced protein
59
What does target cell death or survival depend on?
Balance of activating and inhibitory signals e.g. if 3 activating ligands bind activating but only 1 MHC binds to inhibitory receptor then target cell is lysed because more activation than inhibition
60
How does cytomegalovirus (CMV) evade immune response?
Produces UL16 which binds NKG2D ligands, retaining them in the cytoplasm This prevents recognition b NK cells and co-recognition of CD8 T cells
61
How do tumours avoid immune response?
They produce soluble MIC as a decoy so that the CTLs do not bind to the membrane-bound MIC and cause lysis
62
Describe the role of HLA-G in immune invasion
Normally only expressed by trophoblast during pregnancy but is expressed by many tumours and can be upregulated in HIV infection HLA-G is the highest affinity ligand for LILRB1 LILRB1 is expressed on B cells, NK cells, T cells and APCs and can inhibit the functions of each
63
What are some other innate lymphocytes?
B1 cells Epithelial gd cells NK T cells
64
Describe B1 cells
Make natural Ab - protect against infection with Strep pneumoniae Ligands no MHC associated Cannot be boosted
65
Describe epithelial gd cells
Produce cytokines rapidly Ligands are MHC class IB associated Cannot be boosted
66
Describe NK T cells
Produce cytokines rapidly Ligands are lipids bound to CD1d Cannot be boosted
67
What is the difference between NK T cells and CD8/CD4 T cells?
NK T cells express a biased T cell receptor repertoire Most NK T cells use a particular TCR alpha chain rearrangement (Va24JaQ) in humans
68
What receptors do NK T cells express?
Some inhibitory and activation receptors - relevant in bacterial and viral infection
69
What do NK T cells do?
Kill tumour cells in vitro Produce cytokines
70
What does the NK T cell TCR recognise?
Glycolipids in the context of CD1d (MHC I-like molecule) e.g. alpha-galactoceramide
71
What is DC vaccination?
a-galactoceramide molecules are loaded onto DCs and this boosts the NK T cell population It is used to kill tumour cells
72
Describe CD1
Encoded outside MHC Specialised binding groove presents glycolipids or phospholipids Many lipids and glycolipids differ between microbes and mammals Recognised by specialised subsets of TCR - Va24/Vb11
73
What are gamma delta T cells?
Unconventional T cells Mechanism of selection largely unknown Generally enriched in mucosal and epithelial tissues MHC independent Activated by TCR and NK-receptor (NKG2D)
74
What are the functions of gd T cells?
Lysis of infected or stressed cells Cytokine and chemokine production B cell help and IgE production Priming of ab T cells via antigen presentation DC maturation Regulation of stromal cell function via growth factor production
75
How was the gd TCR discovered?
Delta gene found by chance located within the alpha locus Then gamma gene was discovered when trying to look for corresponding chain
76
Describe the loci of the gamma and delta genes
Limited V segments at both loci Delta has numerous D gene segments
77
How does the gd TCR get its diversity?
Junctional diversity leads to potentially many CDR3 sequences
78
What percentage of T cells are gd?
Between 1-10% of peripheral blood T cells
79
What is the TCR responsible for according to animal models?
Localisation of the cell to tissues Murine models - Vg3 localise to intestinal epidermis, Vg5 localise to epithelium Humans - Vg9Vd2 in peripheral blood, Vd1 in epithelial tissue and resident in liver May involve butyrophilin-like molecules (Btnl)
80
What molecule is expressed in intestinal epithelial cells of mice?
Btnl1 or Btnl6
81
What do Btnl1/Btnl6 do?
Activate and home intraepithelial cells for Vg7 T cells to intestinal epithelial cells
82
What molecule is expressed in thymocytes of mice?
Skint1
83
What does Skint1 do?
Induces maturation of Vg5 T cells in the mouse thymus
84
What doe intraepithelial cells for Vg4 in humans bind to?
BTNL3/BTNL8 expressed in intestinal epithelial cells
85
How do Vg9Vd2 T cells become activated in humans?
Bind butyrophilin itself which presents phosphoantigens Particular motif binds the phosphoantigens, changing the external conformation The Vg9Vd2 T cell can then recognise this conformation and become activated
86
What percentage of gd T cells are Vd1?
10-30% of gd T cells in the blood
87
Describe Vd1 T cells
More highly represented in tissue Use TCR and NK receptors to identify tumour targets Recognise CD1d/lipid complexes and NKG2D ligands MHC recognition (allogeneic) Role in homeostasis and stress surveillance
88
What percentage of normal PBLs are Vd2?
4% but can expand rapidly to 60%+ in infections
89
What do Vd2 T cells recognise?
Small phosphoantigens e.g. isopentenyl pyrophosphate (IPP) and E-4-hydroxy-3-methyl-but-2-enyl-pyrophosphate (HMBPP) presented by butyrophilin3A1 Can also recognise NKG2D ligands
90
Describe butyrophilin
Part of the B7 receptor family-like proteins 2 extracellular Ig-like domains Does not appear to present pAg on the usual, MHC-like way
91
What are the types of butyrophilin?
BTN3A1, A2 and A3
92
What is BTN3A1 essential for?
pAg recognition
93
What region of BTN3A1 binds pAg?
Intracellular region 30.2
94
What does binding of pAg to BTN3A1 do?
Changes the conformation of the extracellular portion of BTN3A1 Allows it to be recognised by Vg9Vd2 cells
95
What are effector functions of gd T cells?
Cytokine production - Th1-like prod IFN-g and TNF-a, Th17-like prod IL-17 Cytotoxicity against infected or transformed cells Degranulate like NK cells, perforin, serine esterases, granulysin Thought to be a rapid response in immunosurveillance
96
What drugs are used in gd T cell therapy?
Aminobisphosphonates Pamidronate Alendronate Zoledronic acid
97
What does gd T cell therapy do?
Blocks mevalonate pathway and causes accumulation of IPP IPP binds 30.2 region of BTN3A1 and causes activation of Vg9Vd2 T cells
98
What is BCG?
Bacille Calmetter-Guerin A vaccine form of Mycobacterium bovis used to prevent tuberculosis and other mycobacterial infections
99
What is the significance of BCG in relation to gd T cells?
BCG activates Vg9Vd2 cells and these cells are better at killing tumours than zoledronic acid

Infection and Immunity (33 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2025 Bold Learning Solutions. Terms and Conditions