Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

A10HA > 9 - The Lymphoid Cells - Natural Killers and Others > Flashcards

9 - The Lymphoid Cells - Natural Killers and Others Flashcards

1
Q

Cells in bone marrow

A
  • myeloid progenitor
  • common lymphoid progenitor
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Immune cells from myeloid progenitor

A
  • neutrophil (B-helper NT?) >90%
  • basophil
  • eosinophil
  • monocyte -> macrophage (M1, M2, Reg)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Immune cells from common lymphoid progenitor

A
  • Natural killer cell (innate)
  • lymphocytes (adaptative)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Lymphoid cell line

A
  1. Multipotential hematopoeitic stem cell (hemocytoblast)
  2. common lymphoid progenitor
  3. small lymphcyte (cont.) OR natural killer cell (END)
  4. small lymphocyte
  5. B lymphocyte (cont.) OR T lymphocyte (END)
  6. plasma cell
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What happened 2011?

A

Things got more complicated in 2011 due to advances in molecular biology
- further sub-sets of innate lymphoid cells (ILCs) defined on basis of cytokine expression and transcription factor regulation
- no longer differentiated in terms of morphology: defined on cytokine expression and transcription factor regulation

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

Structure of innate lymphoid cells (ILCs)

A
  • common morphology, but vary in expression of cell-surface molecules
  • ILCs express cytokine receptors (e.g., for interleukins), lack antigen specificity, i.e., do not express T or B cell receptor
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Types of ILCs

A
  • there are cytotoxic and non-cytotoxic ILCs
  • cytotoxic include NK cells
  • non-cytotoxic include T-bet cells, GATA3 ILC2s and RORyt ILC3s (transcription factors then ILC-Xs)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Effects of NK cells

A
  • immunity to viruses and cancer
  • chronic inflammation
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Effects of ILC1s

A
  • immunity to intracellular bacteria and protozoa
  • chronic inflammation
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Effects of ILC2s

A
  • immunity to helminths
  • asthma and allergic diseases
  • metabolic homeostasis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Effects of ILC3s

A
  • lymphoid tissue development
  • intestinal homeostasis
  • immunity to extracellular bacteria
  • chronic inflammation
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

How are ILCs differentiated from lymphocytes?

A

They do not express T or B cell regulators

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

Importance of NKC

A

NKC - perforin and granzyme important
- defence against virally infective cells
- separate from ILC1 as ILC1 involves immunity to bacteria and protozoa as opposed to viruses

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

How are ILCs distinguished from NK cells?

A

By transcription factors

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

How many groups of ILCs

A

3

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

ILC group 1

A
  • interferon gamma production
  • UNABLE to produce TH2 and TH17 cell-assoc. cytokines
  • defined by what they can’t produce
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

ILC group 2

A
  • require IL-7 for development
  • defined by what they require
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

ILC group 3

A
  • defined by IL-17 & IL-22 production
  • defined by what they produce
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Characteristics of natural killer cells

A
  • Large, lymphocyte-like cells but possess small granules containing perforin & granzymes
  • Kill other cells (eg cancer or virus-infected cells) usually without antibody
  • Produce cytokines, such as TNFα, interferon & some interleukins
  • Comprise ca. 15 % of all blood leucocytes

-Ca. 7 -12 μm diam.

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

ILC vs NK granules

A

NK have more granules in cytoplasm tan ILC if viewed on a microscope

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

How do they target/kill other cells?

A
  • NK cells target other cells rather than directly targeting microbial life
  • usually kill without antibody but not always
22
Q

Physiological NK cell functions (4)

A
  1. healthy cells - balance of signals delivered by activating and inhibitory receptors regulates he recognition of health cells by NK cells
  2. missing self - tumour cells that down regulate major histocompatabiliy complex (MHC) class I molecules are detected as ‘missing self’ and are lysed by NK cells
  3. induced self-ligands - tumour cells can overexposes induced stress ligands recognised by activation NK cell receptors, which override the inhibitory signals and elicit target cell lysis
  4. ADCC - tumour antigen specific antibodies bind to CD16 and elicit antibody dependent NK cell-mediated cytotoxicity
23
Q

Physiological NK cell functions: healthy cells

A

Healthy cells display stimulatory ligand which attached to the activating receptor
- no lysis as normal
- inhibitory is key to tell the NK cell that is is a normal healthy cell and inhibitory receptor is binding

24
Q

Physiological NK cell functions: inhibitory binding missing/ missing self

A

Could have abnormal MHC (could be transformed), or MHC could be completely deficient which triggers NK cell

25
Q

Physiological NK cell functions: damaged or stress cell/ induced self ligands

A
  • can still have inhibitory signal however there is an excess of activating receptors
  • increase of stimulation and activation of binding
  • stress is sufficient to cause lysis - overriding the inhibitory signal
26
Q

Physiological NK cell functions: antibody dependent cell cytotoxicity/ ADCC

A
  • tumorous cell
  • antibodies generated against normal antigens on tumour cells can trigger activation of NK cell
  • fairly generalised receptor on NK cell which recognises these antibodies
27
Q

What is the action of NK cells mediated by?

A

Action of NK cells is mediated by a balance of inhibitory and activating receptors

28
Q

Inhibitory vs. activating receptors

A

INHIBITORY:
- tolerance to self
- KIR2DL, KIR3DL, LIR/ILT, NKG2A, LAIR
- contain ITIM (immunoreceptor tyrosine-based inhibitory) motif in cytoplasmic tail
- ITIM recruits phosphates, which antagonise activation

ACTIVATING:
- responsiveness to pathogens
- KIR2DS, KIR3DS, LIR/ILT, NKG2C/E, NKG2D, NKR-P1, NKp30, NKp44
- associate with accessory proteins containing ITAM motifs (immunoreceptor tyrosine based activating motif)

29
Q

What does KIR stand for

A

Killer immunoglobulin-like receptors

30
Q

How do natural killer cells differ?

A

Each NK differs in combination of KIR genes expressed. Within an individual organism, all KIR genes are expressed on some NK cells, giving repertoire of responsiveness

31
Q

How does KIR differ in a population

A

Within a population, individuals have different combinations of KIR genes and alleles, therefore NK cell repertoires differ

32
Q

How does KIR differ in humans?

A
  • Within the human species, ethnic populations differ in the presence and frequency of KIR genes
  • Human KIR genes differ markedly from those in other primates
33
Q

Features of KIRs

A

Doesn’t have a signal inhibitor receptor or activating receptor
- diversity of both types
- inhibitory receptors contain a certain motif
Binding of inhibitory receptor and recruitment of phosphates

34
Q

How likely is it that just one NK cell type exists?

A
  • highly unlikely
35
Q

What was found that shows more than one NK cell exists?

A

Found that there are bright cells and dim cells (CD56 marker)
- determined cytotxicity
- bright cells - cytokine producers
- low reactivity
- CD56 dim are cytotoxic

36
Q

What is CD56?

A

Neural cell adhesion molecule (NCAM)
- phenotypic marker for NK cells

37
Q

NK cell differentiation stages

A
  1. Human NK cells arise from the HSC in the bone marrow and then progress to pro-, pre-, and immature NK cells (also referred to as stage 1, 2, and 3 NK cells, respectively).
  2. The immature NK cell transits to the peripheral lymphoid compartment secondary lymphoid tissues where CD56bright NK cells predominate.
  3. CD56bright NK cells are also referred to as stage 4 NK cells, and current evidence suggests that they develop in the secondary lymphoid tissues into CD56dim mature NK cells (stage 5)
38
Q

What does research into bright/dim reactivity show?

A

The present work suggests a role for MCM4 in the transition of CD56bright to CD56dim NK cells, as evidenced by the relative absence of CD56dim NK cells in the peripheral blood with the preservation of the CD56bright NK cell population

39
Q

What is proposed to drive NK function?

A

Proposed hat metabolism, not phenotype, drives function
- spectrum of types
- metabolism of types drives function

40
Q

What determines whether a cell is a cytotoxic, a regulatory, or a memory NK?

A
  • cytotoxic: glucose-fuelled metabolism
  • regulatory: low glucose metabolism
  • memory: mitochondrial fitness (change in membrane potential)
41
Q

ILC functions summary

A
  • NK/ILC1 –> M1 –> immunity to viruses, intracellular bacteria and parasites
  • ILC2 –> M2 –> immunity to helminths
  • ILC3 –> cytokine production –> imunity to extracellular bacteria
42
Q

ILC interactions with other cell types

A

Three main cell types targeted for interaction:
- non-haematoloeitc stromal/epithelial cells
- myeloid cells
- adaptive lymphocytes

43
Q

Types of non-haematopoietic cells, myloid cells, and adaptive lymphocytes

A
  • non-haematopoietic cells: epithelial or stromal cells
  • myeloid cells: DC macrophage, monocyte or granulocyte
  • adaptive lymphocytes: effector T cell, FOXP3+, Treg Cell
44
Q

Interactions between ILC and non-haematopoietic cells

A

ILC —–> non-haematopoietic cells : tissue-trophic factors
non-haematopoietic cells —–> ILC : alarmins, cytokines and ‘stress’ ligands

45
Q

Interactions between ILC and myeloid cells

A

ILC —-> myeloid cells : ‘helper’ cytokines
myeloid cells —-> ILC : innate cytokines

46
Q

Interactions between ILC and adaptive lymphocytes

A

ILC —-> adaptive lymphocytes : ‘helper’ cytokines, antigen presentation
adaptive lymphocytes —-> ILC : regulation

47
Q

Where do blood cells arise from?

A

Blood cells arise from the myeloid or lymphoid progenitors, with the latter giving rise to natural killer (NK) cells (innate) and lymphocytes (adaptive).

48
Q

How have lymphoid cells been classified?

A

Lymphoid cells have been re-classified into at least three different groups of innate lymphoid cells (ILC), which include the NK cell type. NK cells either regarded as separate ILCs or classed as part of ILC1 group.

49
Q

What do NK cell recognise?

A
  • NK cells recognise cells infected by viruses or other intracellular pathogens, as well as transformed or malignant cells.
  • Recognition mediated by binding via MHC Class I, as well as inhibitory and activating killer immunoglobulin-like receptors (KIR)
50
Q

NK phenotypes

A

NK cells have 2 major phenotypes: CD56 bright/dim

51
Q

Grouping of ILCs

A

Main ILC groups defined by their reactivity to certain cytokines, different transcription factors and cell:cell interactions

A10HA (18 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions