Advanced immunology Flashcards

Lectures: -Week 3, day 4, lecture 1: Advanced lectures - Innate lymphocytes -Week 3, day 4, lecture 2: Advanced lectures - NK-cells -Week 3, day 4, lecture 3: Advanced lectures - Regulatory T-cells (76 cards)

1
Q

Which 3 important B- and T-cell interactions take place in the lymph node?

A
  1. TCR <-> MHCII
  2. C40 <-> CD40L
  3. Cytokines
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What additional signal do T-cells give to B-cells which have been activated through their BCR?

A

CD40/CD40L

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

Which mechanisms allow B-cells to be activated independent of T-cells?

A
  1. Crosslinking of BCR’s by repetitive antigens
  2. TLR’s
  3. BAFF
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What is the difference between a T-cell dependent and T-cell independent response?

A
  1. A T-cell dependent B-cell response leads to
    -Extrafollicular response: the formation of plasma cells that produce IgM
    -B-cells that undero the germinal centre reaction, resulting in B-cells with a higher affinity:
    –Non-IgM plasma cells (class switch)
    –Memory B-cells
  2. A T-cell independent B-cell response solely leads to the formation of IgM-producing plasma cells, without affinity maturation, class switch recombination or formation of memory B-cells
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What is the approximate response time of an adaptive B-cell response?

A

~10 days

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

Which types of innate-like lymphocytes can be identified? (4)

A
  1. NK T-cells
  2. B1-cells
  3. γδ-T cells
  4. Marginal zone B-cells
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Where do innate-like lymphocytes typically occur?

A

Anatomical locations contacting the outside world, such as mucosal surfaces and the pleural & peritoneal cavity

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

What is special about the TCR/BCR repertoire of innate-like lymphocytes?

A

They have a very limited receptor repertoire

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

Do innate-like lymphocytes have TCR/BCR’s?

A

Yes, but with a limited diversity

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

Why can innate-like B-cells always respond independent of T-cells?

A

They are present in a pre-activated state, only requiring BCR activation to become active

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

Which types of innate lymphoid cells can be identified? (4)

A
  1. ILC1
  2. ILC2
  3. ILC3
  4. NK-cells
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Where do innate lymphoid cells typically occur?

A

Anatomical locations contacting the outside world, such as mucosal surfaces and the skin

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

Do innate lymphoid cells have a TCR/BCR?

A

No, they don’t

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

How are innate lymphoid cells activated?

A

By cytokines in their surrounding

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

Which two types of innate-like B-cells can be identified?

A
  1. Marginal zone B-cells
  2. B1-cells
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Where do B1-cells occur?

A

In the peritoneum and pleural cavity

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

Where do marginal zone B-cells reside? Why is this location advantageous?

A

In the marginal zone of follicles in the white pulp in the spleen; this location is advantageous because they directly contact blood flowing along the follicles in sinuses, allowing them to rapidly respond to sepsis

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

How are marginal zone B-cells activated?

A

Marginal B-cells are already pre-activated and require relatively little stimulation; this stimulation is provided by repetitive patterns on bacterial antigens encountered during sepsis

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

Which type of antibody is produced by marginal zone B-cells, and why?

A

IgM, because these cells never undergo a germinal centre reaction and thus never undergo class switch recombination

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

What are natural antibodies?

A

Natural antibodies are a ‘first line of defence’, produced by B1-cells without prior experience to antigens

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

What is an important example of natural antibodies, and why?

A

Blood group antibodies, because they prevent blood transfusion to persons with a different blood group

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

What kind of groups are natural antibodies targeted at? Why is this advantageous?

A

Non-protein antigens such as glycolipids & carbohydrates; these are often found on bacteria

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

How are B1-cells selected? How does this help them in their function?

A

They are selected on the basis of low-level autoreactivity; this is not harmful to the body, but does cause them to continuously produce antibodies

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

True or false: in a healthy individual, antibodies produced by ‘regular B-cells’ (non-B1) are in the majority

A

False; in a healthy individual, the continuous production of antibodies by B1-cells is responsible for the majority of the antibodies in the serum

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
True or false: the natural antibody titre increases during an infection
False; the titre of natural antibodies is more ore less constant
26
How is the limited BCR repertoire of MZ-B-cells and B1-cells achieved?
Some V(heavy chain)'s are restricted to specific V(light chains) -> semi-invariant receptors
27
What is an important compound, commonly found throughout the body, that is responsible for positive selection of MZ-B-cells & B1-cells?
Phosphatidylcholine (PtC)
28
What happens to MZ-B-cells/B1-cells that don't recognize PtC?
They lack the signal needed for positive selection and undergo apoptosis
29
What kind of antigen do NK T-cells recognize? Which receptor do they use?
Glycolipids, recognized through CD1
30
How are NK T-cells activated?
Through the TCR
31
What is the primary location of NK T-cells?
Peripheral tissues
32
What are the main functions of NK T-cells? (2)
1. Cytokine production 2. Defence against mycobacteria
33
True or false: NK T-cells have a limited receptor repertoire
True; they have an invariant alpha-chain and a limited subset of beta-chains
34
Where are γδ-T cells produced?
The embryonic thymus
35
What is the primary location of γδ-T cells?
Epithelial tissues
36
What are the main functions of γδ-T cells? (2)
1. Cytotoxicity 2. Immune regulation
37
On the basis of which markers can innate lymphoid cells be identified?
Lineage(neg), CD45(pos)
38
True or false: innate lymphoid cells have a TCR/BCR
False; they don't have such a receptor
39
How are ILC's activated?
Through cytokines, specifically IL-7
40
What do ILC's do when activated?
Produce a large amount of cytokines upon activation
41
To which type of cells are ILC1's analogous?
Th1-cells -> cause macrophage activation and oxygen radicals through secretion of IFN-γ
42
Which transcription factor can be found in both ILC1's and Th1-cells?
T-bet
43
To which type of cells are ILC2's analogous?
Th2-cells -> secrete IL-4, IL-5 & IL-13, important for extracellular matrix/tissue repair, but also in allergy
44
Which transcription factor can be found in both ILC2's and Th2-cells?
Gata3
45
To which type of cells are ILC3's analogous?
Th17-cells -> produce IL-17, IL-22, important for phagocytosis & epithelium survival
46
Which transcription factor can be found both in ILC3's and Th17-cells?
RORγt
47
How are ILC2's activated?
Alarmins, which get released when epithelium gets damaged
48
In which way are ILC2's an example of neuro-immuno interaction?
They are controlled by neurotransmitters
49
What are the two general functions of ILC's?
1. Tissue homeostasis 2. Rapid responses through the production of cytokines
50
What is the main activator of NK-cells?
IFN
51
What are the three main functions of NK-cells?
1. Rapid killing of virus-infected, stressed & malignant cells 2. Rapid pro-inflammatory cytokine production 3. Regulators of immune responses
52
What is the process of release of granzyme/perforin granules? (3)
1. Granules containing granzyme/perforin are present in the cytoplasm 2. Granules get moved to the site of the target cell by microtubule transport 3. Exocytosis of granules
53
What is the function of perforin and what is the function of granzyme in perforin/granzyme cytotoxicity?
Perforin produces pores in the membrane of target cells, allowing granzyme to enter and activate apoptosis pathways
54
True or false: all cells of the immune system use the same granzyme
False; there are multiple kinds of granzyme NK-cells make use of the highest amount of different granzymes
55
In addition to killing by cytokines, which other ways do NK-cells have for cytotoxic effects?
Receptor-ligand interactions, such as: 1. FAS/FASL 2. TRAIL/TRAILR
56
What is ADCC?
Antibody-dependent cell-mediated cytotoxicity
57
How do NK-cells recognize cells that are marked for cytotoxicity by antibodies? How do they differentiate between cells with low and cells with high levels of antibody?
They recognize the FC-tails of IgG using FC-γRIII (CD16); CD16 has a higher affinity for multimeric IgG, which occurs in antigen-antibody complexes or when IgG is bound to a cell
58
Which cytokines are produced in high levels by NK-cells? (2)
1. IFN-γ 2. TNF-α
59
How do NK-cells interact with macrophages?
At the start of infection, NK-cells are activated by cytokines produced by macrophages (IL-12, IL-18) They then produce cytokines that activate more macrophages (GM-CSF, TNF-α)
60
Which four reasons cause NK-cells to be classed as innate immune cells?
1. Rapid responses without clonal expansion/differentiation into effector cells 2. No antigen-specific receptor that requires gene rearrangement 3. Ready-to-use germline-encoded inhibitory & activating receptors that are reduced on stresses/infected/malignant cells 4. No formation of memory cells with higher affinity after activation
61
What are the common markers for NK-cells?
CD3- & CD56+
62
Which two subsets of NK-cells can be identified?
1. CD56(bright) 2. CD56(dim)
63
Which are in the majority in the blood: CD56(bright) or CD56(dim) NK-cells?
CD56(dim) NK-cells form ~90% of NK-cells found in the blood
64
Which are in the majority in the lymph nodes: CD56(bright) or CD56(dim) NK-cells?
CD56(bright) NK-cells form ~75% of NK-cells in the lymph nodes
65
Which NK-cells are the Iargest NK-population in the body: CD56(bright) or CD56(dim) NK-cells?
CD56(dim) form 90% of the total NK-cells in the body
66
What are the characteristics of CD56(bright) vs CD56(dim) NK-cells? (4)
1. Cytotoxicity is higher in CD56(dim) than in CD56(bright) NK-cells 2. ADCC is higher in CD56(dim) than in CD56(bright) NK-cells 3. CD56(dim) cells have a slower cytokine production than CD56(bright) cells 4. CD56(bright) cells modulate APC's using cytokines, whereas CD56(dim) cells are responsible for tissue surveillance for virus-infectes/stressed/malignant cells
67
How do NK-cells recognize which cells are healthy and which cells are diseased?
NK-cells are switched off when they encounter a healthy cell, because these cells express inhibitory singals
68
What is a cue that causes NK-cells to identify 'missing self'? Why is this advantageous?
NK-cells are activated when the encounter cells with low/no MHCI-expression This is advantageous because both viruses and tumours often downregulate MHCI to prevent CD8+ T-cell responses -> NK-cells are still able to identify and kill these cells
69
What are KIR-molecules?
Killer immunoglobulin-like receptors; inhibitory & activating receptors found on NK-cells
70
What do KIR-molecules recognize?
Specific motifs on MHC-molecules
71
Why is there a large array of KIR-molecules?
Because they recognize specific motifs on MHC-molecules, and because MHC-molecules are highly diverse (within the population), there also needs to be a wide variety of KIR-molecules
72
KIR-L's are often [inhibitory/activating]. How can this be identified intracellularly?
Inhibitory; have a large intracellular domain
73
KIR-S's are often [inhibitory/activating]. How can this be identified intracellularly?
Activating; have a small intracellular domain
74
How can NK-cells dampen immune responses?
Lysis of activated T-cells to downregulate the immune response
75
How can NK-cells have immune memory? How do they respond differently from 'normal' NK-cells? (4)
Recurrent infection leads to expansion of virus-specific NK-cells Response: 1. Stronger ADCC 2. Higher cytokine release 3. Lower response to IL-12/IL-18 4. Possibly lower T-cell regulation
76