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Immunology and Virology > Week 13 > Flashcards

Week 13 Flashcards

1
Q

What are the 5 classes of Ig?

A 
IgM
IgD
IgE
IgA
IgG
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2
Q

Abs are the secreted form of what?

A

the BCR

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3
Q

What is the Ab repertoire?

A

The total number of Ab specificities available to an individual - is at least 10^11 in humans

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4
Q

What are hyper-variable regions?

A

Designated/concentrated regions of sequence variability in the variable regions of both the heavy and light chain

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5
Q

What are complementarity determining regions (CDRs)?

A

Same as hyper variable regions (concentrated areas of sequence variability on VH and VL)

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6
Q

How many hyper variable regions are there within the heavy and light chain?

A

6 (2 sets of HV1, HV2, HV3 combination)

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7
Q

What determines the antigen specificity of an Ab?

A

The combination of the 6 HV regions on the VH/VL chains (combinatorial diversity)

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8
Q

What are the 3 key things that create diversity in the Ig repertoire?

A

Combinatorial diversity
Junctional diversity
Somatic hyper-mutation

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9
Q

How does combinatorial diversity create Ig repertoire diversity?

A

Mx copies of each gene segment type, different combinations of gene segments
Different combinations of H and L V regions

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10
Q

How does junctional diversity create Ig repertoire diversity?

A

Can have addition/subtraction of nucleotides at joints b/w different gene segments

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11
Q

How does somatic hypermutation create Ig diversity?

A

After an immune response is initiated, point mutations are introduced into the rearranged V region genes

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12
Q

How does B-cell DNA differ to gremlin DNA?

A

V and C regions have been brought closer in B cell DNA

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13
Q

What are the 3 DNA segments that encode VH?

A

V D and J

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14
Q

What are the DNA segments that encode VL?

A

V and J

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15
Q

What are the 3 DNA segments that encode alpha chains of the TCR?

A

V D and J

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16
Q

What are the DNA segments that encode beta chains of the TCR?

A

V and J

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17
Q

What are RAG1 and RAG2?

A

Genes encoding for proteins that are part of the V(D)J recombinase protein complex

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18
Q

How are RAG1 and RAG2 involved in gene rearrangement?

A

Encode lymphoid specific parts of the V(D)J recombinase protein complex, which helps effect somatic recombination

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19
Q

What happens in the early pro-B cell stage of B development?

A

Heavy chain locus rearranged - D segment joined to J segment

RAG1 and RAG2 genes induced

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20
Q

What happens in the late pro-B cell stage of B development?

A

Rearrangement so V segment added to the DJ sequence - if successful μ heavy chains produced in cytoplasm
Pre-BCR produced –> signals transition to pre-B cells

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21
Q

Out of the heavy and light chains, which is rearranged first in B cell development?

A

Heavy chain is rearranged first (D to J joining = first step)

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22
Q

What happens in the pre-B cell stage of B development?

A

Pre-BCR signalling enforces allelic exclusion
Further rearrangement of H chain locus halted, begin L chain locus rearrangement
Many able to generate progeny w/ IgM molecules (=immature B cells)
L chains display isotypic exclusion (express only one type of light chain)

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23
Q

What is allelic exclusion?

A

Only one of the two alleles of a gene is expressed in a diploid cell

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24
Q

At the pre-B cell stage of B cell development, L chains display isotypic exclusion - what does this mean?

A

They only express one type of light chain (κ or λ)

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25
Q

Roughly what is the ratio of κ to λ light chain expressing B cells in humans?

A

65% : 35%

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26
Q

The BCR is composed of two key parts - what are they?

A

Membrane-bound Ig molecule of one isotype (D, M, A etc)

Ig⍺/Igβ heterodimer (CD79)

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27
Q

What is central tolerance?

A

The process of eliminating any developing T or B cell that is autoreactive

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28
Q

What are the general stages of B cell development?

A 
Early pro-B cell
Late pro-B cell
Pre-B cell
Immature B cell
Mature B cell
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29
Q

What happens in the immature B cell stage of B cell development?

A

Rearranged light chain paired w/ μ chain
IgM can be expressed on cell surface - associates w/ Ig⍺/Igβ to form a functional BCR
Central tolerance - tested for auto reactivity in bone marrow
Peripheral tolerance - does same in periphery, secondary check in case any escape central
If successful can continue to mature and are carried to spleen

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30
Q

What is CD79 also known as?

A

Ig⍺/Igβ

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31
Q

What is the Ig⍺/Igβ heterodimer also known as?

A

CD79

32
Q

What does the Ig⍺/Igβ heterodimer do?

A

Associates with IgM to form a functional BCR

33
Q

Where do B cells complete their maturation?

A

B cell follicles in the spleen

34
Q

What happens if cells are self-reacting in development?

A

Receptor editing - autoreactive receptor replaced

Clonal deletion

35
Q

What happens in the mature B cell stage of B cell development?

A

Complete their maturation in B cell follicles in the spleen
Follicles release signals for survival - weak, constitutive signals through BCR and BAFF (cytokine) produced through follicular DCs

36
Q

What is BAFF?

A

A cytokine released by follicular DCs to mature B cells for cell survival

37
Q

Over-expression of BAFF has been linked to what?

A

Development of autoimmune disease

38
Q

What do naive B cells need for activation?

A

Accessory signals from Tfh cells (or microbial constituents)

39
Q

What signals do Tfh cells provide to B cells for activation?

A

CD40L + various cytokines eg. IL-21, IL-6, TGF-β, IL-4 and IFN-γ

40
Q

What is linked recognition?

A

T cells are activated by the same Ag recognised by the B cell (peptide recognised by T cell must physically associated with the Ag recognised by the BCR)

41
Q

What are germinal centres?

A

Areas of lymphoid follicles where there is intense proliferation of B cells

42
Q

What are the 3 key constituents of GCs?

A

A mantle zone contacting resting Bc ells

Two areas of activated B cells - light and dark zone

43
Q

What are GCs composed of?

A

Mainly rapidly proliferating B cells + ≈10% Ag-specific T cells helping

44
Q

Where do centroblasts proliferate?

A

In the dark zone of the GC

45
Q

When centroblasts reduce proliferation and move over to the light zone, what do they become?

A

Centrocytes

46
Q

What do centrocytes do?

A

Increase Ig production

47
Q

What happens in the dark zone of the GC?

A

Centroblasts rapidly proliferate

48
Q

What happens in the light zone of the GC?

A

Centrocytes increase Ig production

49
Q

What are the 3 key processes GC B cells undergo that produce Ab and are more effective in eliminating infections?

A

Somatic hypermutations
Affinity maturation
Class switching

50
Q

Where are centroblasts found?

A

In the dark zone of the GC

51
Q

Where are centrocytes found?

A

In the light zone of the GC

52
Q

What’s found in the mantle zone of the GC?

A

Resting B cells

53
Q

Where are resting B cells found in the GC?

A

Mantle zone

54
Q

How do somatic hypermutations make GC B cells more effective?

A

Introduces random mutations in the V genes which are initiated by activation-induced cytidine deaminase (AID)
The B cell clones produced have subtle differences in specificity and Ag affinity
Mostly have negative effect on BCR ability to bind to original Ag and so are eliminated by apoptosis - prevents rapidly dividing B cells from dividing to excessive no.s

55
Q

What is the name of the enzyme which initiate somatic hypermutations in B cells?

A

Activation-induced cytidine deaminase (AID)

56
Q

What is affinity maturation in the context of B cells?

A

Selection of B cells with improved affinity for Ag - centrocytes whose BCR binds Ag better will present more peptides one their MHC II surface and so receive stronger survival signals from Tfh
Those w/ weaker binding receive weaker survival signals and => apoptotic

57
Q

What are the first Ag receptors expressed by B cells?

A

IgM and IgD

58
Q

What is the first Ab produced in an immune response?

A

IgM

59
Q

When does switching from IgM to other Ig classes occur?

A

After B cells have been stimulated by Ag

60
Q

How is Tfh involved in class switching?

A

Produces cytokines which regulate the selection of the particular C region

61
Q

IL-4 promotes switching to which isotype antibody?

A

IgE

62
Q

IL-4 signalling in class switching activates which TF?

A

STAT6

63
Q

How does IL-4 lead to IgE isotype antibody being made?

A

IL-4 activates STAT6
STAT6 promotes transcription upstream of the Sε region
This creates IgE isotype Ab

64
Q

What does IL-21 promote switching to?

A

IgG1 and IgG3

65
Q

What does TGF-β promote switching to?

A

IgG2b and IgA

66
Q

What does IL-5 promote switching to?

A

IgA

67
Q

In humans, what is the marker of memory B cells?

A

CD27

68
Q

What is a primary antibody response characterised by? (in terms of Ig)

A

Rapid production of IgM, slightly delayed production of IgG

69
Q

What is a secondary antibody response characterised by? (in terms of Ig)

A

Production of small amounts of IgM and much larger amounts of IgG, with some IgA and IgE

70
Q

Which of the Ig classes is the most abundant in healthy adult humans and mice?

A

IgG

71
Q

What is the main function of IgA?

A

Defence at mucosal sites

72
Q

What is the main function of IgG?

A

Most abundant in serum and strongly induced during an immune response

73
Q

What is the main function of IgD?

A

Function not well known; may serve as auxiliary BCR

74
Q

What is the main function of IgE?

A

Defence against parasites but also involved in allergic diseases

75
Q

What is the main function of IgM?

A

First one produced after B cell activation

76
Q

Give 4 key features of the immunopathogenesis of SLE

A

Aberrant immune regulation
Immune complexes are trapped inside tissue and fix complement, causing inflammation
B cells produce autoantibodies (typically have high ANAs)
T cells produce pro-inflammatory cytokines
IL-2 production is low meaning Treg cells are reduced
Immune complexes may trigger IFN production which favours class switching and Ab production

Immunology and Virology (6 decks)

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