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x- Immunology MICR 3230 > B cell Activation/ Differentiation/ Memory Generation > Flashcards

B cell Activation/ Differentiation/ Memory Generation Flashcards

1
Q

How many types of antigen receptors does each B cell have?

A

1 single type- many copies

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2
Q

What describes how upon stimulation, each B cell creates clones of cells with same antigen receptor?

A

Clonal selection hypothesis

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3
Q

When do B cells make clones?

A

once activated/ selected for

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4
Q

Where does stem cell maturation into immature committed B cells occur?

A

Bone marrow

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5
Q

Where does antigen-dependant proliferation/ differentiation into plasma/ memory cells occur?

A

Peripheral lymphoid tissue

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6
Q

What are B cells that have the BCR but have not encountered antigen called?

A

Immature B cells

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7
Q

What can mature B cells differentiate into?

A

memory cells
plasma cells (produce antibodies)

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8
Q

What are the two B-cell responses?

A

T-dependant = TD
T-independent = TI

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9
Q

What B cell response requires help from T cells?

A

T-dependent

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10
Q

What B cell response does not require T cell help?

A

T-indipendent

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11
Q

What B cell response is typically initiated upon antigen recognition?

A

T-dependent

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12
Q

What B cell response is generated upon exposure to multivalent/ polymerized antigen? (more complex)

A

T-indipendent

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13
Q

How does a TI-1 antigen bind to B cells?

A

through PRRs/ mlgs (Ig)

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14
Q

How does a TI-2 antigen bind to B cells?

A

cross-link large # of BCRs

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15
Q

How many T-independent (TI) forms are there?

A

2 = TI-1/ TI-2

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16
Q

What is the 3-front attack of the T-dependent B-cell response?

A
  1. Directly bind antigen
  2. T helper cell binds to/ interacts with B cell
  3. TH cell activated- release cytokines/ activate B cell
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17
Q

How do B cells bind antigens?

A

BCR
- initial activation/ proliferation

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18
Q

How is some antigen presented on B-cell surface?

A

some antigen internalized/ processed
- presented on cell surface MHC class II molecules

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19
Q

What does TI-1 antigen bind to?

A

B cells

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20
Q

What does TI-2 antigen bind to?

A

Cd3 complement components
cross-link receptors

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21
Q

What receptors is the TI-1 antigen associated with?

A

Ig and innate
- signalling from both

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22
Q

What is CD21?

A

complement receptor

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23
Q

What does a T-dependent antigen require to generate an antibody response?

A

T-cell help

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24
Q

What happens in a T-dependent cell response if you only have B or T cells alone? (mice experiment)

A

no activation point

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25
Q

What are the 3 steps in T-dependent B-cell response?

A
  1. BCR signalling
  2. Co-stimulatory interaction/ present antigen to TH cell
  3. Cytokine signalling- activate B cell
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26
Q

What can individual activated B-cells differentiate into?

A
  • entry to germinal centre
  • IgM memory cell
  • plasma cells (secrete antibodies)
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27
Q

What part of the lymph node is the B-cell zone?

A

Follicle

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28
Q

What part of the lymph node is the T-cell zone?

A

Paracortex

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29
Q

For the T-dependent B-cell response why is the antigen endocytosed once bound to BCR?

A

present to T cells

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30
Q

What are the 2 ways for an antigen to be endocytosed into B cell?

A

Lysosomal proteases
Actomyosin fibers

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31
Q

What cleaves antigen off surface of APC for endocytosis into B cell?

A

Lysosomal proteases

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32
Q

What exerts a pulling force on BCR with a high affinity to bring whole antigen/ APC into B cell? (whole BCR)

A

Actomyosin fibers

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33
Q

What are the 5 steps for BCR antigen endocytosis?

A
  1. Polymerization/ close contact
  2. Pull clusters to centre of contact (inc affinity)
  3. Initiate uptake
  4. Enodyctosis with APC fragments
  5. Endocytosis complete
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34
Q

What induces internalization (endocytosis of antigen by B cell) and antigen presentation?

A

Antigen receptor clustering

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35
Q

When are BCR-antigen complexes internalized?

A

endocytosis once signaling begins

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36
Q

How are endocytosed antigen fragments presented on B-cell surface to solicit T-cell help?

A

MHC class II molecules on B cell surface

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37
Q

What co-receptors are upregulated by antigen engagement? (B-T cell interaction)

A

CD40/ CD80/ CD86

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38
Q

When are germinal centres formed?

A

after/ once B cells activated

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39
Q

Where are germinal centres in lymph nodes?

A

inside follicle (B-cell zone)

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40
Q

Where in the lymph node is the [ ] of activated B-cells?

A

germinal centre

41
Q

What are antibody/ Ig-secreting cells?

A

plasma cells

42
Q

What is the plasma cell fate of a B-cell?

A

antibody secretion

43
Q

What is the germinal centre fate of a B-cell?

A

SHM antigen-mediated selection

44
Q

What dictate the fate of antigen-activated B cells?

A

transcription factors in regulatory network

45
Q

What transcription factor promote germinal centre B cells?

A

Pax5/ Bcl-6

46
Q

When do Pax-5/ Bcl-6 promote germinal centre B cells?

A

when coupled with low IRF-4 levels

47
Q

What transcription factor promotes B-cell plasma cell?

A

BLIMP-1

48
Q

When does BLIMP-1 promote B-cell plasma cells?

A

when coupled with high IRF-4 levels

49
Q

When during the immune response are plasma cells/ Ig-secreting cells found in lymph node?

A

first 5-6 days

50
Q

What type of B-cell bears cell surface IgM but does not secrete antibodies?

A

Naive B-cell

51
Q

What happens when a naive B-cell interacts with an antigen?

A

becomes plasmablast

52
Q

What are AFCs?

A

antibody-forming cells
= plasmablasts/ plasma cells

53
Q

What are differentiated B-cells that have begun to secrete antibodies but not yet lost capacity to proliferate?
- still bear cell surface BCRs

A

Plasmablasts

54
Q

What prevents free diffusion of lymph fluid into the lymph nodes? (lines the subscapular sinus region)

A

SCS
- control lymph node structure

55
Q

What is the relative lag period of Naive vs Memory B-cells?

A

Naive- longer
Memory- shorter

56
Q

What is the relative time of peak response of Naive vs Memory B-cells?

A

Naive- longer
Memory- shorter

57
Q

What is the relative magnitude of peak antibody response of Naive vs Memory B-cells?

A

Naive- varies
Memory- strong/ specific

58
Q

What antibody isotype is produced by Naive B-cells?

A

IgM

59
Q

What antibody isotype is produced by Memory B-cells?

A

IgG/ IgA = class switching

60
Q

What is the relative antibody affinity of Naive vs Memory B-cells?

A

Naive- low
Memory- high

61
Q

What is the relative life span or Naive vs Memory B-cells?

A

Naive- short
Memory- long lived

62
Q

Can naive B-cells recirculate?

A

yes

63
Q

Can memory B-cells recirculate?

A

yes

64
Q

What is SHS?

A

Somatic hypermutation
- affinity selection

65
Q

Where does somatic hypermutation occur?

A

within germinal centre

66
Q

What produces individual point mutations in Ig-heavy and light chain rearrangements? (variability)

A

SMS

67
Q

What increases the affinity of an antibody for an antigen over time?

A

AID = activation-induced cytidine deaminase

68
Q

How do SHS point mutations increase?

A

overtime/ with repeated exposures

69
Q

What followed by affinity selection results in increased affinity for antigen over time?

A

Mutations (SHM)

70
Q

What is enzyme AID induced by?

A

Bcl-6

71
Q

What enzyme is responsible for both SHM and CSR?

A

AID = activation-induced cytidine deaminase

72
Q

What is CSR?

A

class switching recombination

73
Q

What turns down the expression of DNA damage response genes that might interfere with genetic changes generated during SHM?

A

AID

74
Q

What happens to B-cells in the germinal centre?

A

optimation (optimize for future efficient response)

75
Q

What happens to a B-cell when it enters the germinal centre?

A

proliferation and SHM (somatic hypermutation)

76
Q

What is the traditional antibody isotype produced by naive B-cells?

A

IgM/ IgD

77
Q

What is the process of expressing any heavy chain class other than IgM/ IgD? (naive ones)

A

Class switch recombination

78
Q

Where does class switch recombination occur?

A

germinal centre
- after antigen contact

79
Q

What regions does recombination occur between?

A

donor/ acceptor switch (S) regions

80
Q

What are the donor/ acceptor switch (S) regions?

A

tandem repeats of short G-rich sequences
= 20-80 bp long
- contain targeting sites for AID

81
Q

What contains target sequences for AID (enzyme)?

A

Switch (S) regions
- repeats short G-rich sequences

82
Q

What must B cells receive to engage in CSR (class switch recombination)?

A

costimulatory signals from CD40

83
Q

What determines what isotype is produced in CSR?

A

which cytokine signal is received

84
Q

What are the different isotypes that can arise in CSR (from IgM/ IgD)?

A

IgG/ IgE/ IgA

85
Q

What stimulates the transcription of sterile RNAs from germ-line promoters?

A

Cytokines

86
Q

What is critical to CSR activity?

A

sterile RNA

87
Q

What would happen if no CD40L in T cells?
- costimulatory molecule

A

not activated- no cytokines produced/ no CSR activity

88
Q

What cytokine signal can produce class switching to IgG or IgE?

A

IL-4

89
Q

What cytokine signal can produce class switching to IgA or IgG?

A

TGF

90
Q

What cytokine signal can produce class switching to IgA?

A

IL-5

91
Q

What cytokine signal can produce class switching to IgG?

A

IFN-y

92
Q

What T-independent B-cell response is associated with bacterial cell wall components?

A

TI-1

93
Q

What T-independent B-cell response is associated with capsular polysaccharides?

A

TI-2

94
Q

What are the 2 subclasses of B-cells that regulate the T-independent antigen response?

A

B-1 B cells
Marginal zone B cells

95
Q

Do T-Independent B cells also go to germinal centre?

A

no- not same response as T-dependent

96
Q

What B-cell subclass for TI response produces IgM
“natural antibodies” that bind broad antigens with low affinity?

A

BI-1 B cells

97
Q

What B-cell subclass for TI response must receive low-level signals through BCR for survival?

A

Marginal zone B-cells

98
Q

What B-cell subclass TI is specialized to respond to blood-borne antigen entering immune system through spleen?

A

Marginal zone B-cells

99
Q

What B-cell subtype can renew themselves in the periphery?

A

Marginal zone B-cells

x- Immunology MICR 3230 (11 decks)

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