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π“˜π“‚π“‚π“Šπ“ƒπ‘œπ“π‘œπ‘”π“Ž > B Cell Activation, Affinity, Maturation & Class Switching > Flashcards

B Cell Activation, Affinity, Maturation & Class Switching Flashcards

1
Q

When does a B cell become a mature B cell?

A

➝ When it is capable of making IgM and IgD

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2
Q

Once a mature circulating B cell encounters a pathogen what does it do?

A

➝ Migrated to the germinal center in the lymph node

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3
Q

Where does the mature B cell undergo affinity maturation and class switching?

A

➝ In the germinal center

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4
Q

What is the function of affinity maturation and class switching?

A

➝ Codes the heavy chain constant region of the B cell

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5
Q

What does affinity maturation do?

A

➝ further hones the variable fragment of the antibody to that particular pathogen

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6
Q

During affinity maturation what signals does the B cell receive and why?

A

➝ Receives signals from T cells about which pathogen the body is dealing with
➝ this is so it switches its heavy chain constant region to deal with the pathogen

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7
Q

What are the two things a B cell can differentiate into?

A

➝ Plasma cells

➝ Memory B cells

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8
Q

What is an antibody made up of?

A

➝ Two heavy chains and two light chains

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9
Q

What part of the antibody makes up the antigen binding variable fragment?

A

➝ The first domains of the light and heavy chain

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10
Q

What is the constant region of the antibody for?

A

➝ Biological effector functions

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11
Q

What is neutralisation and what does it do?

A

➝ Antibodies binding to the docking site of the virus
➝ It prevents the virus from entering the cells
➝ binds to the active site of toxins and neutralises the toxins

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12
Q

What is opsonisation used against and why?

A

➝ mostly bacteria because they are larger than viruses

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13
Q

How is opsonisation done?

A

➝ The antibody tags the surface of bacteria to recruit other cells such as macrophages

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14
Q

What happens once antibodies have opsonised a bacterium?

A

➝ The macrophage has Fc receptors on it’s membrane that bind to the CH2 region of the antibody
➝ The macrophage performs ADCP (antibody dependent cellular phagocytosis) for bacteria

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15
Q

How does opsonisation for tumor cells occur and what happens as a result of this?

A

➝ The antibody tags the tumor cell and recruits NK cells to perform ADCC (antibody dependent cellular cytotoxicity)
➝ NK cells produce chemicals to cause the tumor to apoptose because they are too large to be engulfed

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16
Q

What are the 4 functions of antibodies?

A

➝ Neutralisation
➝ Opsonisation
➝ Opsonisation for tumor cells
➝ Complement fixing

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17
Q

What are the two immune complexes formed by antibodies?

A

➝ A lot antibodies can bind to the surface of the bacteria and cause agglutination which gets cleared by macrophages
➝ complement molecules such as C1Q, C1s and c1r bind to the antibody and lead to phagocytosis and inflammation

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18
Q

What are the two ways complement fixing works?

A

➝ formation of MAC (membrane attack complexes) which punches holes in the tumor cells -lysing them
➝ antibodies can also form complexes with the complement (complement fixing) which leads to phagocytosis

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19
Q

How many classes of antibodies are there?

A

➝ 5

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20
Q

What determines antibody class?

A

➝ the difference in the heavy chain

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21
Q

What are 3 properties of IgG?

A

➝ 4 heavy chain domains

➝ stabilised by two disulfide bonds in between the heavy chains

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22
Q

What are disulfide bonds formed between?

A

➝ Two cysteine residues of amino acid

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23
Q

How is IgD different from IgG?

A

➝ it has a longer hinge that is stabilised by one disulfide bond

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24
Q

How many domains does IgE have?

A

➝ 5 domains

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25
Q

How is IgA different to IgG?

A

➝ similar but the third CH3 domain has a modification which allows interaction with the J chain so the two monomers can join together
➝ wrapped by secretory components to be secreted into the mucus

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26
Q

What is IgM similar to?

A

➝ IgD

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27
Q

How many domains does IgM have and how can it form a pentamer?

A

➝ 5 domains

➝ forms a pentamer with the help of the J chain

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28
Q

What is the function of IgM?

A

➝ Fixes complement

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29
Q

What is the heavy chain of IgM?

A

➝ Mu

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30
Q

What is the heavy chain of IgD?

A

➝ delta

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31
Q

What is the heavy chain of IgG?

A

➝ gamma

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32
Q

What is the heavy chain of IgA?

A

➝ alpha

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33
Q

What is the heavy chain of IgE?

A

➝ epsilon

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34
Q

Which Ig has the heaviest molecular weight and why?

A

➝ IgM

➝ it forms a pentamer

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35
Q

Which 2 Igs fix complement?

A

➝ IgM

➝ IgG

36
Q

Which Ig crosses the placenta?

A

➝ IgG

37
Q

What does the Fc on IgG bind to?

A

➝ phagocytes

38
Q

What does the Fc on IgE bind to?

A

➝ mast cells

➝ Basophils

39
Q

What is the function of IgM?

A

➝ forms immune complexes and fixes complement

➝ monomer serves as BCR

40
Q

What is the function of IgD?

A

➝ BCR that indicates mature B cells

41
Q

What is the only antibody that is not secreted?

A

➝ IgD

42
Q

What is the function of IgG?

A

➝ Neutralises toxins

➝ opsonisation

43
Q

What is the main antibody of the primary response?

A

➝ IgM

44
Q

What is the main antibody of the secondary response?

A

➝ IgG

45
Q

Where is IgA secreted into?

A

➝ mucus
➝ tears
➝ saliva
➝ colostrum

46
Q

What is the function of IgE?

A

➝ allergy

➝ anti-parasites

47
Q

What is the default Ig produced by B cells?

A

➝ IgM

48
Q

Describe how B cells differentiate into plasma and memory cells from VDJ recombination?

A

1) after VDJ recombination of B cells they become mature circulating B cells
2) the lymphoid progenitor stem cell in the bone marrow gives rise to T cells
3) The T cells migrate to the thymus and undergo similar VDJ recombination to form TCR
4) the T cells receive signals from APC and become activated and activate B cells when pathogens are there
5) the B cell migrates into the germinal center for affinity maturation
6) in the dark zone clonal expansion occurs, then somatic hypermutation
7) selection occurs in the light zone
8) the B cells undergo the cycle between the light and dark zone many times and they undergo class switching
9) then they differentiate to plasma and memory cells and circulate

49
Q

What is affinity maturation?

A

➝ honing of the variable fragment to the particular pathogen

50
Q

What occurs in the dark zone?

A

➝ Clonal expansion

➝ Somatic hypermutation

51
Q

What is somatic hypermutation?

A

➝ an enzyme creating mutations in the DNA

52
Q

What is clonal expansion?

A

➝ the B cell makes clones of itself

53
Q

What occurs in the light zone?

A

➝ Selection

54
Q

Where are the light and dark zone found?

A

➝ Germinal center in the spleen or lymph node

55
Q

What is the cycle through the light and dark zone called?

A

➝ Affinity maturation

56
Q

What are the two stages of B cell activation?

A

➝ T cell independent

➝ T cell dependent

57
Q

What happens in the T cell independent stage?

A

➝ When the B cell encounters the antigens it undergoes clonal expansion
➝ Some of them differentiate into IgM secreting plasma cells

58
Q

What happens in the T cell dependent stage?

A

➝ Some B cell clones migrate into the lymph nodes
➝ The B cell needs to recognise the antigens, internalise them and then present them with MHC class II
➝ the B cell needs to be activated by the TCR (the T cell has to have been activated by the same pathogen)
➝ The CD40 and CD40L join
➝ The T helper cell produces cytokines to complete the 3 step verification process

59
Q

What does differentiation and clonal expansion of activated B cells require?

A

➝ Antigen binding to BCR
➝ co-stimulation by activated Th cell specific to the same antigen
➝ Th cell-derived cytokines

60
Q

How many unique B cells does the VDJ recombination produce?

A

➝ 1 billion B cells with unique B cell receptors

61
Q

How does clonal expansion occur?

A

➝ When a pathogen invades the body the B cell receptor with the closest binding to the pathogen gets activated
➝ it will make more clones of itself
➝ The clones migrate to the germinal center for affinity maturation

62
Q

Describe affinity maturation?

A

➝ the naive B cell that has been activated by a T cell enters the dark zone of the germinal center and undergoes clonal expansion
➝ the enzyme AID makes point mutations in the variable regions of B cells at random points
➝ after AID the B cells are all unique - somatic hypermutation
➝ the B cells migrate into the light zone to undergo selection
➝ the FDC presents the antigens on its surface
➝ the B cells will compete to bind to the FDC
➝ the B cells with high affinity bind and present the antigens to the Tfh cell which sends a survival signal
➝ B cells with reduced affinity undergo apoptosis because there is no survival signal from Tfh
➝ this is repeated for several cycles until the affinity is high enough

63
Q

Where does affinity maturation occur?

A

➝ In the germinal center at the periphery of the T cell zone

64
Q

What two types of cell assist with affinity maturation?

A

➝ Follicular dendritic cells

➝ T follicular helper cells

65
Q

What is the function of follicular dendritic cells?

A

➝ They stay in the germinal center and present antigens for the selection process
➝ not normal dendritic cells

66
Q

What can T follicular helper cells do that other T cells cannot?

A

➝ Enter the germinal center

67
Q

How is major heavy chain class switching done?

A

➝ DNA recombination

68
Q

How is minor heavy chain class switching done?

A

➝ mRNA differential splicing

69
Q

What is major heavy chain class switching?

A

➝ IgM to IgG, IgA and IgE

➝ IgG to IgA and IgE

70
Q

What is minor class switching between?

A

➝ IgM and IgD

71
Q

What three cytokine signals are needed for IgG1 and what cells produce them?

A

➝ Increased IL-4 - TH2
➝ Decreased IFN gamma - TH1
➝ Increased IL-10 - Treg

72
Q

What 4 cytokine signals are needed for IgG3 and what cells produce them?

A

➝ decreased IL-4 - TH2
➝ Increased IFN gamma - TH1
➝ Decreased TGF beta - Treg
➝ increased IL-10 - Treg

73
Q

What cytokine signal is needed for IgG4 and what cell produces it?

A

➝ increased IL-4 - TH2

74
Q

What two cytokine signals are needed for IgA and what cells produce it?

A

➝ increased IL-5 - TH2

➝ Increased TGF beta - Treg

75
Q

What two cytokine signals are needed for IgE and what cells produce it?

A

➝ Increased IL-4 - TH2

➝ decreased IFN gamma - TH1

76
Q

How does cytokine signalling occur?

A

➝ CD40L on T cells interacts with CD40 on B cells

77
Q

What are the 3 steps for class switch recombination to occur?

A

1) cytokine signal
2) switch signals
3) AID and DSB repair proteins

78
Q

Where does class switching proceed and why?

A

➝ Only downstream because the segments are removed

➝ you cannot switch to something β€˜behind’ you

79
Q

What can IgM switch to?

A

➝ IgG
➝ IgA
➝ IgE

80
Q

What can IgG switch to?

A

➝ IgA

➝ IgE

81
Q

How are unneeded classes cut out?

A

➝ Enzymes turn the unneeded segments into loops and they are cut out
➝ the mRNA no longer contains the other regions

82
Q

What is the difference between membrane bound and secreted Ig?

A

➝ the secreted form has a tail piece

➝ the membrane bound has an anchor made up of a hydrophobic transmembrane region and a cytoplasmic tail

83
Q

Describe how differential splicing of ΞΌ constant regions occurs?

A

➝ the VDJ is not changed
➝ the C μ region is made up of μ1, μ2, μ3 and μ4, a secreted region, a stop codon, a poly A site
➝ followed by a membrane M1, M2 region, a stop codon and a poly-A site
➝ for secreted heavy chains the DNA region is transcribed and spliced at the first poly-A site so the membrane regions are not transcribed

84
Q

What does BCR binding lead to?

A

➝ activation of tyrosine kinase

➝ signal transduction pathway for cell proliferation, differentiation and survival

85
Q

What is the BCR that initially binds the antigen called?

A

➝ a low affinity antibody

π“˜π“‚π“‚π“Šπ“ƒπ‘œπ“π‘œπ‘”π“Ž (14 decks)

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