B lymphocytes Flashcards

1
Q

B lymphocytes are the precursors of what important cells that produce antibodies?

A

Plasma cells

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2
Q

All antigen-unstimulated B lymphocytes have what two immunoglobins in their plasmalemma?

A

IgM and IgD

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3
Q

Can B lymphocytes bind anitgens without MHC proteins?

A

Yes

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4
Q

Each B lymphocyte is specific for how many antigens?

A

one

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5
Q

True or false: B cell are genetically engineered and produced only when exposed to antigens

A

False-B cell clones reactive to >109 antigens exist in the body at all times, without the need for exposure to these antigens.

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6
Q

How long does the primary response take?

A

7-10 days

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7
Q

Which antibody type is produced in the greatest amount in the primary response?

A

IgM

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8
Q

How long does a secondary immune response take place?

A

2-3 days

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9
Q

Which antibody is produced in the greatest amount in the secondary immune response?

A

IgG

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10
Q

Is the overall antibody count higher or lower in secondary immune responses?

A

Higher

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11
Q

What happens to the affinity of antibodies the longer an infectious process occurs?

A

Gets more specific, and binds better

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12
Q

What is the cell that is the precursor to all blood cells?

A

Stem cells

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13
Q

DO stem cells conduct immunoglobin production?

A

No

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14
Q

What are the 5 stages of B cell maturation?

A
  1. Stem cell
  2. Pre-B cell
  3. Immature B cell
  4. Mature B cell
  5. Activated B cell
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15
Q

Are pre-B cells responsive to antigen?

A

No

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16
Q

Pre-B cells do not have mature immunogoblin yet, but what do they have?

A

cytoplasmic mu-heavy chains, which will eventually become membrane-bound IgM

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17
Q

In what stage do antigens become expressed on the surface of B cells?

A

Immature B cell stage

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18
Q

What antigen(s) is/are present in the immature B cell stage?

A

IgM

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19
Q

What happens to immature b cells if they encounter an antigen? Why do they do this?

A

Death, to prevent reaction to self proteins

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20
Q

At which stage in B cell development are the cells outside the bone marrow?

A

Mature B cell stage

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21
Q

Mature B cells express two antibodies on their membrane. Which class of immunoglobins are they from?

A

IgM and IgD

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22
Q

Are the IgM and IgD antigens on mature B cells specific for the same or different antigens?

A

The same–bad if not

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23
Q

What happens when B cells encounter an antigen that is specific for its receptor?

A

Activation/Mitosis

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24
Q

True or false: a high level of antigens are produced, but are of low specificity when B cells are initially activated

A

False–both low amounts, and low specificity

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25
Q

During which stage of B cell development can heavy chain isotype switching occur?

A

At the activated B cell stage

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26
Q

True or false: switching of light chains never occurs in the activated B cell stage

A

True

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27
Q

What are the two major cell types that B cells can differentiate into?

A

Plasma cells or memory cells

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28
Q

Where are memory B cells found?

A

Recirculate through secondary lymphoid tissue throughout their life

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29
Q

What specific antibodies do plasma cells secrete?

A

one of the heavy chain isotypes (IgG, IgM, IgA or IgE).

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30
Q

Where are plasma cells found?

A

in lymphoid organs and bone marrow and not generally in the peripheral blood.

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31
Q

What are the histological features of plasma cells?

A

Elongated cell, eccentric nucleus, abundant cytoplasm, and perinuclear halo.

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32
Q

How many antibodies can be secreted per second by plasma cells?

A

3000-4000

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33
Q

What percent of protein synthesis of plasma cells are devoted to antibody generation

A

Up to 40%

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34
Q

How do B and T cells react together?

A

B cells present antigen bits to T cells via CD4+/class II MHC

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35
Q

Do B and T cells that cooperate together respond to the same antigen?

A

Usually different

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36
Q

What is the time frame for antigen presentation from B cells?

A

1-6 hours

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37
Q

Can nonprotein antigens be complexed to MHC proteins for T cell activation?

A

Nope

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38
Q

True or false: The epitope that the B cell binds is usually different from what is presented to T-helper cells.

A

True

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39
Q

What happens when B and T lymphocytes interact?

A

B and T cells express costimulatory proteins on their cell surface that must interact in order to get T lymphocyte activation and the consequent B lymphocyte activation leading to antibody production.

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40
Q

What are the proteins that B cells produce that aid interact with T cells? What is the protein that T cells express for this?

A

B7 and CD40 which interact with the T cell protein CD28 and CD40L respectively

41
Q

When B7:CD28 and CD40L:CD40 interactions occur along with the binding of class II MHC-bound peptide through the T cell antigen receptor, what happens?

A

T cells are activated and release cytokines that, along with CD40L:CD40 interactions, activate B cells to differentiate into antibody-producing plasma cells.

42
Q

How do B cells compareto macrophages in terms of their ability to process antigens?

A

Less efficient due to less lysosomes, but they are more specific

43
Q

What do B cells require to respond to antigens?

A

Th lymphocytes

44
Q

What are the “thymus dependent” antigens?

A

Ones that respond to proteins, and require the use of T helper cells

45
Q

What are thymus independent antigens?

A

B cells responses to non-protein antigens, and thus cannot utilize helper T cells

46
Q

What are the two types of TI antigens?

A

TI 1

TI 2

47
Q

What are TI-1 antigens?

A

Antigens that bind to non-immunoglobin receptors on B cells, and promote polyclonal expansion

48
Q

What are TI-2 antigens?

A

Antigens that bind through B cell surface immunoglobin, and activate antigen specific B cells

49
Q

What does not occur with TI antigens that does occur with TD antigens?

A
  1. memory cell generation
  2. isotype switching
  3. affinity maturation occurs.
50
Q

LPS is an example of what type of TI antigen? What does this complex associate with?

A

TI-1

associates with B cell surface CD14 and Toll-like receptor-4

51
Q

Antigens that crosslink B cell surface immunoglobulin signal B cell activation through what proteins?

A

Igα and Igβ

52
Q

What is the function of Igα and Igβ in B cells?

A

Functions the same as CD3 proteins in T cells

53
Q

How many of each chain type comprise each antibody isotope?

A

two heavy chains (of one of the five isotypes) and either two kappa or two lambda light chains.

54
Q

True or false: the kappa light chain, lambda light chain, and heavy chain are each encoded by different chromosomes

A

True

55
Q

What are the V regions of immunoglobin genes? Where are they found?

A

V= Variable regions at the 5’ end of each string. Signal genes here encode a protein sequence used to guide a protein to the ER.

56
Q

What are 3’ to the V regions, and within the heavy chain and kappa kight chain loci?

A

J (“joining”) regions

57
Q

What is located between the V and J regions of the genome?

A

Heavy chain D regions

58
Q

Where are the C (constant) regions of immunoglobin found?

A

at the 3’ end of each heavy and light chain string of gene segments

59
Q

The variable region of the immunoglobulin heavy chain forms what part of the antibody?

A

antigen binding site

60
Q

The variable region of the heavy chain gene is generated by which segments?

A

generated by assembling V, D, and J segments of DNA.

61
Q

The variable region of the light chain genes are generated by assembling what segments of DNA?

A

V and J (no D like heavy has)

62
Q

What are the four main mechanisms that account for the diversity seen in the immunoglobin repertoire?

A
  1. Combinatinoal diversity
  2. Junctional diversity
  3. Heavy and light chain combining
  4. Somatic point mutations
63
Q

What is combinational diversity?

A

Different copies of gene segments exist that can be rearranged in many ways.

64
Q

What is junctional diversity?

A

Nucleotide addition and removal occurs at the joints between gene segments that are recombined.

65
Q

What is the normal configuration of the imunoglobin genes that are found in every nucleated cell throughout the body, except in B cells?

A

Germline DNA

66
Q

What is recombinase, and what is its function in B cell development?

A

It causes the looping out of DNA sections followed by excision of the intervening sequences, and ligation of the DNA.

67
Q

What is the gene that encodes recombinase? Mutations in this gene leads to what?

A

RAG1 and RAG2

SCID results if there are mutations

68
Q

What ensures that the progeny of a B cell will not mutate and express a different Ig gene?

A

Genes are irreversibly lost in development

69
Q

Which rearranges first: the heavy or the light chain locus?

A

Heavy chain

70
Q

What is the first step in rearranging the heavy chain locus?

A

Randomly chosen D and J segments are brought together, with intervening sequences deleted

71
Q

What happens in heavy gene rearrangement, after D and J segments are brought together?

A

V region gene segment is randomly sleected, and placed 5’ to the DJ segment. Intervening segment is deleted

72
Q

What is the function of the enzyme terminal deoxynucleotidyl transferase (TdT)? Where does it act?

A

Randomly adds nucleotides in the joint region between gene segments in the VDJ region

73
Q

What separates the VDJ segment from the first C region gene (C-mew)?

A

An intron region

74
Q

Translation of the mRNA gives rise to cytoplasmic -heavy chain protein occurs in what stage of B cell maturation?

A

Pre-B cell stage

75
Q

If the rearrangement of the 1st heavy chain gene is nonproductive, what happens?

A

The other allele is used

76
Q

If both rearrangements of heavy chain are nonproductive what happens?

A

Apoptosis

77
Q

What is the first step in light chain gene rearrangement?

A

A V region gene segment is randomly selected and placed next to a J region gene segment to form a VJ segment, with intervening sequences being subsequently deleted.

78
Q

What happens in light chain gene rearragement after a VJ segment is created?

A

Splicing out introns

79
Q

What separates the VJ segment of the light chain, from the C region?

A

An intron

80
Q

An excess of kappa light chains might suggest that the patient has what?

A

a B cell tumor that is producing a large amount of monoclonal antibody utilizing a kappa light chain or some other type of nonmalignant lymphoproliferative disorder.

81
Q

What is allelic exclusion?

A

if the 1st rearrangement is productive then genes on other chromosome won’t be rearranged

82
Q

Why is there no “choosing” of constant regions in light chain gene recombination, like there is in heavy?

A

Kappa and lambda light chain gene segments are located on different chromosomes

Heavy chain located on same, so can splice out which ones not needed

83
Q

What are the antibodies that are expressed on resting B cells?

A

IgM and IgD

84
Q

The primary RNA transcript for the IgM and IgD antibodies present on the surface of B cells has which regions? How does this contribute to the anitbody expression o the cell?

A

VDJ regions coupled to both C(mew) and C(delta) region

Thus splicing can splice out one of the C regions but retain the VDJ segment

85
Q

How do antibodies that are expressed on the cell surface of B cells become secreted?

A

the transmembrane and cytosolic sequences are spliced out of the primary RNA transcript

86
Q

What is the first step the B cell takes in switching antibody isotypes?

A

Stimulation by antigens

87
Q

How can gene splicing lead to isotype switching in B cells?

A

A long primary RNA transcript containing VDJ regions connected to many or all CH genes is produced, followed by alternative RNA splicing.

88
Q

How can gene deletion lead to isotype switching in B cells?

A

deletion of intervening CH region genes to align VDJ regions with a particular CH gene occurs

89
Q

What are switch regions in the DNA segment?

A

Regions that allow DNA recombination to occur between heavy chain constant region gene segments

90
Q

What determines which antibody a B cell will switch to?

A

The array of T cell cytokines to which the B cell is exposed

91
Q

IL-4 cytokines induce B cells to switch to what antibody? IL-5?

A

IL-4 = IgE

IL-5 = IgA

92
Q

Antibodies in a secondary immune response have a (higher or lower) average affinity than those in a primary immune response.

A

Higher

93
Q

What alters the affinity of antibodies in a secondary immune response?

A

small somatic mutations in the V region genes to alter the strength of binding of an antibody

94
Q

Are C regions changed when antibodies increase in affinity?

A

No

95
Q

Why is secondary immune response much more sensitive to stimulation?

A

memory B cells express a higher affinity antigen receptor

96
Q

How are B cells that express higher affinity anitbodies selected for?

A

their increased ability to bind antigen increases their chance of stimulation by follicular helper T cells (TFH), leading them to out compete other B cell types

97
Q

If a B cell receives interferon gamma, which antibodies will it produce?

A

IgG1 and IgG3

98
Q

If a B cell receives IL-4, what antibodies will it produce?

A

IgE IgG4