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Flashcards in B lymphocytes Deck (98):
1

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

Plasma cells

2

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

IgM and IgD

3

Can B lymphocytes bind anitgens without MHC proteins?

Yes

4

Each B lymphocyte is specific for how many antigens?

one

5

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

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

6

How long does the primary response take?

7-10 days

7

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

IgM

8

How long does a secondary immune response take place?

2-3 days

9

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

IgG

10

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

Higher

11

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

Gets more specific, and binds better

12

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

Stem cells

13

DO stem cells conduct immunoglobin production?

No

14

What are the 5 stages of B cell maturation?

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

15

Are pre-B cells responsive to antigen?

No

16

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

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

17

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

Immature B cell stage

18

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

IgM

19

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

Death, to prevent reaction to self proteins

20

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

Mature B cell stage

21

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

IgM and IgD

22

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

The same--bad if not

23

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

Activation/Mitosis

24

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

False--both low amounts, and low specificity

25

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

At the activated B cell stage

26

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

True

27

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

Plasma cells or memory cells

28

Where are memory B cells found?

Recirculate through secondary lymphoid tissue throughout their life

29

What specific antibodies do plasma cells secrete?

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

30

Where are plasma cells found?

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

31

What are the histological features of plasma cells?

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

32

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

3000-4000

33

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

Up to 40%

34

How do B and T cells react together?

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

35

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

Usually different

36

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

1-6 hours

37

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

Nope

38

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

True

39

What happens when B and T lymphocytes interact?

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.

40

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

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

41

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?

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

42

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

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

43

What do B cells require to respond to antigens?

Th lymphocytes

44

What are the "thymus dependent" antigens?

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

45

What are thymus independent antigens?

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

46

What are the two types of TI antigens?

TI 1
TI 2

47

What are TI-1 antigens?

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

48

What are TI-2 antigens?

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

49

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

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

50

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

TI-1

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

51

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

Igα and Igβ

52

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

Functions the same as CD3 proteins in T cells

53

How many of each chain type comprise each antibody isotope?

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

54

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

True

55

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

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

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

J ("joining") regions

57

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

Heavy chain D regions

58

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

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

59

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

antigen binding site

60

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

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

61

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

V and J (no D like heavy has)

62

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

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

63

What is combinational diversity?

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

64

What is junctional diversity?

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

65

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

Germline DNA

66

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

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

67

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

RAG1 and RAG2


SCID results if there are mutations

68

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

Genes are irreversibly lost in development

69

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

Heavy chain

70

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

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

71

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

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

72

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

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

73

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

An intron region

74

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

Pre-B cell stage

75

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

The other allele is used

76

If both rearrangements of heavy chain are nonproductive what happens?

Apoptosis

77

What is the first step in light chain gene rearrangement?

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

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

Splicing out introns

79

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

An intron

80

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

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

What is allelic exclusion?

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

82

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

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

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

IgM and IgD

84

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?

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

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

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

86

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

Stimulation by antigens

87

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

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

88

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

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

89

What are switch regions in the DNA segment?

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

90

What determines which antibody a B cell will switch to?

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

91

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

IL-4 = IgE

IL-5 = IgA

92

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

Higher

93

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

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

94

Are C regions changed when antibodies increase in affinity?

No

95

Why is secondary immune response much more sensitive to stimulation?

memory B cells express a higher affinity antigen receptor

96

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

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

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

IgG1 and IgG3

98

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

IgE IgG4