B Cells Flashcards

1
Q

What are the 4 main effector functions of antibodies?

A

1-B Cell receptors
2-Neutralization
3-Opsonization
4-Signaling

*theoretic 1 x 10^16 and practical 1 x 10^9 diversity

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2
Q

What are the 3 main sources of diversity for antibodies?

A

1-Genetic diversity
2-Juncitonal diversity
3-Somatic hypermutation

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3
Q

What are the 5 antibody isotypes?

A
1-IgG (y)
2-IgM (u)
3-IgD (δ)
4-IgA (a)
5-IgE (ε)
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4
Q

What are the two main multimeric complexes?

A

1-Pentameric IgM
2-Dimeric IgA

*both contain J chains

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5
Q

Which isotype primarily functions to activate complement system but also transports across epithelium and neutralizes?

A

IgM

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6
Q

Which Isotype functions to sensitize basophils?

A

IgD

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7
Q

Which isotype primarily functions to neutralize, opsonize, activate complement, transport across placenta, diffusion into extravascular sites and also sensitizes mast cells and NK cells?

A

IgG

*IgG1, IgG2, IgG3, IgG4 in this category

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8
Q

Which isotype primarily functions to neutralize, transport across epithelium (dimer), diffuse into extravascular site (monomer) and also can activate complement and opsonization?

A

IgA

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9
Q

Which isotype primarily functions to sensitize mast cells but can sensitize basophils as well as diffuse into extravascular sites

A

IgE

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10
Q

Gene rearrangement happens in the _______ while somatic hypermutation and isotype switching happens in __________

A

Bone marrow, secondary lymphoid organs and circulation

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11
Q

What determines the antibody class?

A

Heavy chain

*Interacts with antigen and well as receptor, proportionally small variable region

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12
Q

What part of the antibody binds antigen, has proportionally large variable region and two isotypes (κ, λ)?

A

Light chain

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13
Q

The antigen binding region is called the _____ region and crystallizable/constant region is called_______?

A

Fab, Fc

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14
Q

What are 4 antibody antigen epitopes?

A

1-Terminal polysaccharide
2-Polysaccharide chain
3-globular protein surface
4-globular protein pocket

*can be linear, discontinues, multivalent

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15
Q

What creates antibody coding sequence?

A

Somatic recombination

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16
Q

What complex recognizes 7 or 9 bp recombination signal sequences to randomly pair gene segments in B cells?

A

RAG complex

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17
Q

After RAG cleaves the heptameter RSS and forms the D and J gene segments and opens the DNA hairpins, what enzyme adds the N-nucleotide segment to form the coding joint?

A

TdT- Terminal deoxynucleotidyl transferase

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18
Q

Though IgM is first expressed and then IgD, which antibodies can B cells express?

A

All types, however the isotype switch is permanent. They can be membrane bound or soluble as well

*express IgM/IgD until activated

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19
Q

Which 5 changes in immunoglobulin genes during B cell life are irreversible?

A
1-V-region assembly from gene fragments
2-Generation of junctional diversity
3-Assembly of transcriptional controlling elements
4-Somatic Hypermutation
5-Isotype switching
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20
Q

Which two changes in immunoglobulin genes during a B cells life are reversible and regulated?

A

1-Transcription activated with coexpression of surface IgM and IgD
2-Synthesis changes from membrane Ig to secreted antibody

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21
Q

Multiple antibodies targeted against the same antigen is called what?

A

Polyclonal

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22
Q

A single antibody targeted against a single antigen is called what?

A

Monoclonal

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23
Q

What are three diagnostic uses for antibodies?

A

1-Pathogen identification
2-Protein quantification
3-Cellular identification

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24
Q

What are 3 therapeutic uses for antibodies?

A

1-Targeted killing
2-Chemical delivery
3-Immunomodulatory

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25
Q

Antibodies bind _______ epitope but may bind _______antigens

A

One, Many

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26
Q

Strength of physical interaction between antibody and epitope is called?

A

Affinity

27
Q

Overall strength of antigen binding is called?

A

Avidity

28
Q

Which CD is present in a pluripotent hematopoietic stem cell?

A

CD 34

29
Q

Which CD activates common lymphoid progenitor cells?

A

CD 10

30
Q

Which CD activates B-cell precursor cells?

A

CD 127 (is an IL-7a receptor)

31
Q

Which CD activates Pro-B cells?

A

CD 19 (is an A B cell co-receptor)

32
Q

Where are the two checkpoints in B cell development?

A

1-Between Late Pro-B cell and Large Pre-B cell

2-Between Small Pre-B and immature B cell

33
Q

During the Pro-B cell stages there is ______ immunoglobulin, during Pre-B cell stages there is _________ and in immature B cell stage there is ___________ immunoglobulin

A

No, Heavy chain, Functional

34
Q

What cells do B cells interact with in bone marrow during development?

A

Stromal cells

35
Q

Which three adhesion/signaling molecules are present in the Lymphoid progenitor cell with stromal cells?

A
  • CAMs
  • VLA-4
  • VCAM-1
36
Q

Which two adhesion/signaling molecules are present in the Early pro-B cell interaction with stromal cells?

A
  • Kit
  • SCF

*Turn on RAGs

37
Q

Which main signaling molecule is present in the late pro-B cell interaction with stromal cells?

A

IL-7 receptor interacting with IL-7

38
Q

Which two adhesion/signaling molecules are present in the pre-B cell interaction with stromal cells?

A
  • CAMs

- IL-7

39
Q

D-J rearrangements on both chromosomes for the heavy-chain gene are always productive and take place during which stage?

A

Early Pro-B cell stage

40
Q

V-DJ rearrangement on the first chromosome for the heavy chain either survives or moves on to the second chromosome during which stage?

A

Late pro-B cell

50% of B cells survive

41
Q

Pre-B cell receptor expression is the _______ checkpoint in B cell maturation

A

First

42
Q

IgB stops RAGS, degrades heavy chain RAG complexes, changes heavy chain chromatin, and drives what?

A

Allelic exclusion

43
Q

Expressed in the ER, which receptor is key in determining heavy chain requirements and works with Iga and IgB signaling components?

A

Pre-B cell receptor

44
Q

What 3 things happen between Large and small Pre-B cell stages?

A

1-100 small Pre-B cells
2-RAG genes reactivated
3-Unique recombination per cell

45
Q

What is the order of the four chances of product rearrangement or Light chain genes in Pre-B cells?

A

1-k gene on first chromosome
2-k gene on second chromosome
3-λ gene on first chromosome
4-λ gene on second chromosome

46
Q

Which growth factor receptor is active during early pro-B cell stage and the beginning of late pro-B cell stage?

A

Kit

47
Q

Which growth factor receptor is active during early pro-B cell stage until the end of Large pre-B cell stage?

A

IL-7 receptor

48
Q

Which lymphoid-specific recombinases are active during late pro-B cell and Large Pre-B cell stages then turns off and is active again during Small Pre-B cell and immature B cells stages?

A

RAG-1 and -2

49
Q

Which surrogate light chain component is active during early pro-B cell until the Small Pre-B cell stages?

A

λ5 and VpreB

50
Q

What is the order of the 7 B cell maturity stages?

A
1-Stem cell
2-Early Pro-B cell
3-Late Pro-B cell
4-Large Pre-B cell
5-Small Pre-B cell
6-Immature B cell
7-Mature B cell
51
Q

Which signal transduction proteins are active beginning in the early Pro-B cell stage all through Mature B cell?

A

Iga and IgB

52
Q

Which signal transduction protein is active from the end of early pro-B cell until the beginning of Mature B cell stages?

A

CD19 (is a B cell co-receptor)

53
Q

Exposure to self antigen, ensuring tolerance is called what?

A

negative selection

54
Q

What are the two types of tolerance?

A
  • Central tolerance (in bone marrow)

- Peripheral tolerance (peripheral organs/lymph nodes)

55
Q

What are the three fates of strong binding in negative selection for antibodies?

A

1-Light chain reorganization
2-Apoptosis (if receptor is self-reactive)
3-Anergy (signaled to make IgD and becomes non-responsive)

56
Q

What are three secondary lymphoid tissues?

A

1-Spleen
2-Lymph nodes
3-GALT

57
Q

B cells enter a lymph node through what?

A

High endothelial venule

58
Q

What attracts immature B cells to HEV?

A

Chemokine CCL21

59
Q

CCL21 and which other chemokine attracts B cells into the lymph node?

A

CCL19

60
Q

Which chemokine attracts B cells into the primary follicle?

A

CXCL13

61
Q

Interaction with follicular dendrite cells and cytokines drive what?

A

Maturation of immature B cells

62
Q

What are the 4 stages of B cell activation in lymphoid tissue?

A

1-Antigen exposure in cortex
2-Interaction with T cells (T-cell area)
3-Migration, secondary lymphoid follicle formation and clonal expansion (in germinal center)
4-Plasma cell production and antibody secretion

63
Q

Dysfunctional B cells can cause what?

A

Cancer