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Immuno Exam Block 2 :) > Lecture 10: Lymphocyte Development and Antigen Receptor Gene Rearrangement > Flashcards

Lecture 10: Lymphocyte Development and Antigen Receptor Gene Rearrangement Flashcards

1
Q

Hematopoietic stem cells give rise to ___ which give rise to

A

Common lymphoid progenitors CLPs which give rise to B cells, T cells and NK cells

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2
Q

What happens when Pre-Ag receptor is successfully rearranged

A

It provides survival signals that select the cell

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3
Q

What drives the proliferation of human T cell progenitors and where is it produced

A

IL-7 produced in the thymus

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4
Q

What other function does IL-7 have besides proliferation of T cells

A

When produced by stromal cells in bone arrow, it promotes B cell development

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5
Q

What drives development of NK cells and where

A

IL-15 in the thymus

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6
Q

First step in developing B cells

A

The Ig heavy chain locus opens up and becomes accessible to proteins that will mediate Ig gene rearrangement and expression

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7
Q

First step in developing a/b T cells

A

The TCR beta gene locus opens up and becomes accessible for TCR gene rearrangement and expression

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8
Q

Which transcription factors commit cells to the T cell lineage

A

Notch-1 and GATA-3

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9
Q

Function of Notch protein

A

Notch is cleaved and intracellular portion travels to nucleus to modulate expression of target genes
GATA3 also helps induce this expression

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10
Q

Which proteins regulate TCR/BCR rearrangement

A

Rag-1 and Rag-2

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11
Q

Which genes undergo V(D)J recombination

A

Those which encode the components of pre-TCR

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12
Q

Which TFs induce expression of genes for B cell development

A

EBF, E2A and Pax-5

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13
Q

DNA methylation on cytosine results in

A

Gene silencing

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14
Q

Allelic exclusion refers to

A

The restriction that only one of the light chain and heavy chain alleles (maternal or paternal) is expressed in a single B cells

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15
Q

Variable regions of the chains in T and B cells are determined by

A

Rearrangement of the DNA

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16
Q

What is the major mechanism of epitope-specific diversity of BCR/TCRs

A

DNA chromosomal rearrangement

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17
Q

The process of rearrangement includes

A

Deletions of DNA/RNA nucleotides and reannealing gene segments.
This is done by Rag1 and Rag2 recombination enzymes and is called V(D)J recombination

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18
Q

RAG-mediated DNA breaks are repaired exclusively by

A

Non homologous end joining

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19
Q

Three mechanisms of rearranging gene segments

A

Somatic recombination
mRNA splicing
Junctional diversity

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20
Q

How does each B cell generate unique combinations of V(D)J segments

A

In a single B cell all copies but one each of VDJ are randomly deleted

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21
Q

Recombination starts with which chain in B and T cells, respectively, and then moves to which chain

A

Starts with heavy chain in B cells
Starts with Beta chain in T cells
If functional, rearrangement of light chain (B cells) or alpha-chain (T cells) occurs

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22
Q

Achieving BCR diversity heavy chain step one

A

First, D and J are chosen and DNA between them is deleted

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23
Q

Achieving BCR diversity heavy chain step two

A

Second, a V segment is chosen and DNA between V and DJ is deleted

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24
Q

Achieving BCR diversity heavy chain step three

A

Third, a C is chosen and DNA between VDJ and C is deleted

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25
Q

What is the chance % of producing a productive rearrangement (w/o stop codons in sequence)

A

10%

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26
Q

H-chain chromosome
K-chain chromosome
Lambda-chain chromosome

A

H-14
K-2
L-22

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27
Q

THE VDJ rearrangement segment facilitates the synthesis of _________, and is controlled by ______

A

Facilitates synthesis of a Mu or delta heavy chain, controlled by alternative mRNA splicing
This then associates with lightchain forming IgM or IgD molecule

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28
Q

Non-IgM/IgD heavy chains are produced by ______, which is a process that

A

Class-switch recombination (CSR), a process that exchanges the constant region of the heavy chain

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29
Q

Class switch recombination (CSR) requires what enzyme that is only expressed at what time

A

AID- only expressed in activated B cells

30
Q

AID method of operation

A

AID introduces uracil residues into DNA of S (switch) regions, inducing generation of DNA breaks at these regions followed by repair

31
Q

Junctional diversity

A

TdT and/or RAG adds or removes nucleotides to the exposed ends of the V, (D) or J genes before they are reunited

32
Q

Junctional diversity is helpful how

A

It increases the diversity of TCRs and BCRs

33
Q

Junctional diversity is created where

A

At the points between joining genes

34
Q

Junctional diversity results from

A

The loss of nucleotides through action of exonucleases and the addition of N and P nucleotides

35
Q

RAG and TdT function in junctional diversity

A

RAG cleaves hairpin loops and adds P nucleotides (P nucleotides form from asymmetric opening of hairpin)
TdT adds N nucleotides

36
Q

Checkpoint #1 of the selection process

A

After the production of the first polypeptide chain of the two-chain Ag receptor is completed

37
Q

Checkpoint #2 of the selection process

A

Follows the production of the second polypeptide chain of the Ag receptor

38
Q

Pre-Ag receptor structure

A

Pre-Ag receptors contain only one polypeptide chain present in mature Ag receptor and a surrogate receptor chain

39
Q

Pre-BCRs contain

A

Ig(Mu) heavy chain

40
Q

Pre-TCRs contain

A

TCR Beta chain

41
Q

What is the first Ag receptor gene to be completely rearranged in B cells

A

Ig heavy chain

42
Q

Developing B cells that successfully rearrange their Ig heavy chain genes then express

A

The Mu heavy chain protein and assemble the pre-BCR

43
Q

Developing T cells that make productive TCR B chain gene rearrangement synthesize

A

The TCR B chain protein and assemble the pre-TCR

44
Q

What percent of B/T cells make a productive in-frame rearrangement

A

30%

45
Q

Assembled pre-BCRs/TCRs provide signals for

A

Survival, proliferation and further development of early B/T cell lineages

46
Q

Negative/positive selection is part of what checkpoint

A

Checkpoint 2

47
Q

If cells make productive rearrangement of second chain, they express

A

Complete Ag receptor while they are still immature. These cells will be positively selected

48
Q

What is important for maintaining the central tolerance to many self Ags

A

Negative selection

49
Q

When does negative selection occur

A

Shortly after Ag receptors are first expressed on developing B/T cells

50
Q

Negative selection effect on T cells vs B cells

A

It will eliminate harmful T cells but ALTER harmful b cells whose Ag receptors bind strongly to self Ags in thymus/bone marrow

51
Q

Clonal deletion

A

Process of eliminating harmful T cells

52
Q

Receptor editing

A

Second attempt at Ig gene rearrangement, if this fails, B cells will enter clonal deletion

53
Q

What chain will be altered first in a B cell that binds self Ags. What chain will be altered second?

A

Kappa Light chain will be rearranged first

Lambda light chain is rearranged second, if needed

54
Q

B cells developing from fetal liver-derived stem cells differentiate into

A

B-1 lineage

55
Q

B cells developing from bone marrow precursors give rise to

A

B-2 lineage

56
Q

B-1 cell receptor diversity

A

Limited BCR diversity because TdT is not expressed in the fetal liver
Without TdT- no junctional diversity

57
Q

B-1 cells are found where and secrete what

A

Found in peritoneum and mucosal sites

Spontaneously secrete IgM that react with polysaccharides/lipids/oxidized lipids

58
Q

B-1 B cell involvement in early phases of infection

A

Contribute most of the serum IgM during early phases

59
Q

Immature B-2 B cells relocate where after what

A

After rearrangement of BCR chain genes, they relocate to spleen

60
Q

B-2 cells can differentiate into

A

Marginal zone MZ B cells or Mature follicular FO B-2 cells

61
Q

FO B-2 cells are

A

Recirculating lymphocytes

62
Q

MZ B-2 cells are abundant where but also found where

A

Abundant in spleen (in marginal sinus), also found in lymph nodes

63
Q

MZ B cells respond to

A

Blood-borne pathogens

64
Q

Responses of MZ B cells are independent or dependent on T cell help

A

Independent of T cell help (usually) but can mediate SOME T cell dependent immune responses
They are self renewing

65
Q

FO B-2 cells may develop into plasma/memory cells depending upon

A

Mature FO B-2 cells depend upon T cell activation to mature into plasma/memory cells

66
Q

True or False - MZ B cells undergo immunoglobulin isotype switching and affinity maturation

A

Probably false? FO B-2 cells are the ones that do this because they respond to protein Ags in T cell dependent manner

67
Q

MZ B cell diversity

A

Similar to B-1 cells, they have limited diversity which respond to polysaccharide Ags and generate natural Abs

68
Q

MZ B cells respond very rapidly to ____ and differentiate into what

A

Respond rapidly to blood borne microbes and differentiate into short-lived IgM secreting plasma cells

69
Q

What causes the limited diversity of expressed gamma/delta TCRs

A

Only a few of the available V, D and J segments are used in mature yd T cells

70
Q

What determines T cell being yd or ab

A

If it first succeeds in rearranging its TCR y or delta loci before it makes a productive TCR beta rearrangement, it is selected to the yd T lineage
-happens about 10% of time

Immuno Exam Block 2 :) (22 decks)

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