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Immunology > lymphocyte development and antigen receptor gene rearrangement > Flashcards

lymphocyte development and antigen receptor gene rearrangement Flashcards

1
Q

B/T cell maturation

commitment:

TFs responsible for B cell commitment:

TFs responsible for T cell commitment:

A

activation of TFs shifting to pro-B/T cells

EBF, E2A, Pax-5

Notch-1 and GATA-3

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2
Q

B/T cell maturation

proliferation:

A

simulated by IL-7 in the bone marrow or thymus

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3
Q

B/T cell maturation:

selection:

A

survival of functional receptors that are not self-reactive

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4
Q

B/T cell maturation:

differentiation:

A

diversion into functional subgroups

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5
Q

hematopoietic stem cells → _____ → ____ , ____ , and ____

A

hematopoietic stem cells → common lymphoid progenitor → B cells (in bone marrow), T cells (in thymus), and NK cells (in bone marrow)

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6
Q

pro-B cells can eventually differentiate into:

1.

2.

3.

A
  1. FO B cells (follicular)
  2. MZ B cells (marginal zone)
  3. B-1 cells
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7
Q

Pro-T cells may commit to either:

1.

2.

A
  1. alpha-beta T cells
  2. gamma-delta T cells
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8
Q

commitment to different lineages is driven by

A

various TFs

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9
Q

proliferation of committed T and B cell progenitors is stimulated by

A

cytokines

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10
Q

_____ drives the proliferation of human T cell progenitors in the thymus and promotes B cell development in the bone marrow

A

IL-7 (produced by stromal cells)

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11
Q

the development of NK cells occurs in the ______ and it depends on ______

A

bone marrow

IL-15

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12
Q

early commitment to the B lineage:

first the Ig _____ chain locus opens up and becomes accessible to the proteins that will mediate Ig gene rearrangement and expression

A

heavy

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13
Q

early commitment to the T lineage: (alpha-beta T cells)

first the TCR ____ gene locus opens up and becomes accessible for TCR gene rearrangement and expression

A

beta

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14
Q

DNA methylation on ______ residues generall ______ genes

A

cytosine

silences

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15
Q

the modifications os histone tails of nucleosomes by post-translational _____ , ______ , or _____ render genes either active or inactive

A

acetylation, methylation, or ubiquitination

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16
Q

miRNAs are a class of small noncoding RNAs that control gene expression at the ______ level by impairing translation or by promoting degradation of the mRNA. miRNAs can also accumulate in the nuclei and regualte gene expression at the trascriptional level

A

post-transcriptional

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17
Q

individuals _____ inherit maternal and paternal sets of alleles for L and H chains of Ig molecules

however;

only one of the light chain and heavy chain alleles (either maternal or paternal) is _______ in a single B cell

this is called:

A

codominantly

expressed

allelic exclusion (similar for TCR)

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18
Q

the ______ regions of the chains in T and B cells are determined by rearrangement of the DNA

A

variable

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19
Q

DNA chromosomal rearrangement is the major mechanism of ____ ____ of BCR and TCR

A

epitope-specific diversity

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20
Q

3 mechanisms for BCR and TCR diversity:

1.

2.

3.

A
  1. somatic recombination - V (D) J combination
  2. junctional diversity (non-homologous end joining)
  3. mRNA splicing
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21
Q

BCR/TCR construction:

  1. BCR _____ chain and TCR _____ chain made first
  2. checks to make sure the first chain was made; _____ chain used
  3. BCR _____ chain and TCR _____ chain made second
  4. check to make sure that functional _____ chain was made
A
  1. heavy beta
  2. surrogate
  3. light alpha
  4. second
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22
Q

BCR/TCR genes:

  1. located on chromosome _____
  2. B cell heavy chain and T cell beta chains, consist of what segments:
  3. B cell light chain and T cell alpha chain, consist of what segments:
  4. each segment has multiple copies but all copies except one are _____ giving a unique combination
A
  1. 14
  2. (V)ariable, (D)iversity, (J)oining, and (C)onstant
  3. (V)ariable, (J)oining, and (C)onstant
  4. randomly deleted
23
Q

____ and ____ encode enzymes that perform recombination of BCR and TCR during the process of VDJ recombination

A

RAG1 and RAG2

24
Q

the cellular expression of RAG1 and RAG2 is restricted to B and T lymphocytes only during their ____ stages

A

developmental

25
Q

How is BCR diversity achieved:

  1. first ____ are chosen and DNA in between them is deleted
  2. second ____ segment is chosen and DNA between V and DJ is deleted
  3. third a _____ segment is chosen and DNA between VDJ and C is deleted
  4. there will be a test for slection of productive rearrangement with help of a:
  5. when productive rearrangement is confirmed, the competition between ____ and ____ heavy chain genes is over and the recombination of other segments is stopped
A
  1. D and J segments
  2. V segment
  3. C segment
  4. surrogate light chain
  5. maternal and paternal
26
Q

somatic recombination is the process of talking all the copies of the different sements and

A

choosing only one of each

(changes are made to the DNA itself)

27
Q

Rearrangement occurs in a specific order:

BCR heavy chain and TCR beta chain:

  1. ___ and ___ segments are chosen first, DNA between them is deleted
  2. ___ segment is chosen, DNA between it and DJ segment is deleted

BCR light chain and TCR alpha chain:

  1. ___ and ___ segments are chosen, DNA between them is deleted
A

BCR heavy chain and TCR beta chain:

  1. D and J segments
  2. V segment

BCR light chain and TCR alpha chain:

  1. V and J
28
Q

mRNA splicing:

  1. RNA transcript is made from _____ DNA
  2. alternative splicing of the ___ segments in BCR result in ____ and ____ variants of BCR
  3. this does not apply to ___ , ___ , or ___
A
  1. recombined
  2. C segments IgM and IgD
  3. IgG, IgA, or IgE
29
Q

junctional diversity:

  1. during rearragement, ___ ___ ___ are made in the DNA flanking chosen segment
  2. DNA strands are ligated via ___ with cosen segments now adjacent to each other
  3. new, novel ___ sequences are created
A
  1. double stranded breaks
  2. NHEJ
  3. DNA
30
Q

what is responsible for most of the diversity in BCR/TCR

A

junctional diversity

31
Q

___ creates asymmetric opening in hair pin loop of DNA

A

RAG

32
Q

gap between two ends (of cut DNA by RAG) is filled with random, untemplated sequence of nucleotides by ___

A

TdT

33
Q

selection:

  1. tests to ensure that ____ was actually produced (no out of frame rearrangements)
  2. final receptors don’t recognize ____
  3. final ___ recognize MHC I/II
  4. if any of these fail, cells
A
  1. chain
  2. self-Ag
  3. TCR

do not reeive required survial signals and will die

34
Q

first selection:

  1. BCR ___ chain and TCR ___ chain is tested
  2. ___ light chain and alpha chain are ued temporarily
  3. BCR heavy chain only uses ___ constant region (__) , delta not seen at this time
A
  1. heavy beta
  2. surrogate
  3. mu (IgM)
35
Q

second selection:

  1. BCR ___ chain and TCR ___ chain tested
  2. BCR heavy chain can use both ___ and ___ constant regions
  3. if functional BCR/TCR is made, cell undergoes ____ selection
A
  1. light alpha
  2. mu and delta
  3. positive/negative selection
36
Q

positive selection:

  1. completed TCR/BCR does not:
  2. TCRs must recognize ____
  3. these cells live on to become:
A
  1. self-Ag
  2. MHC
  3. immature B/T cells
37
Q

negative selection:

  1. completed TCR/BCR recognizes _____
  2. self-reactive TCRs undergo:
  3. self-reactive BCR undergoes:
  4. TCRs that don’t recognize ____ are deleted
  5. negative selection is responsbile for generating ____ ____
A
  1. self-Ag
  2. clonal deletion (by apoptosis)
  3. BCR editing
  4. MHCs
  5. central tolerance
38
Q

BCR editing:

  1. BCRs are initially made using the ___ chain
  2. if the B cell using the kappa chain is negatively selected, instead of undergoing clonal deletion, it tries again using the ___ chain
  3. after the lambda chain is recombined, it goes through the ____ round of selection again
  4. if ti fails this time, the B cell undergoes ___ ___ just like the T cell did
A
  1. kappa
  2. lambda
  3. second
  4. clonal deletion
39
Q

the VDJ rearrangement segment facilitates the synthesis of a ___ or ___ heavy chain controlled by ___ ___ ___ . this then associates with a light chain, thereby forming an ___ or ___ molecule, which is displayed on the cell-surface of a naive B cell

A

mu or delta

alternative mRNA splicing

IgM or IgD

40
Q

___ introduces a break in the DNA that is responsible for class-switch recombination to other Ig classes (other than IgM/IgD)

A

AID (activation-induced cytidine deaminase)

41
Q

AID is only expressed in

A

activated B cells

42
Q

RAG cleaves ___ and adds ___ nucleotides

A

hairpin loops

P

43
Q

TdT adds ___ nulceotides

A

N

44
Q

B-1 cells:

  1. are made it:
  2. no ___ and no ___ diversity
  3. reside in:
  4. only secrete ___
  5. ___ population
A
  1. fetal liver
  2. no TdT and no junction diversity
  3. peripheral tissues
  4. IgM
  5. self-renewing population
45
Q

B-2 cells:

  1. are made in:
  2. do have ___ and ___ diversity
  3. reside in:
  4. can produces all ___
A
  1. bone marrow
  2. have TdT and junctional diversity
  3. circuate in blood or reside in lymphoid organs
  4. isotypes
46
Q

B-2 cell subsets:

1.

2.

A
  1. FO B cells (follicular B cells)
  2. MZ B cells (marginal zone B cells)
47
Q

FO B cells characteristics:

1.

2.

3.

4.

A
  1. circulating population
  2. greater diversity, undergo affinity maturation
  3. mostly T cell dependent/isotype switched
  4. differentiate into long-lived plasma cells OR memory B cells
48
Q

MZ B cell characteristics:

1.

2.

3.

4.

A
  1. located in marginal zone of spleen or LNs
  2. less diversity
  3. mostly T cell-independent (IgM)
  4. differentiate into short lived plasma cells
49
Q

FO B2 cells respond to ____ Ags

A

protein

50
Q

FO B2 cells, upon T cell dependent activation, develop into

A

long lived plasma cells or memory B cells

51
Q

similar to B1 cells, MZ B cells have ___ diversity which resopnse to ___ Ags and generate ___ Abs

A

limited

polysaccharide

natural

52
Q

while the TCR beta chain is rearranging, the ___ and ___ are also rearranging

A

gamma chain and delta chain

53
Q

roughly ___ % of developing T cells become gamma/delta T cells

A

10

54
Q

gamma/delta T cells have very ___ diversity

A

limited

Immunology (23 decks)

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