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Immunology > Lymphocyte Development and Antigen Receptor Gene Rearrangement Part I (Lec 10) > Flashcards

Lymphocyte Development and Antigen Receptor Gene Rearrangement Part I (Lec 10) Flashcards

1
Q

What are the series of events that occur during maturation of B and T lymphocytes?

A
  1. Commitment of progenitor cells to the B lymphoid or T lymphoid lineage
  2. proliferation
  3. sequential and ordered rearrangement of Ag receptor genes
  4. selection events
  5. differentiation of B and T cells
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2
Q

Hematopoietic stem cells (HSCs) give rise to what?

A

common lymphoid progenitor (CLP)

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3
Q

CLPs give rise to what?

A

B cells, T cells and NK cells

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4
Q

Pro-B cells can eventually differentiation into what?

A

follicular B cells, marginal zone B cells, B-1 cells

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5
Q

Pro-T cells may commit to what?

A

alpha beta T cells

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6
Q

What does commitment to the B or T lineage depend on?

A

sequential signaling from several cell surface receptors

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7
Q

What happens to H chain in developing B cells?

A

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

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8
Q

What happens to the TCR beta gene locus in developing B cells

A

it opens up and becomes accessible for TCR gene rearrangement and expression

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9
Q

The Notch-1 and GATA-3 transcription factors commit developing lymphocyte to T cell or B cell lineage?

A

T cell

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10
Q

The Notch family of proteins are cell surface molecules that are ___ ____when they interact with specific ligands on neighboring cells

A

proteolytically cleaved

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11
Q

The cleaved intracellular portions of Notch proteins migrate to the nucleus and do what?

A

modulate the expression of specific target genes

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12
Q

Notch-1 together with GATA3 induces expression of genes involved with what?

A

development of alpha beta T cells

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13
Q

What are the transcription factors that induce expression of genes required for B cell development?

A

EBF, E2A, and Pax-5

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14
Q

What are the specific genes required for B cell development and what do they code for?

A

Rag1 and Rag2: BCR arrangement

surrogate L chains: pre-B cell receptor

Ig alpha and Ig beta proteins: the B cell receptor

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15
Q

Proliferation ensures that a large pool of ___ cells is available for generation of a highly diversity of mature lymphocytes

A

progenitor

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16
Q

In regards to proliferation and development of T cells, if a pre-Ag receptor is successfully rearranged, it will provide what?

A

survival signals that select the cell

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17
Q

In regards to proliferation and development of T cells, IL-7 produced by ____ cells in the thymus drives the proliferation of human T cell progenitors

A

stromal

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18
Q

Mutations in the common y chain shared by type I cytokines receptors for IL-2, IL-7 and IL-15 block in T cell and NK cell development that results in what?

A

an immunoddeficiency disorder in human

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19
Q

IL-15 is required for what?

A

development of NK cells

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20
Q

The mechanisms that make genes available or unavailable in chromatin are considered to be ____ mechanisms

A

epigenetic

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21
Q

DNA methylation usually does what to genes?

A

silences them

22
Q

CD4 vs CD8 lineage commitment involves chromatin modifications that place the CD4 gene where?

A

into an inaccessible heterochromatin state

23
Q

miRNAs modulate gene expression during what?

A

T cell development

24
Q

Deletion of Dicer, a key enzyme in miRNA generation, in the T lineage results in what?

A

preferential loss of regulatory T cells

25
Q

The loss of Dicer in the B lineage results in a block at the what?

A

pro-B to pre-Bcell transition

26
Q

miR17-92 plays a key role in preventing what?

A

apoptosis of pre-B cells by inhibiting the expression of Bim

27
Q

miR-150 targets what?

A

a Notch receptor that plays important roles both in proliferation, differentiation, and survival of T cells

28
Q

Individuals codominantly inherit maternal and paternal sets of alleles for L and H chains. Only one of the Vl Cl and VhCh alleles is expressed in a single B cell. This restriction is termed what?

A

allelic exclusion

note: allelic exclusion also governs the expression of TCR

29
Q

True or false?

A single B cell has 2 chromosomes encoding Vh and Vl chains - maternal and paternal

A

true

30
Q

Three unlinked gene groups encode immunoglobulins. Within each of these genes, there are multiple coding regions which recombine at the level of DNA to yield a binding site. What chromosomes are the genes that code for H chain, k chain, and lambda chain on?

A

H chain: 14
k chain: 2
lambda chain: 22

31
Q

RAG1 and RAG2 encode enzymes performing recombination of BCR and TCR during what process?

A

VDJ recombination

32
Q

The cellular expression of RAG1 and RAG2 is restricted to what cells?

A

B and T lymphocytes during their developmental stages

33
Q

In regards to how BCR diversity is achieved, each chromosome encoding the components of BCR is trying to be what?

A

the first in genes’ rearrangement

34
Q

In regards to how BCR diversity is achieved, heavy chain has 4 separate gene segments in chromosome 14: V, D, J, and C; these segments contain what?

A

multiple copies of each segment

35
Q

True or False?
In regards to how BCR diversity is achieved, in a single B cell all copies but one are randomly deleted giving a unique combination of V-D-J. Each B cell generates its own V-D-J sequence and thus all B cells are different

A

true

36
Q

In regards to how BCR diversity is achieved, which segments are chosen first, second, etc. : V, D, or J?

A

D and J are chosen and DNA in between them is deleted, then the V segment is chosen and DNA is deleted again. Next J is chosen and DNA in-between is deleted once again.

37
Q

In regards to how BCR diversity is achieved, when productive rearrangement is confirmed, the process is over and recombination is stopped. How is this done?

A

It remains unknown

38
Q

In regards to how BCR diversity is achieved, If the Vh rearrangement is productive, then the B cell does what?

A

proliferates for a while and “takes care” of the Vl

39
Q

Junctional diversity results from what?

A

the loss of nucleotides through the action of exonuclease(s) and from the addition of N and P nucleotides

40
Q

What are P nucleotides derived from?

A

the asymmetric opening of hairpin loops

41
Q

What leads to P nucleotides’ palindromic appearance?

A

self-complementarity

42
Q

In regards to selection process, during lymphocyte development, the cells go through numerous checkpoints at which the developing cells are tested and continue to mature only if a preceding step in the process has been successfully completed. When does the first checkpoint occur? Second checkpoint?

A

1st checkpoint: after the production of the first polypeptide chain of the two-chain Ag receptor is completed

2nd checkpoint: after the production of the second polypeptide chain of the two-chain Ag receptor is completed

43
Q

Pre-Ag receptors and Ag receptors deliver what type of signals for their proliferation and continued maturation??

A

survival

44
Q

Pre-Ag receptors are called pre-BCRs in B cells and they contain how many of the two polypeptide chains present in a mature Ag receptor?

A

only one

45
Q

Pre-BCRs contain what chain?

A

the Ig u H chain

46
Q

Pre-TCRs contain what chain?

A

the TCR beta chain

47
Q

In regards to positive selection after the first checkpoint, what happens to potentially harmful T cells and B cells that strongly recognize self Ags?

A

potentially harmful T cells: eliminated by apoptosis

potentially harmful B cells: induced to rearrange their second chain of Ag receptors again

48
Q

In T cell lineage, what does positive selection ensure?

A

the maturation of CD8 and CD4 T cells whose receptors recognize appropriate self MHC molecules

49
Q

T cells positively selected by self MHC molecules in the ___ are able to recognize foreign Ags displayed by the same MHC molecules on APCs in peripheral tissues

A

thymus

50
Q

When does negative selection occur?

A

shortly after Ag receptors are first expressed on developing B and T cells

51
Q

What does negative selection do to T cells and B cells whose Ag receptors bind strongly to self Ags present in the thymus or bone marrow?

A

eliminates T cells by apoptosis

alters B cell by inducing further Ig gene rearrangements

52
Q

Negative selection of immature lymphocytes is an important mechanism for maintaining what?

A

the central tolerance to many self Ags

Immunology (12 decks)

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