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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
The loss of Dicer in the B lineage results in a block at the what?
pro-B to pre-Bcell transition
26
miR17-92 plays a key role in preventing what?
apoptosis of pre-B cells by inhibiting the expression of Bim
27
miR-150 targets what?
a Notch receptor that plays important roles both in proliferation, differentiation, and survival of T cells
28
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?
allelic exclusion note: allelic exclusion also governs the expression of TCR
29
True or false? | A single B cell has 2 chromosomes encoding Vh and Vl chains - maternal and paternal
true
30
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?
H chain: 14 k chain: 2 lambda chain: 22
31
RAG1 and RAG2 encode enzymes performing recombination of BCR and TCR during what process?
VDJ recombination
32
The cellular expression of RAG1 and RAG2 is restricted to what cells?
B and T lymphocytes during their developmental stages
33
In regards to how BCR diversity is achieved, each chromosome encoding the components of BCR is trying to be what?
the first in genes' rearrangement
34
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?
multiple copies of each segment
35
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
true
36
In regards to how BCR diversity is achieved, which segments are chosen first, second, etc. : V, D, or J?
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
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?
It remains unknown
38
In regards to how BCR diversity is achieved, If the Vh rearrangement is productive, then the B cell does what?
proliferates for a while and "takes care" of the Vl
39
Junctional diversity results from what?
the loss of nucleotides through the action of exonuclease(s) and from the addition of N and P nucleotides
40
What are P nucleotides derived from?
the asymmetric opening of hairpin loops
41
What leads to P nucleotides' palindromic appearance?
self-complementarity
42
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?
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
Pre-Ag receptors and Ag receptors deliver what type of signals for their proliferation and continued maturation??
survival
44
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?
only one
45
Pre-BCRs contain what chain?
the Ig u H chain
46
Pre-TCRs contain what chain?
the TCR beta chain
47
In regards to positive selection after the first checkpoint, what happens to potentially harmful T cells and B cells that strongly recognize self Ags?
potentially harmful T cells: eliminated by apoptosis potentially harmful B cells: induced to rearrange their second chain of Ag receptors again
48
In T cell lineage, what does positive selection ensure?
the maturation of CD8 and CD4 T cells whose receptors recognize appropriate self MHC molecules
49
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
thymus
50
When does negative selection occur?
shortly after Ag receptors are first expressed on developing B and T cells
51
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?
eliminates T cells by apoptosis | alters B cell by inducing further Ig gene rearrangements
52
Negative selection of immature lymphocytes is an important mechanism for maintaining what?
the central tolerance to many self Ags

Immunology (12 decks)

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