Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Immunology - Unit 2 - Zach H. > Lymphocyte Development and Antigen Receptor Gene Rearrangement > Flashcards

Lymphocyte Development and Antigen Receptor Gene Rearrangement Flashcards

1
Q

The maturation of B and T lymphocytes involves a series of events that occur in the generative lymphoid organs. What are these events in order?

A
  • Commitment of progenitor cells to the B lymphoid or T lymphoid lineage.
  • Proliferation of progenitors and immature lymphocytes (providing a large pool of cells for generation of lymphocytes).
  • Sequential and ordered rearrangement of Ag receptor genes and the expression of antigen receptor proteins.
  • Selection events (eliminate potentially dangerous self-reactive cells).
  • Differentiation of B and T cells into functionally and phenotypically distinct subpopulations.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What do pluripotent stem cells give rise to?

A

Distinct B and T lineasges

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What type of cell does hematopoietic stem cells (HSCs) give rise to?

A

Common Lymphoid Progenitor (CLP)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Which three types of cells do CLPs give rise to?

A
  • B cells
  • T cells
  • NK cells
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What drives the commitment to different lineages of CLPs?

A

transcription factors

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What cell types can Pro-B cells eventually differentiate into?

A
  • Follicular (FO) B cells
  • Marginal zone (MZ) B cells
  • B-1 cells
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What cell types can Pro-T cells commit to?

A
  • alpha-beta T cells
  • gamma-delta T cells
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What stimulates the proliferation of the committed T and B cell progenitors?

A

cytokines

* IL-7 for T cell progenitors

* Unknown for B cell progenitors

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Why is proliferation of B and T cell progenitors so important?

A

Proliferation ensures that a large pool of progenitor cells is available for generation of a high diversity of mature lymphocytes.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What happens if a pre-Ag receptor is successfully rearranged?

A

It provides survival signals that select the cell.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

In the thymus, which cell type produces IL-7 to drive proliferation of human T cell progenitors?

A

Stromal Cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What cytokine is the development of NK cells dependent on?

A

IL-15

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

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

A

Sequential signaling from several cell surface receptors.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

You know that the commitment to the B or T cell lineage is dependent on sequential signaling from several cell surface receptors. What does this signaling activate?

A

Activates transcription factors that contribute to the commitment via induction of gene expression and rearrangements of Ag receptor gene.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What are the two ways in which activated transcription factors contribute to the commitment of the B or T cell lineage?

A
  • gene expression of Ag receptor gene
  • rearrangements of Ag receptor gene
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

In developing B cells, what happens to the Ig heavy chain locus?

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

In developing alpha-beta T cells, what happens to the TCR ß gene?

A

TCR ß gene locus opens up and becomes accessible for TCR gene rearrangement and expression.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

What transcription factors commit developing lymphocytes to the T cell lineage?

A
  • Notch-1
  • GATA-3
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

What are Notch family of proteins?

A

Cell surface molecules that are proteolytically cleaved when they interact with specific ligands on neighboring cells.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

How does the Motch protein modulate expression of specific target genes?

A

The cleaved intracellular portion of Notch protein migrates to the nucleus and modulates the expression of specific target genes.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Which T cell type does GATA3 induce the expressionf genes for?

A

alpha-beta T cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

True or False:

Some genes (which encode the components of pre-TCR) undergo V(D)J recombination.

A

True

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

Which transcription factors induce the expression of genes required for B cell development?

A
  • EBF
  • E2A
  • Pax-5
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

Which proteins regulate BCR rearrangement?

A
  • Rag-1
  • Rag-2
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

What do EBF, E2A, and Pax-5 transcription factors include genes encoding for what?

A
  • Rag-1 and Rag-2 proteins regulating the BCR rearrangement
  • The surrogate light chains (pre-B cell receptor)
  • The Ig-alpha and Ig-beta signaling proteins of the B cell receptor complex
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

What does DNA methylation on cytosine residues generally do?

A

Silences Genes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

What do non-coding RNAs do to gene expression?

A

silence gene expression

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

What do epigenetic mechanisms do in lymphocyte development?

A

Make genes available or unavailable in chromatin.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

True or False:

The structural organization of portions of chromosomes makes some genes available for transcription factors to initiate the transcription.

A

True

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

What is a class of small noncoding RNAs (22 NT) that control gene expression at the post-transcriptional level by impairing translation or by promoting degradation of the target messenger RNA (mRNA)?

A

microRNAs (miRs)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

Does allelic exclusion govern the expression of TCR?

A

Yes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

You know that individuals codoninantly inherit maternal and parental sets of alleles for L and H chains. But how is VLCL and VHCH alleles of the maternal or parental expressed in a single B cell?

A

ONLY one of the VLCL and VHCH alleles (either maternal or parental) is expressed in a single B cell.

33
Q

Are maternal and parental allotpes expressed equally?

A

Yes - the maternal and parental allotypes are expressed equally since there are many B cells and T cells.

34
Q

How are the variable regions of the chains in T and B cells determined?

A

By rearrangement of the DNA.

35
Q

What is the major mechanism of epitope-specific diversity of BCR and TCR?

A

DNA chromosomal rearrangement.

36
Q

What are the 3 different DNA chromosomal rearrangement mechanisms that determine epitope-specific diversity of BCR and TCR?

A
  • somatic recombination
  • mRNA splicing
  • junctional diversity

** The process includes deletion of DNA/RNA nucleotides and reannealing gene segments. **

37
Q

What do stem cells (a precursor of both T and B cells) contain?

A
  • germline Ig
  • TCR
38
Q

True or False:

In achieving BCR diversity, each chromosome (maternal and parental) encoding the components of BCR is trying to be the first in genes’ rearrangement.

A

True

39
Q

What are the 4 heavy chain separate gene segments on chromosome 14?

A
  • “V” - variable
  • “D” - diversity
  • “J” - joining
  • “C”- constant
40
Q

Fill in the Blank:

In a single B cell all copies but _____ are randomly _____ giving a unique comination of __-__-__. Each B cell generates it’s own V-D-J sequence and thus all B cells are different.

A

one; deleted; V-D-J

41
Q

What are Rag-1 and Rag-2 proteins?

A

The recombination-activating genes 1 and 2 which encode enzymes performing recombination of BCR and TCR during the process of VDJ recombination.

42
Q

When is the cellular expression of RAG1 and RAG2 restricted?

A

The cellular expression of RAG1 and RAG2 is restricted to B and T lymphocytes during their developmental stages.

43
Q

List the steps showing how BCR diversity is achieved.

A
  • First, D and J are chosen and DNA in between them is deleted.
  • Second, V segment is chosen and DNA between V and DJ is deleted.
  • Next, J is chosen and DNA between VDJ and C is deleted (CM for IgM and CD for IgD).
  • The chance to produce a “productive rearrangement” (without stop codons in the sequence) is about 10%.
  • There will be a test (transcription + translation) for selection of “productive rearrangement”.
  • When “productive rearrangement” is confirmed - the “competition” is over and the recombination of other segments is STOPPED.
  • How it is done remains unknown.
44
Q

If the VH rearrangement is productive, then what happens?

A

B cell proliferates for a while and “takes care” of the VL.

* there will be a second test for selection of “productive rearrangement”, this time for the VL chain *

* the recombination rules are the same for VL chain *

45
Q

What is the final result after the first and second “productive rearragement” test have been performed?

A

Each B cell produces only one kind of VH and VL.

46
Q

How are B cells able to recognize any Ag possible?

A

Because the number of combinations possible is very big, B cells produced can recognize any Ag possible.

47
Q

In BCR diversity, does the light chain have any D segments?

A

NO

48
Q

You know that the process of V(D)J recombination generates a repertoire of different TCR (3x106) and BCR (1x106) molecules for recognition of various microbial antigens and that this V(D)J recombination alone is not enough to produce a huge variety of TCRs and BCRs which would recognize all antigens possible. How is further specificity obtained?

A

JUNCTIONAL DIVERSITY further increases the diversity of TCRs (1x1016) and BCRs (1x1011).

49
Q

Where is juctional diversity generated?

A

generated at the points between the joining genes

50
Q

What does junctional diversity result from?

A

Results from THE LOSS of nucleotides through the action of exonuclease(s) and from THE ADDITION of N and P nucleotides.

51
Q

What type of opening in the DNA generates P nucleotides?

A

An asymmetric opening of hairpin loops generates P nucleotides.

52
Q

What is unique about P nucleotides that lead to their palindromic appearance and their name?

A

Self-complementarity of P nucleotides leads their palindromic appearance and to their name.

53
Q

What does the opening of the hairpin loops produce?

A

Opening of the hairpin loops produces short, self-complementary single stranded extensions that can be incorporated into junctions, or can be removed via an exonuclease activity.

54
Q

Which protein cleaves hairpin loops and adds P nucleotides?

A

RAG proteins

55
Q

After RAG proteins have cleaves hairpin loops and adds P nucleotides, which protein adds nucleotides to connect the DNA?

A

Terminal Deoxynucleotidyl Transferase (TdT)

56
Q

Why is the selection process important?

A

Selection process eliminates potentially harmful self-reactive lymphocytes.

57
Q

What do the critical checkpoints in the selection process ensure?

A

Ensure that only LYMPHOCYTES that have sucessfully completed Ag receptor gene rearrangement processes are selected to mature.

58
Q

During the selection process, when does checkpoint #1 occur?

A

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

59
Q

During the selection process, when does checkpoint #2 occur?

A

Follows the production of the second polypeptide chain after the Ag receptor is completed.

60
Q

True or False:

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.

A

True

61
Q

What chain does the pre-BCRs contain?

A

Ig µ heavy chain

62
Q

What chain does the pre-TCRs contain?

A

TCR ß chain

63
Q

What do pre-Ag and Ag receptors deliver for the proliferation and continued maturation for pre-BCRs and pre-TCRs?

A

survival signals

64
Q

True or False:

The pre-Ag receptors contain only one polypeptide chain present in a mature Ag receptor.

A

True

65
Q

What is the first Ig chain for the Ag receptor gene to be completely rearranged in B cells?

A

Ig Heavy Chain (IgH)

66
Q

What is the next step after developing B cells successfully rearrange their Ig heavy chain genes?

A

Express the µ heavy chain protein and assemble the pre-BCR.

67
Q

What is synthesized due to the developing T cells that make a productive TCR ß chain gene rearrangement?

A

The TCR ß chain protein and assemble the pre-TCR.

68
Q

What percentage of developing B and T cells make productive in-frame rearrangements of Ag receptor gene (capable of generating a protein)?

A

30%

69
Q

What happens if developing B and T cells make a out-of-frame rearrangement?

A

The pre-Ag receptors are not expressed, the cells do not receive survival signals and undergo apoptosis.

70
Q

What do assembled pre-BCRs and pre-TCRs provide signals for?

A
  • survival
  • proliferation
  • further development of early B and T lineage cells
71
Q

B and T lymphocytes with what proceed to express genes encoding the second chain of the BCR or TCR?

A

FUNICTIONAL pre-Ag receptors

72
Q

If B or T lymphocytes make productive rearrangements of the 2nd chain, do they express the complete Ag receptor while they are immature or mature?

A

immature

73
Q

Through what process are lymphocytes that express useful Ag receptors preserved by?

A

Positive Selection

74
Q

True or False:

T cells positively selected by self MHC molecules in the thymus are able to recognize foreign Ag displayed by the same self MHC molecules (class I MHC or class II MHC, respectively).

A

True

75
Q

What is the difference between how potentially harmful T or B cells that strongly recognize self Ags are handled in positive selection?

A
  • Harmful T cells that strongly recognize self Ags -> eliminated by apoptosis.
  • Harmful B cells that strongly recognize self Ags -> induced to rearrange their 2nd chain of Ag receptors again.
76
Q

How are lymphocytes that express useful Ag receptors are preserved by what process?

A

Positive Selection

77
Q

What does positive selection of T cells ensure?

A

The maturation of CD8 or CD4 T cells whose receptors don’t recognize self-Ags but can recognize MHC molecules (class I MHC or class II MHC, respectively).

78
Q

True or False:

T cell positively selected by self MHC molecules in the thymus are able to recognize foreign Ag displayed by the same self MHC molecules on APCs in peripheral tissues.

A

True

79
Q
A

Immunology - Unit 2 - Zach H. (3 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions