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Immunology 2.0 > Lecture 8: Lymphocyte Development and Antigen Receptor Gene Rearrangement > Flashcards

Lecture 8: Lymphocyte Development and Antigen Receptor Gene Rearrangement Flashcards

1
Q

where does sequential and ordered rearrangement of Ag receptor genes and the expression of antigen receptor proteins occur

A

Generative Lymphoid organs

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2
Q

What are the transcription factors that cause a common lymphoid progenitor cell to differentiate into Pro-B cells

A

EBF, E2A, and Pax5

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3
Q

What are the transcription factors that cause a common lymphoid progenitor cell to differentiate into T cell precursor cells

A

Notch 1 and GATA3

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4
Q

Pro-B cells differentiate into

A
  • Follicular (FO) B cells
  • Marginal zone (MZ) B cells
  • B-1 cells
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5
Q

In the thymus, stromal cells produce ____ that drives the proliferation of human T cell progenitors

A

IL-7

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6
Q

The development of NK cells is dependent on ____

A

IL-15

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7
Q

In developing B cells the ______ locus opens up and becomes accessible to the proteins that will mediate Ig gene rearrangement and expression

A

Ig heavy chain

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8
Q

In developing alpha/beta T cells the ______ opens up and becomes accessible for TCR gene rearrangement and expression

A

TCR beta gene locus

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9
Q

EBF, E2A, and Pax-5 transcription factors that induce the

A
  • expression of genes required for B cell development
  • these include genes encoding:
    • Rag-1 and Rag-2
      • proteins regulating the BCR rearrangment
    • The surrogate light chains (pre-B cell receptor)
    • The Igalpha and Igbeta signaling proteins of the B cell receptor complex
    • the Igalpha and Igbeta signaling proteins of the B cell receptor complex
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10
Q

DNA methylation of certain cytosine residues generally ____ genes

A

silences

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11
Q

_____ are a class of small noncoding RNAs (about 22 nucleotides) 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)

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12
Q

What is allelic exlusion

A
  • Individuals codominantly inherit maternal and paternal sets of alleles for L and H chains
  • however, only one of the VLCL and VHCH alleles (either maternal or parental) is expressed in a single B cell
  • This is also the case in TCR
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13
Q

Stem cell (a precursor of both T and B cells) contains germline __ and ___

A

Ig and TCR

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14
Q

what are the 3 mechanisms of rearrangement of DNA to form variable regions of chains in T and B cells

A
  • Somatic recombination
  • mRNA splicing
  • Juncitonal diversity
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15
Q
A
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16
Q

The H-chain of Ig polypeptide is on chromosome

A

14

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17
Q

The k-chain of Ig polypeptide is on chromosome

A

2

18
Q

The gamma chain of Ig polypeptide is on chromosome

A

22

19
Q

The heavy chain of B cell has __ separate gene sements in chromosome 14

A

4 (V, D, J, C)

20
Q

____ and ___ encode ezymes performing recombination of BCR and TCR during the process of VDJ recombination

A

RAG1 and RAG2 (Recombination-activating genes 1 and 2)

21
Q

The cellular expression of RAG1 and RAG2 is restricted to B and T lymphocytes during

A

their developmental stages (makes sense because you don’t want VDJ recombination later in life-cycle)

22
Q

The proceess of V(D)J recombination generates a repertoire of different TCR _____ and BCR ____ molecules for recognition of various microbial antigens

but the inaccuracies of joining achieved by junctional diversity further increases the diversity of TCRs ___ and BCRs ___

A
  • TCR (3x106)
  • BCR (106)
  • but the inaccuracies of joining achieved by junctional diversity further increases the diversity of TCRs (1016)and BCRs (1011)
23
Q
A
24
Q
A
25
Q

BCR recombination occurs in what order

A
  • First, D and J are chosen and DNA between them is deleted
  • Seond, V segment is chosen and DNA between V and DJ is deleted
  • Lastly, J is chosen and DNA between VDJ and C is deleted
26
Q

The largest contribution to the diversity of antigen receptors is made by the

A

removal or addition of nucleotides at the junctions of the V and D, D and J, or V and J segments at the time these segments are joined (junctional diversity)

27
Q

When are the checkpoints in lymphocyte development

A
  • Checkpoint #1: is after the production of the first polypeptide chain of the two-chain Ag receptor is completed
  • Checkpoint #2: follows the production of the second polypeptide chain of the Ag receptor is completed
28
Q

Pre-Ag receptors contain only one polypeptide chain present in the mature Ag receptor: name them

A
  • Pre-BCRs: contain Ig u heavy chain
  • Pre-TCRs: contian the TCR beta chain
  • (this makes sense because they are the first to be rearranged in there respective lineages)
  • note that it is the assembled pre-BCRs and pre-TCRs that provide signals for survival, proliferation, and further development of early B and T lineage cells
29
Q

Most B cells that develop from fetal liver-derived stem cells differentiate into the ___ lineage

A

B-1

30
Q

B lymphocytes that arise from bone marrow precursors after birth give rise to the -___ lineage

A
  • B-2
  • The affinity fo the BCRs for self Ags may contribute to differentiation of B-2 cells into:
    • Follicular B-2 cells: which are recirculating lymphocytes
    • Marginal zone B-2 cells: which are abundant in the spleen and also found in LNs
31
Q

Why do B-1 cells express a limited BCR diversity

A
  • because Tdt is not expressed in the fetal liver
    • Tdt (Terminal deoxynucleotidyl transferase) is an enzyme that adds 20 non-template-encoded nucleotides called N nucleotides
32
Q

The large numbers of B-1 cells are found as self-renewing population in the ___ and _____ sites

A

peritoneum and mucosal sites

33
Q

B-1 cells spontaneously secrete ___ Abs that often react with microbial polysaccharides and lipids as well as oxidized lipids

A
  • IgM
  • Thes Abs are sometimes called natural antibodies because they are present in individuals without overt immunization
  • B-1 cells contribute most of the serum IgM during the early phases of infection
34
Q

Marginal zone (MZ) B cells localize to the _____ and respond to ____

A
  • splenic marginal zone
  • and respond to blood-borne Ags
35
Q

following rearrangement of their BCR chain genes and removal of autoreactive cells via central tolerance, immature B-2 cells relocate to the

A

spleen

36
Q

Follicular B cells respond to ____ Ags in a ______ manner, and progressively undergo immunoglobulin ________ and _____

A

Follicular B cells respond to protein Ags in a T cell-dependent manner, and progressively undergo immunoglobulin isotype switching and affinity maturation

37
Q

Only mature ______ upon T-cell dependent activation develop into long-lived plasma cells or memory B cells

A

Follicular B-2 cells

38
Q

similar to B-1 cells, MZ B cells

A

have BCRs fo limited diversity which respond to polysaccaride Ags and generate natural Abs

39
Q

MZ B cells respond very rapidly to ____ and differentiate into

A

Marginal zone B cells respond very rapidly to blood-born microbes and differentiate into short-lived IgM-secreting plasma cells

40
Q

Explain gamma/delta T cells are developed instead of alpha/beta T cells from the Progenitor-T cells

A
  • The Rearrangement of TCR beta, gamma (or delta) loci is initiated simultaneously
  • if a cell first succeeds in productively rearranging its TCR gamma or TCR delta loci before it makes a producitive TCR beta rearrangement, it is selected into the gamma/delta T cell lineage
41
Q

Why is there a limited diversity of gamma/delta TCRs

A

becuase only a few of the available V, D, and J segments are used in mature Gamma/delta T cells

Immunology 2.0 (25 decks)

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