Lecture 8: Lymphocyte Development and Antigen Receptor Gene Rearrangement Flashcards Preview

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

Flashcards in Lecture 8: Lymphocyte Development and Antigen Receptor Gene Rearrangement Deck (41):
1

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

Generative Lymphoid organs 

2

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

EBF, E2A, and Pax5

3

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

Notch 1 and GATA3

4

Pro-B cells differentiate into

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

5

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

IL-7

6

The development of NK cells is dependent on ____

IL-15

7

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

Ig heavy chain

8

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

TCR beta gene locus 

9

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

  • 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 

10

DNA methylation of certain cytosine residues generally ____ genes 

silences

11

_____ 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)

microRNAs (miRs) 

12

What is allelic exlusion

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

13

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

Ig and TCR

14

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

  • Somatic recombination
  • mRNA splicing
  • Juncitonal diversity

15

16

The H-chain of Ig polypeptide is on chromosome 

14

17

The k-chain of Ig polypeptide is on chromosome

2

18

The gamma chain of Ig polypeptide is on chromosome

22

19

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

4 (V, D, J, C) 

20

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

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

21

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

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

22

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 ___

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

23

24

25

BCR recombination occurs in what order

  • 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

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

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

When are the checkpoints in lymphocyte development

  • 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

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

  • 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

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

B-1

30

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

  • 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

Why do B-1 cells express a limited BCR diversity

  • 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

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

peritoneum and mucosal sites

33

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

  • 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

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

  • splenic marginal zone
  • and respond to blood-borne Ags

35

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

spleen 

36

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

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

37

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

Follicular B-2 cells 

38

similar to B-1 cells, MZ B cells 

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

39

MZ B cells respond very rapidly to ____ and differentiate into 

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

40

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

  • 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

Why is there a limited diversity of gamma/delta TCRs

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