Lecture 10 (Exam 2) Flashcards
The maturation of B and T lymphocytes involves a series of events that occur in the generative ________ organs.
Lymphoid
The maturation of lymphocytes requires a commitment of ________ cells to the B lymphoid or T lymphoid lineage.
Progenitor
The maturation of lymphocytes requires the proliferation of progenitors and (MATURE/IMMATURE) lymphocytes (providing a large pool of cells for generation of lymphocytes).
Immature
The maturation of lymphocytes requires sequential and ordered rearrangement of _____ receptor genes and the expression of BCR and TCR proteins.
Ag
The maturation of lymphocytes requires _______ events (eliminate potentially dangerous self-reactive cells).
Selection
The maturation of lymphocytes requires the _________ of B and T cells into functionally and phenotypically distinct subpopulations.
Differentiation
(MULTIPOTENT/PLURIPOTENT) stem cells give rise to distinct B and T lineages.
Pluripotent
Hematopoietic stem cells (HSCs) give rise to _______ _______ _______.
Common lymphoid progenitors (CLPs)
Common lymphoid progenitors (CLPs) give rise to what?
B cells
T cells
NK cells
The commitment to different lineages is driven by various…
Transcription factors
Pro-B cells can eventually differentiate into…
FO B cells (Follicular)
MZ B cells (Marginal zone)
B-1 cells
Pro-T cells may commit to either…
aB T cells (alpha/beta)
yd T cells (gamma/delta)
NK cells
Proliferation of the committed T and B cell progenitors is stimulated by _______, with _____ being most critical.
Cytokines
IL-7
Proliferation ensures that a large pool of progenitor cells is available for generation of a high ________ of mature lymphocytes.
Diversity
If a pre-Ag receptor is successfully rearranged, it provides ________ signals that select the cell.
Survival
In the thymus, _______ cells produce IL-7 that drives the proliferation of human T cell progenitors.
Stromal
Also, _____ produced by stromal cells in the bone marrow promotes B cell development at all stages of human life.
IL-7
The development of NK cells occurs in the thymus and it depends on ______.
IL-15
Early commitment to the B or T lineage depends on sequential signaling from several cell surface receptors. Signaling activates transcription factors that contribute to the commitment via induction of gene expression and rearrangements of _____ receptor gene.
Ag
First in developing B cells, the Ig (HEAVY/LIGHT) chain locus opens up and becomes accessible to the proteins that will mediate Ig gene rearrangement and expression.
Heavy
First in developing a/B T cells, the ______ gene locus opens up and becomes accessible for TCR gene rearrangement and expression.
TCR B (Beta)
The ______ and ______ transcription factors commit developing lymphocytes to the T cell lineage.
Notch-1
GATA-3
The ______ family of proteins are cell surface molecules that are proteolytically cleaved when they interact with specific ligands on neighboring cells. The cleaved intracellular portion of the protein migrates to the nucleus and modulates the expression of specific target genes.
Notch
The ______ also induces the expression of genes involved in development of aB T cells.
GATA-3
Some genes (which encode the components of pre-TCR) undergo _____ recombination.
V(D)J
The _____ and _____ proteins regulate the TCR and BCR rearrangement.
Rag-1
Rag-2
These transcription factors induce the expression of genes required for B cell development.
EBF (Early B cell factor)
E2A
Pax-5
The B cell transcription factors express genes encoding for _____ and _____ proteins regulating the BCR rearrangement, the ______ ______ ______ (pre-B cell receptor), and the _____ and _____ signaling proteins of the B cell receptor complex.
Rag-1 Rag-2 Surrogate light chains Iga (alpha) IgB (Beta)
The ________ mechanisms make genes available or unavailable in chromatin.
Epigenetic
DNA exists in chromosomes tightly bound to _______ and non-_______ proteins, forming chromatin.
Histones
Histone
Chromatin may exist as relatively loosely packed ________ in which genes are available and are transcribed, or as very tightly packed __________ in which genes are maintained in a silenced state.
Euchromatin
Heterochromatin
The structural organization of portions of chromosomes makes some genes available for ________ _______ to initiate the transcription.
Transcription factors
DNA ________ of certain cytosine residues generally silences genes.
Methylation
The modifications of the histone tails of nucleosomes by post-translational ________, ________, or ________ render genes either in the active or inactive state.
Acetylation
Methylation
Ubiquitination
Active remodeling of chromatin by proteins forming the remodeling complexes can either ________ or _______ gene expression.
Enhance
Suppress
These are a class of small noncoding RNAs that control gene expression at the post-transcriptional level by impairing translation or by promoting degradation of the target mRNA. They can also accumulate in the nuclei and regulate gene expression at the transcriptional level.
MicroRNAs (miRNAs)
There are three unlinked gene groups at different chromosomes which encode immunoglobulins. These are…
One for u H-chain (heavy chain)
One for K L-chain (light chain)
One for lambda L chain (light chain)
Individuals codominantly inherit maternal and paternal sets of alleles for L and H chains of Ig molecules. However, ONLY one of the light chain and heavy chain alleles (either maternal or paternal) is expressed in a single B cell. This restriction is called…
Allelic exclusion
In a similar manner, allelic exclusion also governs the expression of ______. The maternal and paternal allotypes are expressed equally since there are many B cells and T cells.
TCR
Stem cell (a precursor of both T and B cells) contains ________ and ______.
Germline Ig
TCR
The variable regions of the chains in T and B cells are determined by rearrangement of the _____.
DNA
T/F. DNA chromosomal rearrangement is the major mechanism of epitope-specific diversity of BCR and TCR.
True
The process of rearrangement includes deletion of DNA/RNA nucleotides and reannealing gene segments. This is all done using _____ and _____ recombination enzymes.
Rag1
Rag2
The _____ and _____ proteins initiate V(D)J recombination by introducing double-strand breaks in the DNA molecules.
Rag1
Rag2
There are two major double-stranded brake repair pathways, which are…
Homologous recombination (HR) Nonhomologous end-joining (NHEJ)
Rag-mediated double-strand breaks are resolved exclusively by (HR/NHEJ).
NHEJ