Lecture 10 (Exam 2) Flashcards
(117 cards)
1
Q
The maturation of B and T lymphocytes involves a series of events that occur in the generative ________ organs.
A
Lymphoid
2
Q
The maturation of lymphocytes requires a commitment of ________ cells to the B lymphoid or T lymphoid lineage.
A
Progenitor
3
Q
The maturation of lymphocytes requires the proliferation of progenitors and (MATURE/IMMATURE) lymphocytes (providing a large pool of cells for generation of lymphocytes).
A
Immature
4
Q
The maturation of lymphocytes requires sequential and ordered rearrangement of _____ receptor genes and the expression of BCR and TCR proteins.
A
Ag
5
Q
The maturation of lymphocytes requires _______ events (eliminate potentially dangerous self-reactive cells).
A
Selection
6
Q
The maturation of lymphocytes requires the _________ of B and T cells into functionally and phenotypically distinct subpopulations.
A
Differentiation
7
Q
(MULTIPOTENT/PLURIPOTENT) stem cells give rise to distinct B and T lineages.
A
Pluripotent
8
Q
Hematopoietic stem cells (HSCs) give rise to _______ _______ _______.
A
Common lymphoid progenitors (CLPs)
9
Q
Common lymphoid progenitors (CLPs) give rise to what?
A
B cells
T cells
NK cells
10
Q
The commitment to different lineages is driven by various…
A
Transcription factors
11
Q
Pro-B cells can eventually differentiate into…
A
FO B cells (Follicular)
MZ B cells (Marginal zone)
B-1 cells
12
Q
Pro-T cells may commit to either…
A
aB T cells (alpha/beta)
yd T cells (gamma/delta)
NK cells
13
Q
Proliferation of the committed T and B cell progenitors is stimulated by _______, with _____ being most critical.
A
Cytokines
IL-7
14
Q
Proliferation ensures that a large pool of progenitor cells is available for generation of a high ________ of mature lymphocytes.
A
Diversity
15
Q
If a pre-Ag receptor is successfully rearranged, it provides ________ signals that select the cell.
A
Survival
16
Q
In the thymus, _______ cells produce IL-7 that drives the proliferation of human T cell progenitors.
A
Stromal
17
Q
Also, _____ produced by stromal cells in the bone marrow promotes B cell development at all stages of human life.
A
IL-7
18
Q
The development of NK cells occurs in the thymus and it depends on ______.
A
IL-15
19
Q
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.
A
Ag
20
Q
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.
A
Heavy
21
Q
First in developing a/B T cells, the ______ gene locus opens up and becomes accessible for TCR gene rearrangement and expression.
A
TCR B (Beta)
22
Q
The ______ and ______ transcription factors commit developing lymphocytes to the T cell lineage.
A
Notch-1
GATA-3
23
Q
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.
A
Notch
24
Q
The ______ also induces the expression of genes involved in development of aB T cells.
A
GATA-3
25
Some genes (which encode the components of pre-TCR) undergo _____ recombination.
V(D)J
26
The _____ and _____ proteins regulate the TCR and BCR rearrangement.
Rag-1
| Rag-2
27
These transcription factors induce the expression of genes required for B cell development.
EBF (Early B cell factor)
E2A
Pax-5
28
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)
```
29
The ________ mechanisms make genes available or unavailable in chromatin.
Epigenetic
30
DNA exists in chromosomes tightly bound to _______ and non-_______ proteins, forming chromatin.
Histones
| Histone
31
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
32
The structural organization of portions of chromosomes makes some genes available for ________ _______ to initiate the transcription.
Transcription factors
33
DNA ________ of certain cytosine residues generally silences genes.
Methylation
34
The modifications of the histone tails of nucleosomes by post-translational ________, ________, or ________ render genes either in the active or inactive state.
Acetylation
Methylation
Ubiquitination
35
Active remodeling of chromatin by proteins forming the remodeling complexes can either ________ or _______ gene expression.
Enhance
| Suppress
36
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)
37
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)
38
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
39
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
40
Stem cell (a precursor of both T and B cells) contains ________ and ______.
Germline Ig
| TCR
41
The variable regions of the chains in T and B cells are determined by rearrangement of the _____.
DNA
42
T/F. DNA chromosomal rearrangement is the major mechanism of epitope-specific diversity of BCR and TCR.
True
43
The process of rearrangement includes deletion of DNA/RNA nucleotides and reannealing gene segments. This is all done using _____ and _____ recombination enzymes.
Rag1
| Rag2
44
The _____ and _____ proteins initiate V(D)J recombination by introducing double-strand breaks in the DNA molecules.
Rag1
| Rag2
45
There are two major double-stranded brake repair pathways, which are...
```
Homologous recombination (HR)
Nonhomologous end-joining (NHEJ)
```
46
Rag-mediated double-strand breaks are resolved exclusively by (HR/NHEJ).
NHEJ
47
There are 3 mechanisms of Rag recombination enzymes, which are...
Somatic recombination
mRNA splicing
Junctional diversity
48
Heavy chain has 4 separate gene segments in chromosome 14, which are...
These segments contain multiple copies of each segment.
VDJC
49
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 ______ sequence and thus all B cells are different.
V-D-J
50
Recombination starts with the ______ ______ (B cell) and ______ _____ (T cell). If the resultant product is functional, the rearrangement of the ______ ______ (B cell) or _____ _____ (T cell) occurs.
Heavy chain
Beta-chain
Light chain (kappa or lambda)
Alpha-chain
51
The cellular expression of ______ and ______ is restricted to B and T lymphocytes during their developmental stages. These are responsible for performing recombination of BCR and TCR during the process of VDJ recombination.
Rag1
| Rag2
52
In achieving BCR diversity, first, ____ and ____ are chosen and DNA in between them is deleted.
D
| J
53
In achieving BCR diversity, second, a ____ segment is chosen and DNA between _____ and _____ is deleted.
V
V
DJ
54
In achieving BCR diversity, third, a ____ segment is chosen and DNA between _____ and _____ is deleted.
C
C
VDJ
55
In a B cell, the chance to produce a "productive rearrangement" (without stop codons in the sequence) is about _____ percent. There will be a test (transcription and translation) for selection of "productive rearrangement".
10
56
When "productive rearrangement" is confirmed -- the "competition" between paternal and maternal _____ _____ genes is over and the recombination of other segments is stopped. The mechanism of stopping remains unknown.
Heavy chain
57
If the V-H rearrangement is productive, then the B cell proliferates for a while and takes care of the _____.
V-L
58
The kappa and lambda light chains do not have _____ segments.
D
59
The recombination rules are the same for V-L chain as for ____ chain.
V-H
60
There will be a second test for selection of "productive rearrangement", this time for the V-L sequence. The final result is each B cell produces only ONE kind of ____ and ____.
V-H
| V-L
61
Because the number of combinations possible is very big, B cells produced can recognized any _____ possible.
Ag
62
For light chains, the (KAPPA/LAMBDA) chain is from chromosome 2. The (KAPPA/LAMBDA) chain is from chromosome 22.
Kappa
| Lambda
63
The VDJ rearrangement segment facilitates the synthesis of a u (Mu) or d (delta) heavy chain controlled by alternative ______ ______. This then associates with a light chain, thereby forming an _____ or _____ molecule, which is displayed on the cell-surface of a naive B cell.
mRNA splicing
IgM
IgD
64
Other non-IgM/IgD heavy chains are produced by the ______-______ _______, a process that exchanges the constant region of the heavy chain (CH). This deletional-recombination reaction requires the enzyme _______-_______ _______ _______.
Class-switch recombination
| Activation-Induced Cytidine Deaminase (AID)
65
AID is only expressed in activated ____ cells.
B
66
AID introduces ______ residues into the DNA of S regions, and thus induces the generation of DNA breaks at switch regions (S) followed by the repair of DNA.
Uracil
67
In junctional diversity, ______ adds or removes nucleotides to the exposed ends of the V, (D), or J genes before they are reunited.
TdT (Terminal Deoxynucleotidyl Transferase)
68
The process of V(D)J recombination generates a repertoire of different TCR and BCR molecules for recognition of various microbial antigens. But, the V(D)J recombination alone is not enough to produce a huge variety of TCRs and BCRs which would recognize all antigens possible. The inaccuracies of joining is achieved by _______ _______ mediated by TdT further increases the diversity of TCRs and BCRs.
Junctional diversity
69
Junctional diversity is generated at the points between the joining genes. It results from the loss of nucleotides through the action of exonuclease(s) and from the addition of ____ and ____ nucleotides.
N
| P
70
An asymmetric opening of hairpin loops generates ____ nucleotides.
P
71
It is the self-complementarity of P nucleotides that leads to their ________ appearance and to their name.
Palindromic
72
The opening of the ______ ______ produces short, self-complementary single stranded extensions that can be incorporated into junctions, or can be removed via an exonuclease activity.
Hairpin loops
73
TdT adds _____ nucleotides.
N
74
T/F. 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.
True
75
During lymphocyte development, checkpoint one is after the production of the first polypeptide chain of the two-chain ______ ______ is completed.
Ag receptor
76
During lymphocyte development, checkpoint two follows the completion of production of the second polypeptide chain of the ______ ______.
Ag receptor
77
Checkpoints ensure that only lymphocytes that have successfully completed Ag receptor gene rearrangement processes are selected to mature. The selection eliminates potentially harmful ______-______ lymphocytes.
Self-reactive
78
The pre-Ag and Ag receptors deliver survivor ______ for their proliferation and continued maturation.
Signals
79
The pre-Ag receptors are called ______ in B cells and ______ in T cells.
pre-BCRs
| pre-TCRs
80
The pre-Ag receptors contain only one polypeptide chain present in a mature Ag receptor and a _________ receptor chain.
Surrogate
81
The pre-BCRs contain the Ig _____ _____ chain.
u (Mu) heavy
82
The pre-TCRs contain the ______ ______ chain.
TCR B (beta)
83
The _____ _____ chain gene is the first Ag receptor gene to be completely rearranged in B cells.
Ig heavy
84
Developing B cells that successfully rearrange their Ig heavy chain genes express the _____ heavy chain protein and assemble the ______.
u (Mu)
| pre-BCR
85
Developing T cells that make a productive TCR B chain gene rearrangement synthesize the _____ ____ chain protein and assemble the _______.
```
TCR B (beta)
pre-TCR
```
86
About 30 percent of developing B and T cells make productive _______ rearrangements of Ag receptor gene (capable of generating a protein). If cells make _______ rearrangements, the pre-Ag receptors are not expressed, the cells do not receive survival signals and undergo apoptosis.
In-frame
| Out-of-frame
87
The assembled ______ and ______ provide signals for survival, proliferation and further development of early B and T lineage cells.
pre-BCRs
| pre-TCRs
88
B and T lymphocytes with functional pre-Ag receptors proceed to express genes encoding the _______ ______ of the BCR or TCR. If these cells make productive rearrangements of the _______ _______, they express the complete Ag receptor while they are still immature.
Second chain
| Second chain
89
Lymphocytes which express useful Ag receptors are preserved by a process called ________ ________.
Positive selection
90
Positive selection of T cells ensures the maturation of CD8 or CD4 T cells whose receptors don't recognize _______ but can recognize _______ molecules (class I or class II, respectively).
Self-Ags
| MHC
91
T cells positively selected by self MHC molecules in the thymus are able to recognize foreign Ag displayed by the same self MHC molecules on ______ in peripheral tissues.
APCs
92
Negative selection of immature lymphocytes is an important mechanism for maintaining the _______ _______ to many self Ags.
Central tolerance
93
T/F. Negative selection occurs shortly after Ag receptors are first expressed on B and T cells.
True
94
(POSITIVE/NEGATIVE) selection eliminates harmful T cells and alters harmful B cells whose Ag receptors bind strongly to self Ags present in the thymus or bone marrow.
Negative
95
Developing harmful T cells with a high affinity for self Ags are eliminated by apoptosis, a phenomenon known as _______ _______.
Clonal deletion
96
Developing harmful B cells with a high affinity for self Ags undergo the second attempt in Ig gene rearrangement, a process called ________ _______. If this fails, the self-reactive B cells die, also called clonal deletion.
Receptor editing
97
Most B cells that develop from fetal liver, the derived stem cells differentiate into the (B1/B2) lineage.
B1
98
B lymphocytes that arise from bone marrow precursors after birth give rise to the (B1/B2) lineage.
B2
99
A subset of B lymphocytes, called B1 cells, expresses limited BCR diversity because ______ is not expressed in the fetal liver. There is no junctional diversity.
TdT
100
The large numbers of B1 cells are found as a self-renewing population in the ________ and _______ sites.
Peritoneum
| Mucosal
101
B1 cells spontaneously secrete ______ Abs that often react with microbial polysaccharides and lipids as well as oxidized lipids. These Abs are sometimes called ________ antibodies because they are present in individuals without overt immunization.
IgM
| Natural
102
B1 B cells contribute most of the serum IgM during the early phases of ________.
Infection
103
Following rearrangement of their BCR chain genes and removal of autoreactive cells via central tolerance, immature B2 B cells relocate to the ________.
Spleen
104
The immature B2 B cells differentiate into either _____ B cells or ______ B2 cells.
```
Marginal Zone (MZ)
Mature follicular (FO)
```
105
The affinity of the BCRs for self Ags may contribute to differentiation B2 cells into:
- FO B2 cells are recirculating ________
- MZ B2 cells are abundant in the _______, and can also be found in the LNs.
Lymphocytes
| Spleen
106
MZ B cells localize to the splenic marginal zone and respond to ______-______ Ags.
Blood-borne
107
FO B2 cells require constant replenishment from bone marrow. FO B2 cells respond to protein Ags in a T cell-dependent manner, and progressively undergo immunoglobulin ________ ________ and ________ ________.
Isotype switching
| Affinity maturation
108
Only mature FO B2 cells upon T cell-dependent activation develop into long-lived ________ cells or ________ cells.
Plasma
| Memory B
109
The MZ B cells are predominantly self-renewing. Most responses of MZ B cells are (DEPENDENT/INDEPENDENT) of/on T cell help.
Independent
110
MZ B cells are located primarily in the vicinity of the _______ _______ in the spleen.
Marginal sinus
111
Similar to B1 cells, MZ B2 cells have BCRs of limited diversity which respond to polysaccharide Ags and to generate natural Abs. MZ B2 cells can be found in the spleen as well as in the _______ _______.
Lymph nodes
112
MZ B cells respond very rapidly to blood-borne microbes and differentiate into short-lived IgM-secreting _______ cells.
Plasma
113
Although MZ B cells generally mediate T cell-(DEPENDENT/INDEPENDENT) humoral immune responses to circulating pathogens, marginal zone B cells also appear capable of mediating some T cell-(DEPENDENT/INDEPENDENT) immune responses.
Independent
| Dependent
114
Recombination of TCR y and d (gamma and delta) proceeds in a fashion similar to that of TCR B and a (beta and alpha), although the order of rearrangement appears to be less _______.
Rigid
115
The rearrangement of TCR B, y, or d loci is initiated simultaneously. If a cell first success in productively rearranging its TCR y or TCR d loci before it makes a productive TCR B rearrangement, it is selected in to the _____ T cell lineage.
yd (gamma/delta)
116
About _____ of developing T cells become yd T cells and _____ of developing T cells become aB T cells.
10 percent
| 90 percent
117
The limited diversity of expressed yd TCRs occurs because only a few of the available ____, _____, and ____ segments are used in mature yd T cells for unknown reasons.
V
D
J
