Lecture 15 (Exam 2) Flashcards
(128 cards)
1
Q
Alternative processing of a primary RNA transcript results in the formation of _______ for the membrane or secreted form of the u heavy chain.
A
mRNA
2
Q
Ag-dependent B cell activation results in an (INCREASING/DECREASING) fraction of the u protein produced as the secreted form.
A
Increasing
3
Q
____, ____, and ____ refer to tail piece, transmembrane, and cytoplasmic segments, respectively.
A
TP
TM
CY
4
Q
____, ____, ____, and ____ are four axons of the Cu gene.
A
Cu1
Cu2
Cu3
Cu4
5
Q
This is the process that leads to increased affinity of Abs for a particular Ag.
A
Affinity maturation
6
Q
Affinity maturation is observed ONLY in Ab responses to ____ Ags.
A
TD
7
Q
T-FH cells and CD40:CD40L interactions are required for _______ _______ of Ig V genes to be initiated.
A
Somatic hypermutation
8
Q
During the Germinal Center (GC) reaction, selection of B cells with high-affinity Ag receptors result in the production of _____ with high affinity for Ag.
A
Abs
9
Q
Abs with an increased affinity (binding) to Ags more efficiently neutralize and eliminate _______.
A
Microbes
10
Q
Affinity maturation occurs within the GC, where somatically mutated BCRs undergo selection on Ag retained on ______.
A
FDCs
11
Q
Ag is retained in the form of ICs and involves the interaction of both complement receptors and _______ with these ICs on FDCs.
A
FcyRIIB
12
Q
Affinity maturation is the process of “fine tuning” of B cell specificity that occurs through a repeated process of somatic hypermutation of ______ and subsequent clonal selection.
A
BCRs
13
Q
Hypermutation can occur anywhere along the ______ region of the Ig genes.
A
VDJ
14
Q
T/F. Both the heavy and light chain Ig genes can be hypermutated, a process of point mutation and repair in the genes encoding the BCR.
A
True
15
Q
In the GCs, B cells express _____, which initiates somatic hypermutation of the Ag-binding site of BCRs. Generally, _____ induces cytosine to uracil deamination.
A
AID
AID
16
Q
AID induces cytosine to uracil ________. This is a mismatch that can be repaired by base excision and mismatch repair mechanism, which recruits error-prone polymerases allowing any base to be incorporated.
A
Deamination
17
Q
In proliferating B cells in the dark zone of GC, Ig V genes undergo point mutations at an extremely (LOW/HIGH) rate.
A
High
18
Q
This rate is estimated to be 1 in 10(3) base pairs per cell division in V gene, which is about 1,000x higher than the spontaneous rate of mutation in other genes. For this reason, mutation in Ig V genes is also called…
A
Somatic hypermutation
19
Q
The V(H) and V(L) genes of expressed heavy and light chains in each B cell contain a total of about _____ nucleotides. This implies that mutations will accumulate in expressed V regions at an average rate of almost one per ______ ______.
A
700
Cell division
20
Q
Ig V gene mutations continue to occur in the progeny of individual B cells. As a result, any B cell clone can accumulate more and more mutations during its life in the _______ _______.
A
Germinal center
21
Q
It is estimated that as a consequence of somatic mutations, the nucleotide sequences of IgG Abs derived from one clone of B cells can have as much as _____ percent gremlin sequence mutated. This usually translates to up to _____ aa substitutions.
A
5
10
22
Q
The mutations are clustered in the V regions, mostly in the Ag-binding complementarity-determining regions. There are far more mutations in _____ than in _____ Abs.
A
IgG
IgM
23
Q
Mutations correlate with increasing ________ of the Abs for the Ag that induced the response.
A
Affinities
24
Q
Somatic mutation of V genes generates Abs with different affinities for _____.
A
Ag
25
Binding of the B cells to Ag displayed on _______ is necessary to rescue the B cells from apoptosis.
Follicular DCs (FDCs)
26
The B cells with the highest affinity for Ag thus have a selective advantage for survival as the amount of available Ag decreases during an immune response. This leads to an average (INCREASE/DECREASE) in the affinity of Abs for Ag as the humoral immune response progresses.
Increase
27
B cells may also present Ag to germinal center _____ cells, which promote B cell survival in a CD40-dependent manner.
T-FH (Follicular T helper)
28
The GC is B cells graveyard. In time, ____ is eliminated and less is available in the GC.
Ag
29
To be rescued from ________, B cells need to express Ag receptors with higher and higher affinity for the Ag. This selection process results in affinity maturation of the Ab response.
Apoptosis
30
B cells that are selected to survive in the _____ produce Ig with increased affinity for the Ag.
GC
31
T/F. Because somatic mutation also generates many B cells that do not express high-affinity receptors for Ag and cannot therefore be selected to survive, the germinal centers are sites of tremendous apoptosis.
True
32
B cells that have undergone somatic mutation migrate into the FDC-rich _______ zone of the germinal center.
Light
33
B cells with high-affinity receptors for the Ag are best able to bind the Ag when it is present at (LOW/HIGH) concentrations by follicular DCs, and these B cells survive preferentially because of several mechanisms.
Low
34
B cell Ag recognition by itself induces expression of anti-apoptotic proteins of the ______ family.
Bcl-2
35
High affinity B cells will preferentially endocytose and present the Ag for _____ cells in the GC with signal via ______ to promote the survival of the B cells.
T-FH
| CD40L
36
Expression of endogenous inhibitors of _____ in high-affinity B cells may be activated when their BCRs recognize Ag and thus be protected from death, while low-affinity B cells are killed.
Fas
37
Many tumors of B cells, B cell _________, develop from B cells in germinal centers. It is caused by chromosomal translocations of various _______ into Ig gene loci.
Lymphomas
| Oncogenes
38
In B cell lymphoma, the DNA breaks associated with somatic hypermutation and isotype switching facilitate incorporation of ________.
Oncogenes
39
Germinal centers may also contribute to the pathogenesis of _________.
Autoimmunity
40
Somatic mutation may produce a _________ B cell clone in the GC.
Self-reactive
41
In TD responses, some of the progeny of activated IgM- and IgD-expressing B cells undergo (HEAVY/LIGHT) chain isotype (class) switching and produce Abs with (HEAVY/LIGHT) chains of different classes, such as gamma, alpha, and epsilon.
Heavy
| Heavy
42
Isotype switching primarily occurs in the germinal centers and is driven by ______ cells.
T-FH
43
Some isotype switching may occur in B cells in extrafollicular foci, driven by extrafollicular _____ cells.
Th
44
Class-switching occurs in response to changing the _______ regions of the _______ chains.
Constant
| Heavy
45
Abs specificity which is determined by the _______ regions in the class-switched Abs remains unaltered.
Variable
46
The capacity of B cells to produce different ____ isotypes provides a remarkable plasticity in humoral immune responses.
Ab
47
Abs of various classes perform distinct effector functions and are involved in defense against different types of ________.
Pathogens
48
B cells activated by T-FH cell signals (______, cytokines) undergo switching to different Ig isotypes.
CD40L
49
Each class of Abs mediates distinct ________ functions.
Effector
50
Isotype switching in response to different types of microbes is regulated by cytokines produced by the ______ cells that are activated by these microbes.
T-FH
51
Intracellular pathogens activate helper T cells of the ______ subset, which produce the cytokine IFN-y and also likely induce IFN-y+T-FH cells to make increased amounts of IFN-y.
Th1
52
IFN-y (Th1) induces ______ switching and IL-4 (Th2) induces ______ switching.
IgG
| IgE
53
The response to intracellular pathogens involves _____ Abs, which block entry of the microbes into host cells, activate complement and promote phagocytosis by macrophages.
IgG
54
________ likely influence T-FH cells differentiation in to IL-4+T-FH cells which produce Th2-type cytokines during the germinal center reaction.
Helminths
55
The response to helminths is mainly driven by ______, which participate in eosinophil- and mast cell-mediated elimination of the helminths.
IgE
56
B cells in different anatomic sites switch to different ______ ______. It is controlled by the local cytokines produced at these sites.
Ab isotypes
57
B cells in mucosal tissues switch to _____, which is the Ab class that is most efficiently transported through epithelia into mucosal secretions, where it defends against microbes by preventing their interaction with epithelial cells.
IgA
58
______ produced by many cell types, including Treg cells and macrophages stimulates switch to, and production of, IgA.
TGF-B
59
______, a cytokines of the TNF family produced by DCs and macrophages, also co-stimulates switching to IgA.
BAFF (B cell activating factor)
60
_______ signals work together with cytokines to induce isotype switching.
CD40 (on B cell)
61
Both isotype switching and affinity maturation are critically dependent on _______.
AID (Activation-Induced Deaminase)
62
______ engagement induces AID.
CD40
63
In immunodeficiencies related to the CD40-CD40L axis, the Ab response to protein Ag is dominated by _____ Abs, whereas there is limited switching to other isotypes.
IgM
64
The mature B cells first produce _____ immunoglobulins. The rearranged VDJ sequences are positioned directly adjacent to other C genes. Every C gene is preceded by a switching (S) sequence that controls the rearrangement process.
IgM
65
AID is a key enzyme required for isotype switching and affinity maturation. AID expression is activated mainly by ______ signals from T-FH cells.
CD40
***CD40L is on the T-FH -- it is the one sending a signal.
66
AID dominates cytosines in single-stranded DNA templates, converting cytidine (C) residues to ______ residues.
Uracil (U)
67
Uracil-N-Glycosylase (UNG) removes U residues to generate abasic sites where the apurinic/apyrimidinic endonuclease ______ creates nicks that lead to a double-stranded break.
APE1
68
Class-switch recombination (CSR) takes place in activated B cells, and it changes the C(u) gene to one of the other _____ genes.
C(H)
69
CSR is preceded by the expression of germline transcripts initiated from intronic promoters. The germline transcription opens the chromatin structure of a specific S region and makes it accessible to the putative _________.
Recombinase
70
CSR takes place between two _______ regions comprising repetitive sequences of palindrome-rich motifs and results in a looped-out deletion of the intervening DNA segments.
Switch (S)
71
CSR is regulated specifically by various ________.
Cytokines
72
CSR is a "switch" of the immunoglobulin isotype from IgM/IgD to ______, ______, or _____, with similar Ag specificity but with different biological properties.
IgG
IgA
IgE
73
_______ cells are morphologically distinct and terminally differentiated B cells committed to abundant Ab production.
Plasma
74
Plasma cells are generated after the activation of B cells through signals from the ______, _____, and _____, and other receptors including cytokine receptors.
BCR
CD40
TLRs
75
(SHORT/LONG)-lived plasma cells are generated in extra follicular compartments during T-indepednent responses and may well be generated early during T-dependent responses in extra follicular B cell foci.
Short
76
(SHORT/LONG)-lived plasma cells are generally found secondary lymphoid organs and in peripheral non-lymphoid tissues.
Short
77
(SHORT/LONG)-lived plasma cells are generated in T-depednetn responses to protein Ag in the germinal center.
Long
78
Long-lived plasma cells are generated by signals from the ______ and ______ via a stage of their precursors called plasmablasts.
BCR
| IL-21
79
These are generated in GC then enter the circulation and home to the bone marrow where they differentiate into long-lived plasma cells.
Plasmablasts
80
Typically 2-3 weeks after immunization with a T-cell dependent Ag, the bone marrow becomes a major site of _____ production.
Ab
81
These plasma cells are maintained by ______ allowing the cells to survive for long periods, often as long as the life span of the host.
BAFF
82
Plasma cells may continue to secrete Abs for months or even years after the _____ is no longer present. These Abs can provide immediate protection if the Ag is encountered later.
Ag
83
It is estimated that almost 50 percent Ab in the blood of a healthy adult is produced by (SHORT/LONG)-lived plasma cells and is specific for Ags that were encountered in the past.
Long
84
This is the development of an individual organism or anatomical or behavioral feature from the earliest stage to maturity.
Ontogenesis
85
B cells that are generated in the bone marrow exit as pre-B cells which are immature and express _____. These cells further mature into naive B cells and then into either ________ B cells or _______ B cells in the spleen.
IgM
Marginal-zone
Follicular
86
When activated, these marginal-zone and follicular B cells can differentiate into _________ and ________ plasma cells, both of which can secrete Abs.
Plasmablasts (Long-lived plasma cell precursors)
| Short-lived
87
With the help of _______ cells, follicular B cells can also differentiate into ________ B cells, which are long-lived, and express Abs of switched class and high affinity for Ag.
T helper
| Memory
88
When reactivated by Ag, memory B cells can differentiate into competent (SHORT/LONG)-lived plasma cells.
Long
89
Most of the plasma cells migrate either to inflamed tissue or to the...
Bone marrow
90
Resolution of inflamed tissue after a successful immune response eliminates the resident _______ cells in the peripheral tissues.
Plasma
91
In the bone marrow, and to a lesser degree in secondary lymphoid organs, (SHORT/LONG)-lived plasma cells survive and provide humoral memory.
Long
92
Memory B cells are generated mainly in the GCs for T-(INDEPENDENT/DEPENDENT) protein Ags.
T-dependent
93
Memory B cells acquire the ability to survive for long periods without continuing _____ stimulation.
Ag
94
Memory B cells express high levels of the anti-apoptotic protein ______.
Bcl-2
95
Memory cells typically express high-affinity (mutated) BCRs and Ig molecules of switched isotypes (other than ____ and/or ____).
IgM
| IgD
96
Abs production is greatly accelerated after secondary exposure to Ags, and this can be attributed to the activation of ________ cells in GCs.
Memory
97
Some memory B cells may remain in the lymphoid organ where they were generated, whereas others exit germinal centers and recirculate between the _______ and lymphoid organs.
Blood
98
Many non-protein Ags, such as polysaccharides and lipids, stimulate Ab production in the absence of _____ cells, and these Ags and the responses they elicit are termed thymus independent or T-independent (TI).
Th
99
The Abs that are produced in the absence of Th cells are generally of low affinity and consist mainly of _____, with limited isotype switching to some IgG subtypes and also to IgA.
IgM
100
TD Ags (proteins) and TI Ags (non-protein Ags) induce distinct Ab responses with different characteristics. The differences largely reflect the influence of _____ cells in the responses to protein Ags.
Th
101
The majority of TI Ags are multivalent, being composed of repeated identical Ag epitopes. Such multivalent Ags may induce maximal cross-linking of the ______ complex on specific B cells, leading to activation without a requirement for cognate T cell help.
BCR
102
T/F. TI Ab responses may be initiated in the spleen, bone marrow, peritoneal cavity, and mucosal sites.
True
103
The marginal zone (MZ) and B-1 cells are especially important for Ab responses to _____ Ags.
TI
104
MZ B cells are a distinct population of B cells in the spleen that mainly respond to _________.
Polysaccharides
105
MZ B cells, after being activated, differentiate into ______-lived plasma cells that produce mainly _____.
Short
| IgM
106
TI Ags may persist for prolonged periods on the surfaces of MZ macrophages in the spleen where they can also be recognized by specific _____ cells.
B-2
107
_____ cells represent another lineage of B cells that respond readily to TI Ags in a similar manner mainly in the peritoneum and in mucosal sites.
B-1
108
The most important TI Ags are...
Polysaccharides
Glycolipids
Nucleic acids
109
TI Ags cannot be processed and presented in association with _____ molecules, and therefore they cannot be recognized by CD4+ T helper cells.
MHC
110
Many polysaccharides activate the complement system by the _________ pathway, generating C3b which first binds to the Ag and then processed into C3d recognized by CR2 on B cell.
Alternative
111
TI responses may also be facilitated by additional signals derived from microbial products that activate ______ on B cells.
TLRs
112
B cell activation is facilitated by the _____/_____ co-receptor on B cells.
CR2/CD21
113
Simultaneous ______ recognition and TLRs signaling may contribute to B cell activation.
PAMPs
114
Activation of B cells through the BCR may be enhanced by complement-coated Ags that can ligate both the BCR and ______.
CR2
115
Some TI Ags can induce Ig isotype switching (other than IgM). In humans, the dominant Ab class induced by pneumococcal capsular polysaccharide is ______.
IgG2
116
________ produced by non-T cells may stimulate isotype switching in TI responses.
Cytokines
117
_____ that help mediate the IgA switch are secreted by many non-lymphoid cells at mucosal sites.
TGF-B
118
_____ produced by DCs and macrophages can induce the synthesis of AID in Ag-activated B cells. This may be further facilitated by the activation of _____ on these B cells.
BAFF
| TLRs
119
Many TI Ags are bacterial polysaccharides of encapsulated _______.
Bacteria
120
TI Ags also contribute to the generation of ________ antibodies, which are present in the circulation of normal individuals and are apparently produced without overt exposure to pathogens.
Natural
121
Most natural Abs are low-affinity anti-carbohydrate Abs, postulated to be produced by peritoneal B-1 cells stimulated by bacteria that colonize the GI tract and by _____ B cells in the spleen.
MZ
122
Effective ________ against microbes and microbial toxins must induce both affinity maturation and memory B cell formation.
Vaccines
123
Memory occurs only if the vaccines are able to activate _______ cells. This concept has been applied to the design of vaccines for capsular polysaccharides, which is incapable of stimulating _______ cells. In these cases, the polysaccharide is covalently linked to a foreign protein to form the equivalent of a _______-_______ conjugate.
T helper
T helper
Hapten-carrier
124
Such vaccines, which are called ________ vaccines, more readily induce high-affinity Abs and memory cells.
Conjugate
125
Polysaccharides that are present on the surface of capsulated bacteria are composed of many identical repeating units of simple sugars. When purified, the polysaccharides are poorly immunogenic, as they are unable to enter the cavity of ______ molecules and therefore they fail to be presented to T cells.
MHC
126
Many polysaccharide vaccines, such as pneumococcal vaccine, induce quite long-lived protective immunity. Rapid and large secondary responses typical of _______ (but without much isotype switching or affinity maturation) may occur on secondary exposure to these carbohydrate Ags.
Memory
127
Ag-Ab complexes can simultaneously bind to the BCR and the _______ receptor through the Fc portion of the antibody.
FcyRIIB
128
As a consequence of the simultaneous ligation of BCR and FcyRIIB receptors, _________ associated with the cytoplasmic tail of the FcyRIIB inhibit signaling by the BCR complex and block B cell activation.
Phosphatases
