Professional Documents
Culture Documents
92
To mount the most effective antibody response that results in the synthesis of highaffinity antibodies, which of the following must occur? (Select all that apply.)
a.
recognition of thymus-independent (TI) antigens
b.
isotype switching
c.
increased expression of TLR9 by B cells
d.
affinity maturation
e.
decreased expression of CD40 by B cells.
93
a.
b.
c.
d.
e.
94
a.
b.
c.
d.
e.
f.
95
A primary focus of clonal expansion is best described as _____.
a.
the location in the B-cell zone where conjugate pairs of B and T cells undergo cellular
proliferation, isotype switching, and somatic hypermutation
b.
the location in the medullary cords where conjugate pairs of B cells and T cells undergo
cellular proliferation and IgM is secreted
c.
the dark zone of the germinal center where centroblasts divide and pack closely together
d.
the initial wave of B-cell proliferation induced by T-independent antigens.
96
A primary focus forms after a circulating naive B cell forms a conjugate pair with _____
in the _____ of a lymph node.
a.
TH1 cell; B-cell zone
b.
cytotoxic T cell; T-cell zone
c.
follicular dendritic cell; germinal center
d.
TFH; medullary cords
e.
CD40 ligand; T-cell zone.
97
Which of the following do not bind to components found on the surface of an activated B
cell? (Select all that apply.)
a.
MHC class II
b.
T-cell receptor
c.
antigen
d.
CD40
e.
C3d
f.
IL-4
g.
CD4
h.
LFA-1
i.
CD40 ligand.
98
B cells migrating directly from a primary focus to the medullary cords in a lymph node
after activation with a T-dependent antigen differentiate into plasma cells that secrete
predominantly _____.
a.
IgD
b.
IgE
c.
sIgA
d.
IgG
e.
IgM.
99
Lymphoblasts upregulate a transcription factor called _____ when they terminally
differentiate into plasma cells.
a.
NFB
b.
Bcl-xL
c.
B-lymphocyte induced maturation protein 1 (BLIMP-1)
d.
CD40
e.
ICAM-1.
910 The primary focus of B-cell expansion forms in the _____, whereas a secondary focus of
B-cell expansion creates the _____.
a.
T-cell area; medullary cords
b.
medullary cords; T-cell area
c.
T-cell area; B-cell area
d.
medullary cords; germinal center
e.
light zone; dark zone.
911 Proliferating centroblasts use the DNA-modifying enzyme activation-induced cytidine
deaminase for ________. (Select all that apply.)
2
a.
b.
c.
d.
e.
cell proliferation
somatic hypermutation
apoptosis
upregulation of CD40
isotype switching.
912 What is the fate of centrocytes in which somatic hypermutation has resulted in highaffinity receptors for antigen? (Select all that apply.)
a.
They die by apoptosis.
b.
They express Bcl-xL.
c.
They process antigen and present it to TFH cells.
d.
CD40 on the centrocyte engages with CD40 ligand on TFH cells.
e.
They undergo phagocytosis by tingible body macrophages.
913
a.
b.
c.
d.
e.
914
a.
b.
c.
d.
e.
915
Match the cell type found in the lymph node in column A with its description in column
Column A
___a. centroblast
___b. tingible body macrophage
___c. naive B cell
___d. follicular dendritic cells (FDC)
___e. memory B cell
Column B
1. not bone marrow-derived hematopoietic
cells
2. engulf apoptotic centrocytes
3. undergo somatic hypermutation
4. make up the mantle zone
5. differentiate under the influence of an IL-4secreting TFH cell
920 _____ in the switch regions positioned 5 to each heavy-chain C gene is induced by
_____.
a.
Somatic hypermutation; TI antigens
b.
Chromatin remodeling; B-cell co-receptor signaling
c.
Recombination; survival signals received from follicular dendritic cells
d.
Transcription; helper T-cell cytokines
e.
Gene repression; apoptotic signals received from tingible body macrophages.
921
Plasma cells and memory B cells differentiate most immediately from _____.
4
a.
b.
c.
d.
centrocytes
centroblasts
B-1 cells
IgG-secreting B cells.
922 Which of the following statements is true regarding the complement component C4B?
a.
Deficiency of C4B is associated with systemic lupus erythematosus (SLE).
b.
C4B has similar properties to those of C4A.
c.
The thioester bond of C4B is preferentially acted upon by amino groups of
macromolecules.
d.
C4B is encoded in the class II region of the MHC.
e.
The gene for C4B is duplicated or deleted in some individuals.
923
a.
b.
c.
d.
e.
f.
g.
Which of the following is able to bind to C1q? (Select all that apply.)
bacterial adhesins
toxoids
IgM
C-reactive protein
hemagglutinin
lipopolysaccharide
classical C3 convertase.
924
a.
b.
c.
d.
e.
925 C3 convertase of the classical pathway is _____, whereas C3 convertase of the alternative
pathway is _____.
a.
C1a; C3bBb
b.
C4bC2a; C3bBb
c.
C3bCR1; C3bBb
d.
C4bC2a; C3bCR1
e.
C1a; C3bCR1.
926 Which of the following statements are true regarding C4? (Select all that apply.)
a.
There are two forms of C4 encoded by separate genes residing in the class II region of the
MHC.
b.
Evolution of the different forms of C4 probably occurred as a result of gene duplication
and diversification.
c.
Because there are two forms of C4, C4 deficiency is the least common human
immunodeficiency.
d.
More than 30% of the human population lacks either C4A or C4B.
e.
C4A and C4B have identical properties.
5
f.
C4B deficiency is associated with increased susceptibility to systemic lupus
erythematosus.
g.
C4A and C4B are monomorphic.
927 Complexes of IgG bound to soluble multivalent antigens can activate the classical
pathway of complement, resulting in the deposition of _____ on the complex, targeting it for
endocytic uptake by cells bearing _____.
a.
C4b; CR2 and Fc receptors
b.
C3b; CR2 and Toll-like receptors
c.
C5-9; CR1 and Fc receptors
d.
C3b; CR1 and Fc receptors
e.
C2a; CR2 and Toll-like receptors.
928
a.
b.
c.
d.
929
a.
b.
c.
d.
930 Describe the ways in which follicular dendritic cells (FDCs) are similar to subcapsular
sinus macrophages.
931 Naive B cells search for specific antigen displayed by follicular dendritic cells in primary
follicles. Naive T cells, however, search for specific antigen presented by ______.
a.
dendritic cells
b.
subcapsular sinus macrophages
c.
medullary sinus macrophages
d.
centrocytes
e.
tingible body macrophages.
932
a.
b.
c.
d.
e.
933 Some types of B-cell tumor have been treated with rituximab, an anti-CD20 monoclonal
antibody, which exerts its effect through a mechanism known as ______ involving the
participation of NK cells.
a.
degranulation
6
b.
c.
d.
e.
neutralization
opsonization
antibody-dependent cell-mediated cytoxicity
receptor-mediated endocytosis.
934 Explain why expression of CD40 ligand by TFH cells is important in the boundary area of
primary follicles in secondary lymphoid tissue as it relates to the targeted delivery of secreted
cytokines to the B-cell surface.
935 Which of the following is a characteristic of follicular dendritic cells in the primary
follicles of secondary lymphoid tissues? (Select all that apply.)
a.
They are bone marrow derived hematopoietic cells.
b.
They provide a stable depository of intact antigens able to bind to B-cell receptors.
c.
They have a large surface area as a result of forming dendrites.
d.
They internalize immune complexes through CR2 receptor cross-linking.
e.
They produce cytokines that induce B cells to proliferate and become centroblasts.
936 A.
What is the main effector function of IgM antibody?
B.
Why is IgM efficient at (i) preventing blood-borne infections and (ii) fixing complement,
but (iii) less efficient than other antibody classes in inducing phagocytosis of immune
complexes?
937
A.
Explain how the poly-Ig receptor transports dimeric IgA antibodies across cellular
barriers, and specify the type of cell barrier involved.
B.
What are the final locations of the transported material?
938
A.
What are the similarities between the activation of mast cells and NK cells via FcRI and
FcRIII, respectively? Be specific.
B.
What are the differences? Again, be specific.
939 Describe the course of events that results in the swollen lymph nodes characteristic of
many infections. Use the following terms in your answer: B lymphoblasts, centroblasts,
centrocytes, follicular dendritic cells, germinal center, primary focus, primary follicle, somatic
hypermutation, boundary region, and tingible body macrophages.
940
A.
What is meant by the term passive transfer of immunity, and how is it achieved? Give
examples.
B.
Give the isotype of the antibodies involved in (i) placental transfer and (ii) transfer into
breast milk, and explain why these antibodies are important.
C.
Do you think it is possible for a pregnant mother who has an autoimmune disease to
transfer autoreactive antibodies to the developing fetus? Explain your answer.
941 Explain the origin of the secretory component and its significance after the release of
dimeric IgA from the apical face of the gut epithelium.
7
942 How does IgE induce the forcible ejection of parasites and toxic substances from the
respiratory and gastrointestinal tracts?
943 From an immunological viewpoint, why would it be inadvisable for a mother who has
recently given birth to move with her newborn to a foreign country where there are endemic
diseases not prevalent in her homeland?
944
a.
b.
c.
d.
e.
945 C3d and iC3b are breakdown products of _____, which binds to _____ of the B-cell coreceptor.
a.
C3a; CR2
b.
C3b; CR2
c.
C3c; CD81
d.
C3c; CD19
e.
C3b; CD19.
946 When bound to CR1, C3b is cleaved by _____, generating pathogen-associated B-cell coreceptor ligands.
a.
factor I
b.
CR2
c.
C3d
d.
CD19
e.
Lyn.
947 The Ig-associated tyrosine kinase _____ phosphorylates the cytoplasmic tail of CD19,
which mediates signal transduction in activated B cells.
a.
CD81
b.
Blk
c.
Fyn
d.
Lyn
e.
Syk.
948
a.
b.
c.
d.
e.
949
a.
b.
c.
d.
e.
The process that drives an increase in antibody affinity for antigen is known as _____.
apoptosis
affinity maturation
antibody-dependent cell-mediated cytotoxicity
opsonization
clonal expansion.
950
a.
b.
c.
d.
e.
FcRn has which of the following characteristics? (Select all that apply.)
It binds to monomeric IgA in acidified endocytic vesicles.
It transports IgG out of the blood into tissue across the endothelium.
It is similar in structure to an MHC class II molecule.
It protects IgA from degradation by plasma proteases.
Two molecules of FcRn are required to bind to each Fc region.
951 The process involving receptor-mediated transport of macromolecules from one side of a
cell to the other is called
a.
phagocytosis
b.
exocytosis
c.
transcytosis
d.
signal transduction
e.
opsonization.
952
a.
b.
c.
d.
e.
Which of the following are correctly matched? (Select all that apply.)
protein F; fibronectin
neutralization; IgE
breast milk; IgG
influenza; hemagglutinin
mucosal epithelium; IgA.
955
a.
b.
c.
d.
e.
breakdown products
anti-inflammatory molecules
adhesins.
956 Denatured toxin molecules called _____ are used to vaccinate individuals to stimulate the
production of _____.
a.
toxoids; neutralizing IgG antibodies
b.
adhesins; neutralizing antibodies
c.
toxoids; passive immunity
d.
adhesins; complement proteins
e.
toxoids; C-reactive protein.
957 Which of the following are characteristics of systemic lupus erythematosus? (Select all
that apply.)
a.
It is an autoimmune disease.
b.
It is associated with a deficiency of C4A.
c.
Increased levels of immune complexes are detected in the blood.
d.
CR1 receptor levels are decreased.
e.
Immune complexes are deposited on the kidney glomeruli, which can lead to kidney
complications.
958 The disadvantage of having a longer hinge region in IgG3 compared with the other IgG
subclasses is a reduction in its serum half-life because of its susceptibility to _____.
a.
increased proteolysis by serum proteases
b.
clearance by erythrocytes via FcR binding
c.
immune complex formation and deposition in kidney glomeruli
d.
complement fixation and uptake by cells bearing receptor CR1
e.
opsonization by neutrophils.
959 Which of the following antibodies activate the classical pathway of complement? (Select
all that apply.)
a.
IgM
b.
IgG1
c.
IgD
d.
IgG3
e.
IgE.
960
a.
b.
c.
d.
e.
The chain of the FcRI receptor is closely related to the _____, which contains _____.
FcRn; MHC class I-like structure
chain of the T-cell receptor complex; ITAM motifs
chain of the FcRIII receptor; ITIM motifs
chain of the FcRI receptor; ITIM motifs
chain of the FcRI receptor; ITIM motifs.
961 Of the Fc receptors for IgG, which one is similar to FcRI in its ability to bind antibody
in the absence of antigen but does not transduce an activating signal until antigen cross-linking
occurs?
10
a.
b.
c.
d.
e.
FcRI
FcRIIA
FcRIIB2
FcRIIB1
FcRIII.
ANSWERS
91
92
b, d
11
93
94
95
96
97
a, d
98
99
910
911
b, e
912
b, c, d
913
914
12
915
916
917
918
919
920
921
922
923
c, d
924
925
926
b, d
927
d
13
928
929
930 FDCs and subcapsular macrophages use their CR1 and CR2 receptors not for the purpose
of receptor-mediated endocytosis, but rather to bind to antigens tagged with C3d or C3b and to
hold them at the cell surface for extended periods of time. Tethering the antigen in this manner
facilitates screening by naive B cells as they travel through secondary lymphoid tissues.
931
932
933
934 CD40 ligand on TFH cells binds to CD40 on B cells, signaling B cells to activate NFB.
NFB is a transcription factor that upregulates ICAM-1 expression on B cells, which binds to
LFA-1 on the TFH cell. As a result, cognate interactions between the B cell and TFH cell are
strengthened, and a synapse at the point of contact facilitates the reorientation of the T-cell
cytoskeleton and secretory apparatus of the Golgi. This ensures that T-cell cytokines are released
onto a localized area of the B-cell surface.
935
b, c
936
A.
The main effector function of IgM is complement activation; it can also neutralize
pathogens and toxins.
14
B.
(i) IgM is the first antibody to be produced by plasma cells during a primary
antibody response and is secreted as a pentamer that circulates in the blood. Because of the large
size of pentameric IgM, it does not penetrate effectively into infected tissues and is most
effective against pathogens in the bloodstream. (ii) In the classical pathway of complement
activation, at least two Fc regions are needed to bind C1, the first complement component in the
pathway. A single pentameric molecule of IgM can thus initiate complement activation. In
contrast, two IgG antibodies in close proximity to each other are needed to bind C1. (iii)
Phagocytic cells carry both complement receptors and Fc receptors for IgG (FcR) and IgA
(FcR), but there are no Fc receptors for IgM. Thus, immune complexes of IgM and antigen
alone cannot be taken up by macrophages through Fc receptor-mediated endocytosis. An
IgM:antigen:C3b complex can be phagocytosed by a macrophage after binding to complement
receptors, but this is not as efficient as having both complement receptors and Fc receptors
cooperating in inducing phagocytosis.
937
A.
Dimeric IgA is made in mucosa-associated lymphoid tissue (MALT) and is
transported across the barrier of the mucosal epithelium. First, dimeric IgA binds to the poly-Ig
receptor on the basolateral surface of an epithelial cell, followed by uptake through receptormediated endocytosis into an endocytic vesicle. On reaching the opposite face of the cell, the
apical surface, the vesicle fuses with the membrane. Here the poly-Ig receptor is cleaved
proteolytically between the membrane-anchoring and the IgA-binding regions, thus releasing
IgA into the mucous layer on the surface of the epithelium. Dimeric IgA remains attached to a
small piece of the poly-Ig receptor, called the secretory component, which holds the IgA at the
epithelial surface through interactions with molecules in the mucus. The rest of the poly-Ig
receptor is degraded and serves no further purpose.
B.
Dimeric IgA is released into the lumen of the gastrointestinal, urogenital, and
respiratory tracts, onto the surface of the eyes, into the nose and throat, and into breast milk
(which is the route by which newborn babies receive protective maternal IgA).
938
A.
Similarities: (1) Activation of both mast cells and NK cells occurs only when their
Fc receptors are bound to antigen:antibody complexes. (2) When cross-linking occurs, both mast
cells and NK cells release the contents of granules through exocytosis, which involves the fusion
of vesicles containing preformed proteins with the cell membrane.
15
B.
Differences: (1) Mast cells bind IgE, whereas NK cells bind IgG. (2) Exocytosis
of granules from mast cells occurs at random around the cell membrane. Exocytosis of granules
from NK cells is highly polarized, focusing only on the target cell to minimize damage to
neighboring cells. (3) IgE binds to FcRI with high affinity in the absence of antigen; mast cells
become activated when antigen becomes available and binds to the receptor-bound IgE. NK cells
bind IgG with low affinity, and bind IgG effectively only when it is already bound to multivalent
antigen. (4) Activated mast cells release inflammatory mediators (histamine and serotonin) that
affect other cells, for example endothelium, causing increased vascular permeability and
vasodilation. Activated NK cells release apoptosis-inducing compounds (perforin and
granzyme/fragmentin) that kill target cells directly. (5) Antibody-dependent cell-mediated
cytotoxicity (ADCC) carried out by NK cells could be induced in newborn infants by maternal
IgG acquired transplacentally. IgE cannot be transferred across the placenta, and so newborn
babies cannot activate mast cells via maternal IgE.
939 B lymphoblasts that have bound specific antigen and encountered their cognate T cells in
the boundary regions between primary follicles and the T-cell area of a lymph node are activated
and start to proliferate, forming a primary focus. The B cells move from the primary foci into
primary follicles, which are primarily B-cell areas, where they become centroblastslarge,
metabolically active, dividing cells. As centroblasts accumulate and proliferate, the primary
follicle enlarges and changes morphologically into a germinal center. Centroblasts undergo
somatic hypermutation while dividing in the germinal center, producing centrocytes with
mutated surface immunoglobulin. Only cells with mutated surface immunoglobulin that can take
up antigen efficiently through receptor-mediated endocytosis and present it to helper T cells (TFH)
will be selected to differentiate into plasma cells or memory cells. Antigen will be encountered at
the surface of follicular dendritic cells as an immune complex. If B cells do not encounter their
specific antigen, they will undergo apoptosis and then be ingested and cleared by tingible body
macrophages. This process takes around 7 days after an infection begins, and the increase in cell
numbers due to lymphocyte proliferation accounts for the swollen lymph nodes.
940
A.
Passive transfer of immunity refers to the process of transferring preformed
immunity from an immune subject to a nonimmune subject. This can be achieved by transferring
whole serum (antiserum), purified antibody, monoclonal antibody, or intact effector or memory
lymphocytes (adoptive transfer).
B.
(i) IgG antibodies transported transplacentally provide passive protection in the
bloodstream and extracellular spaces of tissues until the baby can begin making its own
antibodies, after which time maternal IgG levels decrease. (ii) IgA is transferred into the infants
16
gastrointestinal tract in breast milk and protects the gastrointestinal epithelia from colonization
and invasion by ingested microorganisms.
C.
It is possible for autoreactive antibodies to be transferred passively to a fetus via
the placenta if the isotype is IgG. Any reaction will persist only for as long as the antibodies are
present.
941 During transcytosis the poly-Ig receptor is cleaved by a protease, leaving a small piece of
the original receptor, called the secretory component, still bound to the J chain via disulfide
bonds. Once dimeric IgA is released at the apical face, the carbohydrate moieties of the secretory
component anchor the antibody to mucins of the mucus, enabling the antibodies to bind
subsequently to microbes in the mucus and inhibit the ability of microbes to bind to and invade
the mucosal epithelium of the gut. Instead, the microbe is expelled from the body via mucosal
secretions in the feces.
942 When IgE binds to antigen, leading to cross-linking of FcRI on mast cells in connective
and mucosal tissues, the mast cells rapidly release chemicals that activate smooth muscle to
contract. Muscle activity leads to vomiting and diarrhea in the gastrointestinal tract, and sneezing
and coughing in the respiratory tract, helping to expel the offending pathogen or toxic material.
943 Newborn infants are afforded passive immunity to the pathogens in their environment
through IgG and dimeric IgA. IgG is transferred transplacentally, and dimeric IgA is acquired
through breast milk. If an endemic infection develops in the newborn infant, the IgG antibodies
in the infants bloodstream may not have the appropriate specificity for the foreign antigens
because the mother would not have encountered these antigens previously in their homeland, and
therefore the newborn infant would not have acquired them passively during fetal development.
Furthermore, without maternal IgG, infants are particularly susceptible to infection for the first
6 months of their life, when their immune systems are unable to produce significant levels of
IgG. In addition, infections that breach mucosal surfaces may be more likely to develop during
this time because dimeric IgA against such a pathogen will not be formed in the breast milk until
about a week after the mother has been exposed to the same pathogen.
944
945
b
17
946
947
948
949
950
b, e
951
952
953
954
a, d, e
955
956
957
a, b, c, e
18
958
959
a, b, d
960
961
962
963
964
a, b, d
965
19