THE IMMUNE SYSTEM, FOURTH EDITION
CHAPTER 14: IgE-MEDIATED IMMUNITY AND
ALLERGY
14–1
a.
b.
c.
d.
e.
Which of the following are matched correctly? (Select all that apply.)
type I hypersensitivity: IgE
type II hypersensitivity: IgG
type III hypersensitivity: immune complexes
type IV hypersensitivity: IgG
type IV hypersensitivity: delayed-type hypersensitivity.
14–2
a.
b.
c.
d.
e.
Which of the following are associated with soluble antigen? (Select all that apply.)
type I hypersensitivity
type II hypersensitivity
type III hypersensitivity
type IV hypersensitivity
mast-cell activation.
14–3 Match the term in column A with its description in column B.
Column A
___ a. delayed-type hypersensitivity
Column B
1. innocuous environmental antigen
___ b. hygiene hypothesis
2. type IV hypersensitivity
___ c. allergy
3. a state of hypersensitivity
___ d. immediate hypersensitivity
4. type I hypersensitivity
___ e. allergen
5. epidemic of allergy
14–4
a.
b.
c.
d.
Which of the following is not mediated by antibodies?
type I hypersensitivity
type II hypersensitivity
type III hypersensitivity
type IV hypersensitivity.
14–5
a.
b.
c.
d.
Which of the following is associated with type III hypersensitivity?
nickel
recombinant human insulin
plant oil
mouse-derived monoclonal antibody
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e.
helminth infection.
14–6 _____ hypersensitivity reactions interact with soluble epitopes and not cell-surface
associated epitopes.
a.
type I and II
b.
type I and III
c.
type I and IV
d.
type II and III
e.
type II and IV
f.
type III and IV.
14–7 Identify four different ways in which an individual may come into contact with an
allergen and provide two examples of allergens for each type of contact.
14–8 A.
Describe in detail the mechanism responsible for mast-cell activation during a
type I hypersensitivity reaction.
B.
What are the products of mast-cell activation?
14–9 Adaptive immune responses targeted at infections by helminth worms and other parasitic
multicellular animals employ all of the following except _____. (Select all that apply.)
a.
CD8 T cells
b.
IgE
c.
eosinophils
d.
mast cells
e.
CD4 TH2 cells
f.
basophils
g.
neutrophils
h.
IL-4.
14–10 During a primary immune response IgM sometimes switches to IgE. Which of the
following best describes the consequence of this early switch?
a.
The B cell would switch again to IgG3.
b.
The B cell would remain in the germinal center but would not differentiate into a plasma
cell.
c.
The B cell would die by apoptosis.
d.
The IgE produced would have low affinity for antigen.
14–11
a.
b.
c.
d.
e.
Which of the following regarding FcεRI is false?
It is expressed on the surface of mast cells and basophils.
It is a low-affinity receptor involved in type I hypersensitivity reactions.
It binds to IgE in the absence of antigen.
It is a membrane-bound tetramer.
It contains signaling components that re activated following antigen cross-linking.
14–12
A.
Explain why it is essential that FcεRI and Fcε RII are not able to bind simultaneously to
2
the same IgE molecule.
B.
Why does simultaneous binding not occur?
14–13 The sheddase _____ cleaves FcεRII on the cell surface, resulting in the production of
monomeric and trimeric forms of FcεRII.
a.
cathepsin G
b.
CR2
c.
eotaxin
d.
major basic protein
e.
ADAM10.
14–14 All of the following are released immediately by mast cells after FcεRI cross-linking
except _____.
a.
heparin
b.
eicosanoids
c.
neutral proteases
d.
histamine
e.
TNF-α.
14–15 Lipid mediators produced by activated mast cells include which of the following? (Select
all that apply.)
a.
platelet-activating factor
b.
cathepsin G
c.
chymase
d.
leukotrienes
e.
carboxypeptidase
f.
prostaglandins.
14–16 All of the following are biological effects mediated by the products of mast cells except
_____.
a.
chemotaxis of neutrophils, eosinophils, and effector T cells
b.
growth factor secretion
c.
smooth muscle contraction
d.
connective tissue remodeling
e.
All of the above are mediated by mast cells.
14–17
a.
b.
c.
d.
e.
Identify the mismatched pair.
TNF-α: immediate release from mast cells
mucosal mast cell production: T-cell immunodeficiencies
connective tissue mast cells: chymotryptase
lipid mediator: prostaglandins
leukotrienes: increase vascular permeability.
14–18 Prostaglandin D2 (PGD2) enhances all of the following except _____.
a.
smooth muscle contraction
b.
chemotaxis of neutrophils
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c.
d.
increased vascular permeability
vasodilation.
14–19 Which of the following directly inhibits the cyclooxygenase pathway by inhibiting the
activity of prostaglandin synthase?
a.
ADAM10
b.
experimental anti-IgE
c.
aspirin (acetyl salicylate)
d.
chymotryptase
e.
ADAM33.
14–20
a.
b.
c.
d.
e.
_____ released by TH2 cells promotes an elevated level of eosinophils in the circulation.
IL-4
IL-13
TNF-α
FcγRII
IL-5.
14–21
A.
Explain the importance of allergens having protease activity in the context of antigenspecific T-cell activation.
B.
Provide a specific example of a major allergen that has protease activity.
14–22 Match the physical effects of IgE-mediated mast-cell degranulation in column A with the
tissue exposed to the allergen in column B.
Column A
Column B
___ a. decrease in blood pressure
1. respiratory tract
___ b. diarrhea
2. heart and vascular system
___ c. swelling of tissues
3. gastrointestinal tract
___ d. constriction of the throat
___ e. wheezing
___ f. vomiting
___ g. violent bursts of sneezing
14–23 Explain briefly how penicillin initiates a type I hypersensitivity response.
14–24
A.
Explain how erythrocytes become coated with complement component C3b during an
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allergic reaction to penicillin.
B.
Why is this important to the mechanism by which IgE antibodies are produced?
14–25 Why are antihistamines used to treat allergic rhinitis and allergic asthma? What
symptoms of each disease, respectively, do they alleviate.
14–26
A.
Describe two ways in which the immunoglobulins acting as antigen receptors on the
surface of a mast cell differ from the immunoglobulins acting as the antigen receptors on the
surface of a B cell.
B.
What is the essential difference in response of these two cell types when antigen binds to
these surface immunoglobulins.
12–27 Some allergies can be treated by a procedure called desensitization.
A.
Explain two current approaches to desensitization.
B.
Explain the main disadvantage associated with each.
14–28 Give three ways in which a susceptible person can help to minimize the risk of having an
allergic reaction.
14–29 How do mast cells contribute to innate immunity?
14–30 What are the effects of histamine binding to the H1 receptor on smooth muscle, mucosal
epithelia, and the endothelial cells of blood vessels.
14–31
a.
b.
c.
d.
e.
The antigens that provoke hypersensitivity reactions are referred to as
T-independent antigens
superantigens
subunit vaccines
attenuated vaccines
allergens.
14–32
a.
b.
c.
d.
e.
Which of the following allergens is not likely to be encountered through inhalation?
plant pollen
metals
animal dander
mold spores
house dust mite feces.
14–33 _____ express FcεRI and contain granules containing inflammatory mediators. (Select all
that apply.)
a.
macrophages
b.
activated eosinophils
c.
mast cells
d.
natural killer cells
e.
basophils.
5
14–34 Match the mast cell product in column A with its biological effect in column B.
Column A
Column B
___ a. IL-4
1. activates endothelium
___ b. CCL3
2. amplifies TH2-cell response
___ c. TNF-α
3. increases vascular permeability
___ d. histamine
4. connective tissue matrix remodeling
___ e. tryptase
5. chemotaxis
14–35 Aspirin (acetyl salicylate) inhibits prostaglandin synthesis by binding irreversibly to
prostaglandin synthase, the first enzyme in the _____ pathway.
a.
cyclooxygenase
b.
carboxypeptidase
c.
metalloprotease
d.
lipooxygenase
e.
peroxidase.
14–36
a.
b.
c.
d.
e.
Which of the following is associated with eosinophilia? (Select all that apply.)
IL-5-induced proliferation
endocardium damage
neuropathy
B-cell lymphoma
decreased bone marrow function.
14–37 Which of the following genetic polymorphisms is associated with a predisposition to
asthma? (Select all that apply.)
a.
promoter variants of IL-5
b.
structural variant of IgG receptor
c.
HLA class II allotypes
d.
β2-adrenergic receptor variant
e.
ACOX5 (5-lipoxygenase).
14–38
a.
b.
c.
d.
e.
The wheal-and-flare inflammatory reaction is an example of
an immediate type I allergic response
a late-phase type I allergic response
a late-phase type IV allergic response
an immediate type III allergic response
a late-phase type III allergic response.
14–39 Which of the following tests is used to determine whether a particular allergen is
responsible for asthma?
a.
measure wheal-and-flare diameter after intradermal injection of allergen
b.
measure Arthus reaction diameter after intradermal injection of allergen
c.
inject a controlled amount of allergen intradermally and observe urticaria
d.
measure peak expiratory flow rate (PEFR) following inhalation of allergen
e.
measure eosinophils in nasal secretions following inhalation of allergen.
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14–40
a.
b.
c.
d.
e.
Which of the following are consequences of anaphylactic shock? (Select all that apply.)
smooth muscle contraction
immune complex deposition on blood vessels
loss of blood pressure
constriction of airways
complement activation.
14–41 During the course of a successful desensitization process, the patient’s antibodies will
change from an _____isotype to an _____ isotype.
a.
IgG4:IgE
b.
IgE:IgM
c.
IgA:IgM
d.
IgG1:IgG4
e.
IgE:IgG4.
14–42 Which of the following are potential means by which type I allergic reactions can be
managed or treated? (Select all that apply.)
a.
Use antihistamines to block histamine binding to H1 histamine receptors.
b.
Use corticosteroids to suppress inflammation.
c.
Desensitize the patient by feeding them allergen and skewing the immune response from
an IgE to an IgA response.
d.
Anergize allergen-specific T cells through vaccination with allergen-derived peptides.
e.
Administer Il-4, IL-5, or IL-1β to promote TH1 responses.
f.
Block high-affinity IgE receptors to prevent mast-cell degranulation.
14–43 Anita Garcia, 17 years old, and her roommate Rosa Rosario were celebrating a friend’s
birthday at a dessert buffet at a local restaurant when Anita developed acute dyspnea, and
angioedema. She complained of an itchy rash, and then had difficulty swallowing. Rosa drove
Anita to the emergency room two blocks away rather than wait for an ambulance. As they
approached the hospital, Anita lost consciousness. This medical emergency would most probably
result in immediate _____ before any subsequent treatment.
a.
subcutaneous injection of epinephrine
b.
intravenous injection of corticosteroids
c.
intravenous injection of antihistamine
d.
intravenous injection of antibiotics
e.
intravenous injection of a nonsteroidal anti-inflammatory drug.
14–44 Look again at Question 14–43. What do you think Anita was suffering from? Given the
circumstances in which the episode occurred, suggest a likely cause.
ANSWERS
7
14–1 a, b, c, e
14–2 a, c, d, e
14–3 a—2; b—5; c—3; d—4; e—1
14–4 d
14–5 d
14–6 b
14–7 (i) Inhalation: house dust mite feces, animal dander. (ii) Injection: drugs administered
intravenously, wasp venom. (iii) Ingestion: peanuts, drugs administered orally. (iv) Contact with
skin: poison ivy, nickel in jewelry.
14–8
A.
If an individual becomes sensitized to antigen by making antibodies of the IgE isotype
during first exposure, then a type I hypersensitivity reaction may result if antigen is encountered
again. The IgE made initially binds stably via its Fc region to very high-affinity FcεRI receptors
on mast-cell surfaces. When antigen binds to this IgE, cross-linking of FcεRI occurs, delivering
an intracellular signal that activates the mast cell.
B.
Mast cells contain preformed granules containing a wide range of inflammatory
mediators that are triggered to be released extracellularly through an exocytic mechanism called
degranulation. The inflammatory mediators contained in the granules and released immediately
include histamine, heparin, TNF-α, and proteases involved in the remodeling of connective tissue
matrix. The proteases include tryptase and chymotryptase (expressed by mucosal and connective
mast cells, respectively), cathepsin G, and carboxypeptidase. Additional inflammatory mediators
are generated after mast-cell activation, including IL-3, IL-4, IL-5, IL-13, GM-CSF, CCL3,
leukotrienes C4 and D4, and platelet-activating factor.
14–9 a, g
14–10 d
14–11 b
14–12
A.
Armed mast cells and basophils become activated when IgE molecules bound to FcεRI
on their cell surface become cross-linked. Normally this occurs when antigen is bound to IgE. If
IgE were able to bind to FcεRI using one domain, and at the same time bind to FcεRII using a
different domain, then IgE itself would mediate cross-linking of FcεRI and cause cellular
activation in the absence of antigen.
B.
This does not occur because IgE has two distinct binding sites for FcεRI and FcεRII, and
when one or the other of these binding sites is occupied, the conformation of IgE is altered so
that it is unable to bind to the other receptor.
8
14–13 e
14–14 b
14–15 a, d, f
14–16 e
14–17 b
14–18 a
14–19 c
14–20 e
14–21
A.
Particles containing proteins that stimulate allergic responses will be more easily broken
down by proteolysis, enabling more effective release of the allergen. Proteolytic degradation
results in the formation of peptides that will bind to MHC class II molecules and consequently
stimulate TH2 cells.
B.
Present in the feces of the house dust mite Dermatophagoides pteronyssimus is a cysteine
protease that is an allergen responsible for 20% of human allergies in North America.
14–22 a—2; b—3; c—2; d—1; e—1; f—3; g—1
14–23 The reactive bond in the β-lactam ring of penicillin reacts with proteins on the surface of
human cells, with erythrocytes most commonly being involved. This modification generates a
foreign epitope to which TH2 cells and B cells respond.
14–24
A.
C3b becomes deposited on the cell surface of penicillin-modified erythrocytes because a
bacterial infection is ongoing (the reason that penicillin was administered in the first place). The
erythrocyte becomes coated as a bystander effect of complement activation.
B.
C3b on the penicillin-modified erythrocyte binds to CR1 on macrophages in the spleen,
which facilitates receptor-mediated endocytosis and the subsequent processing and presentation
of the penicillin–protein conjugate peptide. Then TH2 cells interact with the peptide:MHC class
II complexes, become activated, and provide help to B cells with IgE B-cell receptors specific
for the penicillin–protein conjugate.
14–25 Mast cells activated by inhaled allergens in the type I hypersensitivity reaction that
causes allergic rhinitis or asthma release histamine. Histamine binding to its receptors on smooth
muscle causes the bronchial constriction typical of asthma and the difficulty in breathing.
Histamine binding to receptors on vascular endothelium causes increased permeability of the
9
epithelium and inflammation of nearby tissue, causing the runny nose and swollen eyes typical
of allergic rhinitis, and also an accumulation of mucus and fluid in the bronchi typical of allergic
asthma. By blocking histamine action, antihistamines help alleviate these symptoms.
14–26
A.
(i) The immunoglobulin on a mast cell is an IgE antibody that has become bound to the
mast cell’s FcεRI receptor, whereas the immunoglobulin on a B cell is a transmembrane form
made by the cell itself. (ii) A B cell might have any class of immunoglobulin on its surface,
whereas mast cells have only IgE. (iii) IgE molecules of many different antigen specificities can
be bound to the surface of an individual mast cell, whereas an individual B cell carries
immunoglobulin molecules of only one specificity.
B.
After binding to antigen, mast cells become operational as effector cells without the need
to undergo proliferation or differentiation. In contrast, after antigen binds to a surface
immunoglobulin on a B cell, the cell must proliferate and differentiate to produce effector cells
(antibody-secreting plasma cells).
14–27
A.
(i) One approach to desensitization is the subcutaneous injection of the allergen itself into
sensitized individuals with the aim of skewing the immune response from an IgE to an IgG4
isotype. This is achieved by gradually increasing the subcutaneous allergen concentration over
time, which favors IgG over IgE production. When antigen is encountered subsequently, IgG
will compete with IgE for binding and inhibit IgE cross-linking on mast-cell surfaces. (ii) The
second approach involves vaccination with allergen-derived peptides designed to be bound by
HLA class II molecules and presented to allergen-specific TH2 cells with the aim of inducing
anergy in these T cells. This would prevent them from giving help to allergen-specific naive B
cells, thus preventing the production of more IgE antibody on repeated exposures to the
environmental allergen.
B.
(i) A risk of the first approach is the possibility of activating a systemic anaphylactic
response after mast-cell activation. Because the patient was previously sensitized, IgE antibodies
against allergen are present and, if bound to mast cells, will induce mast-cell degranulation. In
the event of an anaphylactic response to an allergy shot, the patient will have epinephrine
administered immediately by the attending physician or nurse practitioner. (ii) With the peptide
vaccination approach, allergen-specific T cells are rendered anergic and there is no risk of
triggering an anaphylactic reaction. However, the disadvantage of this approach is that because
the HLA class II genes are highly polymorphic, the vaccine would have to include sufficient
peptides able to bind to most HLA class II allotypes, or it would need to be custom made for
each individual on the basis of their HLA class II type.
14–28 (i) Avoid contact with allergens as much as possible by modifying their behavior and
their home environment. (ii) Use pharmacological agents that inhibit allergic responses. (iii)
Undergo desensitization therapy to divert immune responses from IgE to IgG4 isotype.
14–29 Mast cells express Toll-like receptors, which can bind to pathogen-associated molecules
and stimulate the production of cytokines and chemokines that participate in innate immune
responses.
10
14–30 When smooth muscle cells bind histamine using H1 receptors, they contract. In
combination with increased mucus production by mucosal epithelium this produces a variety of
effects, for example, wheezing due to bronchial constriction, coughing, sneezing, watery eyes,
nasal discharge, itchiness, and, if the reaction occurs in the gut, vomiting and diarrhea. When
endothelial cells of blood vessels bind histamine, an increase in vascular permeability enables the
entry of fluid (edema) and leukocytes into affected tissues.
14–31 e
14–32 b
14–33 b, c, e
14–34 a 2; b 5; c 1; d 3; e 4
14–35 a
14–36 a, b, c
14–37 c, d, e
14–38 a
14–39 d
14–40 a, c, d
14–41 e
14–42 a, b, d, f
14–43 Rationale: The correct answer is a. This is a case of anaphylactic shock caused by a food
allergy. Anita’s sudden onset of shortness of breath, swelling of mucosal tissues causing
difficulty in breathing, and rash are characteristic of a type I hypersensitivity reaction after the
rapid absorption of allergen into the bloodstream and systemic activation of mast cells in the
connective tissue of blood vessels. Given the life-threatening nature of this medical emergency,
where asphyxiation due to constriction of the airways and swelling of the epiglottis may occur,
immediate suppression of Anita’s hyperactive response is warranted. Subcutaneous injection of
epinephrine will bring the most immediate effect, not corticosteroids, antihistamines, antibiotics,
or nonsteroidal anti-inflammatory agents. Epinephrine will relax bronchial constriction, stimulate
the heart, and induce the reformation of tight junctions between vascular endothelial cells, which
will alleviate swelling and restore blood pressure.
14–44 Anita was suffering from acute anaphylactic shock almost certainly caused by an allergic
reaction to something she had just eaten at the buffet. Given that it was a dessert buffet, nuts or
peanuts would be one of the most likely suspects, because they or their oils are ingredients or
11
contaminants in many prepared foods, and they are well known to provoke severe anaphylactic
reactions in susceptible people.
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