40
4. The following mechanism(s) may be involved in the clinical efficacy of desensitization therapy
to treat patients with allergies to known allergens:
A. enhanced production of IgG, which binds allergen before it reaches mast cells
B. skewing of T cell responses from TH2 to TH1
C. decreased sensitivity of mast cells and basophils to degranulation by allergen
D. decreased production of IgE antibody
E. All of the above.
5. Immediate hypersensitivity skin reactions
A. usually occur within 24 hours.
B. exhibit a raised wheal due to infiltration by mononuclear cells.
C. exhibit a red flare due to vasodilation.
D. cannot be elicited by monovalent haptens.
E. All are correct.
6. Mast cells
A. are found circulating in the blood.
B. release their granules following lysis.
C. are basophilic after complete degranulation.
D. are very similar to basophils.
E. All are correct.
7. Antihistamines
A. bind to receptors for histamine, thereby preventing the histamine from exerting a
pharmacologic effect.
B. are more effective given before, rather than after, the onset of allergic symptoms.
C. do not influence the activity of leukotrienes.
D. do not affect binding of IgE to mast cells.
E. All are correct.
8. In the RAST assay for ragweed pollen
A. the patient's serum is first mixed with a radiolabeled anti-IgE.
B. only IgE anti-ragweed antibodies are detected.
C. the patient's serum competitively inhibits binding of the anti-IgE.
D. monovalent IgE is used.
E. complement is utilized.

41
9. Which of the following statements is false?
A. IL-4 and IL-13 produced by TH2 cells play a key role in regulating IgE responses.
B. Interferon-produced by TH1 cells can downregulate IgE responses.
C. In normal individuals, a balance between TH1-derived and TH2-derived cytokines helps to
maintain normal levels of IgE.
D. IL-4 levels are higher in atopic patients.
E. In IL-4 knockout mice, IgE production is normal following their exposure to parasites
due to the regulatory activity of IL-13.
10. Anaphylactic reactions
A. evolve in minutes and abate within 30 minutes.
B. may be followed by inflammatory sequelae hours later.
C. are the consequences of released pharmacologic agents.
D. may involve components of mast-cell granule matrix.
E. All of the above.
__________________________________________________ __________________________
Case Study
While playing tennis on a warm day, a young man felt a wasp on his arm and brushed it off, but still
received a mild sting, which he ignored. Ten minutes later he felt dizzy and began to itch under his arms
and on his scalp. When he broke out in hives and felt a tightness in his chest, he headed for the hospital.
On the way he felt cold and clammy, and collapsed on the seat of the taxi. In the emergency unit, his
pulse was barely detectable. What happened and why?


42
Chapter 14: Hypersensitivity Reactions: Antibody-Mediated (Type I) Reactions
Answers to Review Questions
1. B Allergic (also known as atopic) individuals have already made IgE responses to specific
allergens. IgE binds passively to cells expressing high-affinity Fc receptors for IgE (e.g., mast
cells) and interacts with the allergen when present. This results in cross-linking of the high-affinity
FcR, resulting in mast-cell degranulation. The allergen does not need to be processed
by APCs in order to bind to IgE.
2. E All are effects of epinephrine, and make it useful for treatment of acute anaphylactic
symptoms.
3. C Since the IgE Fc fragments would bind to the high-affinity FcR expressed on the surface
of mast cells, the allergen-specific IgE would not have access to these receptors and, therefore,
would not bind to these cells. When the allergen is introduced intradermally, while it would bind
to the allergen-specific IgE at the site, this would not result in cross-linking of FcR, which are
saturated with soluble IgE Fc fragments. Hence no immediate hypersensitivity reaction would
take place.
4. E All are considered to be involved to varying degrees in injection therapy.
5. E All are correct statements.
6. D Mast cells release granules physiologically and not by lysing, they are basophilic before
but not after they degranulate, and they are not found circulating freely. Mast cells are similar to
circulating basophils.
7. E All are correct statements.
8. B The RAST assay measures IgE antibody that is allowed to bind to allergen coupled to an
insoluble matrix. It detects IgE anti-ragweed antibodies. It does not utilize monovalent IgE, and
complement is not utilized in the test.
9. E IL-4 knockout mice do not make IgE responses when challenged with parasites, such as
Nippostrongylus brasiliensis. This finding is consistent with the fact that IL-4 plays a key role in
the regulation of IgE responses by B cells.
10. E All are true. A and C are true of the classic "wheal and flare" type response, while B and
D describe features of the "late-phase" response, which is a complication of some anaphylactic
reactions.
__________________________________________________ __________________________
Answer to Case Study
This is a classic case of systemic anaphylaxis. In the emergency room, epinephrine was promptly
administered and the symptoms due to vascular permeability (hives, low blood pressure), and smooth
muscle constriction (difficulty in breathing) were reversed. When he revived sufficiently, he revealed


43
that he had been stung by similar-looking insects in the past, the last time 3 months ago, but without any
noticeable effects. These stings were apparently the priming injections building up sufficient levels of
IgE antibody to sensitize his mast cells. Thus the last sting, despite the fact that little venom was
injected, was sufficient to precipitate a systemic reaction. A careful skin test, involving intradermal
injection of very dilute wasp venom, should show an immediate "wheal and flare" response, confirming
the existence of sensitivity. The young man should be advised to (1) avoid wasps, (2) carry an
emergency vial of injectable epinephrine, and (3) undergo desensitization therapy aimed at
hyposensitization to the wasp venom antigen.


44
Chapter 15: Hypersensitivity Reactions: Antibody-Mediate (Type II) Cytotoxic Reactions and
Immune Complex (Type III) Reactions
Review Questions
For each question, choose the ONE BEST answer or completion.
1. Which of the following clinical diseases is most likely to involve a reaction to a hapten in its
etiology?
A. Goodpasture's syndrome
B. hemolytic anemia after treatment with penicillin
C. rheumatoid arthritis
D. farmer's lung
E. Arthus reaction
2. An IgA antibody to a red blood cell antigen is unlikely to cause autoimmune hemolytic anemia
because
A. it would be made only in the gastrointestinal tract.
B. its Fc region would not bind receptors for Fc on phagocytic cells.
C. it can fix complement only as far as C1, C4, C2.
D. it has a too-low affinity.
E. it requires secretory component to work.
3. The glomerular lesions in immune complex disease can be visualized microscopically with a
fluorescent antibody against
A. IgG heavy chains.
B. light chains.
C. C1.
D. C3.
E. All of the above.
4. The lesions in immune complex-induced glomerulonephritis.
A. are dependent on erythrocytes and complement.
B. result in increased production of urine.
C. require both complement and neutrophils.
D. are dependent on the presence of macrophages.
E. require all nine components of complement.


45
5. Serum sickness occurs only
A. when anti-basement membrane.
B. in cases of extreme excess of antibody.
C. when IgE antibody is produced.
D. when soluble immune complexes are formed.
E. in the absence of neutrophils.
6. Immune complexes are involved in the pathogenesis of
A. poststreptococcal glomerulonephritis.
B. pigeon breeder's disease.
C. serum sickness.
D. an edematous hemorrhagic reaction in the skin of a beekeeper, 2 hours after he was stung
for the 20 th time.
E. All of the above.
7. The Arthus reaction and farmers' lung differ because
A. only the former is due to antigen-antibody complexes.
B. the mode of contact with the antigen is different.
C. only the former requires complement.
D. only the latter can occur in farmers.
E. the reactions in farmer's lung are much more rapid.
8. The final damage to vessels in immune complex-mediated arthritis is due to
A. cytokines produced by T cells.
B. histamine and SRS-A.
C. the C5, C6, C7, C8, C9 membrane attack complex.
D. lysosomal enzymes of polymorphonuclear leukocytes.
E. cytotoxic T cells.
9. Serum sickness is characterized by
A. deposition of immune complexes in blood vessel walls when there is a moderate excess
of antigen.
B. phagocytosis of complexes by granulocytes.
C. consumption of complement.
D. appearance of symptoms before free antibody can be detected in the circulation.
E. All of the above.
10. Type II hypersensitivity
A. is antibody-independent.
B. is complement-independent.
C. is mediated by CD8 + T cells.
D. requires immune complex formation.
E. involves antibody-mediated destruction of cells.

46
11. A patient is suspected of having farmer's lung. A provocation test involving the inhalation of an
extract of moldy hay is performed. A sharp drop in respiratory function is noted within 10
minutes and returns to normal in 2 hours, only to fall again in another 2 hours. The most likely
explanation is that
A. the patient has existing T cell-mediated hypersensitivity.
B. this is a normal pattern for farmer's lung.
C. the patient developed a secondary response after the inhalation of antigen.
D. the symptoms of farmer's lung are complicated by an IgE-mediated reactivity to the same
antigen.
E. All of the above.
__________________________________________________ __________________________
Case Study
A technician in a snake venom-producing farm got careless one day and was bitten by a rare lethal
Egyptian cobra. He was rushed to the emergency department, and a call went out immediately for
antivenom serum. Fortunately some was located, and within 5 hours he was given 15 ml intravenously.
The next day he received another 10 ml, the last available. Within days he was well on the way to
recovery and left the hospital a week later. He returned 10 days after leaving the hospital complaining
of joint pain, fever, and recurrent itchy hives on his trunk, arms, and legs. What do you suspect is
happening, and how would you confirm it?

47
Chapter 15: Hypersensitivity Reactions: Antibody-Mediate (Type II) Cytotoxic Reactions and
Immune Complex (Type III) Reactions
Answers to Review Questions
1. B Penicillin can function as a hapten, binding to red blood cells and inducing a hemolytic
anemia. A, C, and D are examples of immune aggregate (type III) reactions requiring
complement and neutrophils for pathologic effects.
2. B Since phagocytic cells have Fc receptors for IgG, bound IgA would not cause engulfment
and damage. Thus, A, C, D, and E are false.
3. E The lesions in immune complex disease are dependent on the presence of antigen,
antibody, and complement. Hence all can be demonstrated by immunofluorescence at a lesion:
A and B, because they are parts of IgG; C and D, because they are the early components of
complement activated by the immune aggregated.
4. C Damage by immune complexes requires complement components to attract neutrophils,
which are the agents responsible for subsequent tissue damage. Lysis by the final sequence of
C6, C7, C8, and C9 is not required.
5. D Anti-basement membrane antibodies may produce damage, but can be distinguished from
serum sickness lesions by their ribbonlike appearance compared to the lumpy-bumpy appearance
of serum sickness lesions. Excess of antibody would clear antigen rapidly with few lesions. IgE
antibody is responsible for anaphylactic reactions, and neutrophils are required for the lesions
typical of serum sickness.
6. E All are examples of type III hypersensitivity reactions: A, by production of antibody,
which reacts with normal kidney antigen; B, by inhalation of antigens from pigeon droppings; C,
serum sickness is a classical example of an immune complex disease; and D is a description of
an Arthus reaction in someone who has been immunized by repeated injection of bee venom.
7. B Both the Arthus reaction and farmer's lung are examples of immune aggregate reactions
that require complement and neutrophils. The former involves antigen injected into the skin; the
latter involves inhaled antigen.
8. D Neither T cells nor mast cells are responsible for the final tissue damage in immune
complex disease. Therefore A, B and E are eliminated. The final lytic complex of complement
is similarly not involved, since complement activation up to C5 is sufficient to bring in the
polymorphonuclear leukocytes, whose lysosomal enzymes cause the tissue damage.
9. E All are characteristics of serum sickness.
10. E Type II hypersensitivity reactions occur following development of antibodies against
target antigens expressed on normal cells or cells with altered membrane determinants.
Antibodies bind to the surface of these cells and mediate damage or destruction by one or more
mechanisms, including complement-mediated reactions. CD8 + cytotoxic T cells and immune
complexes are not involved in these reactions.

48
11. D The type III response in farmer's lung and similar occupational diseases has an onset of
symptoms usually several hours after exposure. The appearance of breathing difficulties within
minutes could create a strong suspicion that a type I anaphylactic response is also present.
Presumably, the patient made both IgE and IgG antibodies to the actinomycete antigens. A
positive wheal and flare reaction on skin testing would provide further confirmation.
__________________________________________________ __________________________
Answer to Case Study
Most antivenoms of exotic species such as snake, spider, and scorpion would be made in horses. The
horse antiserum neutralized the toxin and saved the patient's life. However, being a foreign protein, it
induced an immune response with resultant formation of antigen-antibody complexes in joints and the
activation of complement to give anaphylatoxins were responsible for the join pain, hives, and itching he
experienced. It is possible that he could subsequent develop symptoms of glomerulonephritis as well.
Treatment would consist of corticosteroid administration for its general antiinflammatory effects.
Confirmatory studies of your diagnosis might include looking for depressed levels of serum C3 and C4
as a result of activation in tissue by the antigen-antibody aggregates. In the convalescent stage, one
might also find antibody to horse Ig as a final definitive proof of your diagnosis.

49
Chapter 16: Hypersensitivity Reactions: T-Cell-Mediated,
Type IV -- Delayed-Type Hypersensitivity
Review Questions
For each question, choose the ONE BEST answer or completion.
1. Which of the following does not involve cell-mediated immunity?
A. contact sensitivity to lipstick
B. rejection of a liver graft
C. serum sickness
D. tuberculin reaction
E. immunity to chicken pox
2. A positive delayed-type hypersensitivity skin reaction involves the interaction of
A. antigen, complement, and cytokines.
B. antigen, antigen-sensitive lymphocytes, and macrophages.
C. antigen-antibody complexes, complement, and neutrophils.
D. IgE antibody, antigen, and mast cells.
E. antigen, macrophages, and complement.
3. Cell-mediated immune responses are
A. enhanced by depletion of complement.
B. suppressed by cortisone.
C. enhanced by depletion of T cells.
D. suppressed by antihistamine.
E. enhanced by depletion of macrophages.
4. Delayed skin reactions to an intradermal injection of antigen may be markedly decreased by
A. exposure to a high dose of X-irradiation.
B. treatment with antihistamines.
C. treatment with an antineutrophil serum.
D. removal of the spleen.
E. decreasing levels of complement.
5. Patients with DiGeorge syndrome who survive beyond infancy would be capable of
A. rejecting a bone marrow transplant.
B. mounting a delayed-type hypersensitivity response to dinitrochlorobenzene.
C. resisting intracellular parasites.
D. forming antibody to T-dependent antigens.
E. All of the above.
F. None of the above.


50
6. Which of the following statements is characteristic of contact sensitivity?
A. The best therapy is oral administration of the antigen.
B. Patch testing with the allergen is useless for diagnosis.
C. Sensitization can be passively transferred with serum from an allergic individual.
D. Some chemicals acting as haptens induce sensitivity by covalently binding to host
proteins acting as carriers.
E. Antihistamines constitute the treatment of choice.
7. Positive skin tests for delayed-type hypersensitivity to intradermally injected antigens indicate
that
A. a humoral immune response has occurred.
B. a cell-mediated immune response has occurred.
C. both T cell and B cell systems are functional.
D. the individual has previously made IgE responses to the antigens.
E. immune complexes have been formed at the injection site.
8. T cell-mediated immune responses can result in
A. formation of granulomas.
B. induration of the reaction site.
C. rejection of a heart transplant.
D. eczema of the skin in the area of prolonged contact with a rubberized undergarment.
E. All of the above.
__________________________________________________ __________________________
Case Study
As a member of an anthropologic research team, you have occasion to visit a primitive tribe in the
remote reaches of the Amazon jungle. During your visit the natives conduct a ceremony celebrating the
rites of passage for young males. This consists, among other things, of covering their bodies with
elaborate patterns of stripes and circles using a variety of colors extracted from local plants. On your
return 3 weeks later, you are asked to look at a young male who has developed alarmingly itchy and
weepy red areas of skin that run in sharply demarcated stripes across his back and on one arm.
Remembering your introductory course in immunology, you make an educated guess as to the cause.
How, under such primitive conditions, could you confirm your diagnosis?


51
Chapter 16: Hypersensitivity Reactions: T-Cell-Mediated,
Type IV -- Delayed-Type Hypersensitivity
Answers to Review Questions
1. C Serum sickness is an example of those reactions mediated by an antibody-antigen
complex that involves components of the complement system and neutrophils. All others
involve cell-mediated immunity to a significant extent.
2. B Cell-mediated reactions result from the triggering of T cells by antigen with recruitment
of macrophages. Neither antibody, complement, nor mast cells plays a role in this process,
although they do play a role in immediate hypersensitivity responses.
3. B Cortisone has a general antiinflammatory effect and is also lytic for some T cells.
Complement plays no role, and antihistamines have little effect on this type of response.
Depletion of T cells or macrophages would suppress, not enhance, this type of response, since
the response is dependent on these cells.
4. A High doses of X-irradiation will destroy T cells, which are responsible for initiating the
response. Histamine, neutrophils, spleen, and complement do not play a role, and any treatment
that affects them would not affect a DTH response.
5. F Patients with DiGeorge syndrome have a congenital thymic aplasia and lack all T cell
functions. Since A, B, and C are all aspects of a cell-mediated immune response, they would be
absent. Additionally, formation of antibody against these antigens is dependent on helper T cells
and, therefore, would not occur in these patients.
6. D Patch testing consists of application of the offending allergen under an occlusive
dressing, and a positive DTH response after 24-48 hours is considered evidence of sensitivity;
thus B is wrong. The allergens involved are those capable of penetrating skin and binding to
host carrier proteins; thus D is correct. Oral ingestion of antigen, which in certain experimental
situation, was shown to be an effective therapeutic maneuver in humans; thus A is wrong.
Corticosteroids, not antihistamines, constitute the treatment of choice for contact sensitivity; thus
E is also incorrect. Passive transfer of cell-mediate immune responses is accomplished with T
cells, not with serum, thus C is wrong.
7. B A delayed-type hypersensitivity reaction, evidenced by erythema and induration within
24-72 hours of antigen injection, indicates that a cell-mediated reaction has occurred. Such
reactions do not involve antibody produced by B cells, thus A, C, D, and E are incorrect.
8. E All of these effects are manifestations of cell-mediated immunity. Induration usually
takes place at the reaction site. Formation of granulomas is characteristic of a chronic DTH
reaction. Rejection of the heart is an example of an allograft response. Some of the chemicals
used to cure rubber can induce contact sensitivity after prolonged exposure of the skin to them.

52
Answer to Case Study
The appearance of the skin lesion and its sharp demarcations and weepy, itchy nature all suggest contact
sensitivity. One of the dyes used to paint the body is most likely the sensitizer and, since it persisted on
the skin, was also able to provoke a T cell-mediated reaction after the initial expansion of the specific
clones. In the absence of sophisticated testing equipment, a simple patch test using samples of the
various dyes applied to healthy areas of skin should show a localized contact reaction 24-48 hours later
at the site to which the causative dye was applied. (In the laboratory one might also look for an in vivo
proliferative response of the patient's peripheral blood lymphocytes to added dye. A biopsy of the lesion
should reveal an intense infiltrate of mononuclear cells.)


53
Chapter 17: Autoimmunity
Review Questions
For each question, choose the ONE BEST answer or completion.
1. Most autoimmune diseases are caused by
A. single genetic defect.
B. known infectious organism.
C. constellation of genetic and environmental events.
D. hormonal dysregulation.
E. B-cell defect.
2. Identifying an autoimmune disease in humans is often accomplished by
A. finding an antibody against self-components.
B. passively transferring specific T cells from a patient to a healthy individual.
C. showing that T cells or antibodies are the cause of the tissue damage.
D. circumstantial evidence, such as MHC association and clinical improvement, with
immunosuppressive drugs.
E. finding the definitive agent or agents responsible for the disease.
3. The following is/are possible mechanism(s) for the recognition of self-components by the
immune system in autoimmune diseases:
A. alteration of a self-antigen so it is recognized as foreign
B. leakage of sequestered self-antigen
C. loss of suppressor cells
D. infection with a microorganism that carries a cross-reactive antigen
E. Any of the above.
4. Rheumatoid factor, found in synovial fluid of patients with rheumatoid arthritis, is most
frequently found to be
A. IgM reacting with L chains of IgG.
B. IgM reacting with H-chain determinants of IgG.
C. IgE reacting with bacterial antigens.
D. antibody to collagen.
E. antibody to DNA.
5. The pathology in autoimmune diseases due to antibody may be a result of
A. the formation of antigen-antibody complexes.
B. antibody blocking a cell receptor.
C. antibody-induced phagocytosis.
D. antibody-induced complement mediated lysis.
E. Any of the above.


54
6. Autoimmune hemolytic anemia:
A. is usually due to warm agglutinins belonging to the IgM class directed against Rh
antigens on red blood cells.
B. may be due to the production of either cold agglutinins after viral infection or
autoantibodies following drug treatment.
C. is the result of cytotoxic T cells lysing red blood cells.
D. does not generally involve complement components in red blood cell lysis.
E. can be characterized by a negative Coombs test.
7. Systemic lupus erythematosus
A. is due to a mutation in double-stranded DNA.
B. is a classic example of a T-cell-mediated autoimmune disease.
C. has multiple symptoms and affects many organs.
D. results from antibodies specific to thyroid.
E. affects only skin epithelial cells.
8. Diseases in with TH1 cells and cytotoxic CD8 + T cells probably play major roles in their
pathology include all of the following except
A. myasthenia gravis.
B. Hashimoto's thyroiditis.
C. rheumatoid arthritis.
D. multiple sclerosis.
E. insulin-dependent diabetes mellitus.
9. A patient is found to have a form of diabetes in which his immune system is destroying his
pancreatic islet cells. Which is the most likely explanation for this disease state?
A. The patient has an acquired immunodeficiency syndrome.
B. Immune complex formation and complement are the main contributors to insulitis.
C. In the islets of the pancreas, cells have upregulated MHC class II and Fas molecules,
making them susceptible to cell death by immune cells.
D. There is an increase in suppressor cells.
E. CD4 + T cells are being destroyed by pancreatic enzymes.
10. Hashimoto's thyroiditis
A. is due primarily to antibodies formed to thyroid-stimulating hormone receptors.
B. mimics an animal model in which the disease is induced by immunization with
thyroglobulin.
C. can be transplacentally transmitted causing a neonatal form of the disease.
D. is an autoimmune disease which affects males and females equally.
E. is characterized by immune complex deposition in the thyroid.
55
Case Study
A 17-year-old boy suffered an injury to his left eye when, during a car crash, a sharp sliver of glass
penetrated his eye, damaging his lens and uveal tract. The glass was removed and the injury repaired
with complete recovery. However, 3 weeks later he noticed some redness in the left eye and
photophobia, followed by pain and severe visual impairment. The left eye was removed, and histologic
examination showed an extensively infiltrated uveal tract with abundant lymphocytes and mononuclear
cells. Two weeks later the other eye began to show the same symptoms. What is going on, and what
could be done?


56
Chapter 17: Autoimmunity
Answers to Review Questions
1. C The etiologies of most autoimmune diseases appear to be multifactorial and require a
combination of genetic and environmental events to manifest themselves.
2. D For most human autoimmune disease circumstantial evidence is used. Merely finding an
antibody to self-components does not imply that there is a disease condition. T cells or
antibodies are the cause of tissue damage in many diseases, such as infectious disease, and does
not necessarily mean that the disease is an autoimmune one. Passive transfer of T cells is
difficult in humans and in most autoimmune diseases, no definitive agent or agents have been
identified. The best answer is D.
3. E Self-reactive T and B cells may be activated by any of the mechanisms listed.
4. B Rheumatoid factor is generally an IgM antibody that reacts with Fc determinants on the H
chain.
5. E All are possible causes of antibody-induced autoimmune disease.
6. B Warm agglutinins belong to the IgG class; cytotoxic T cells are not known to cause
autoimmune hemolytic anemia; complement is a frequent participant in lysis or opsonization; the
Coombs test is frequently positive for either IgG, IgM or C3 in patients with autoimmune
hemolytic anemia.
7. C Systemic lupus erythematosus affects skin, kidneys, heart, and joints. Symptoms are due
to immune complexes that lodge in those areas and induce damage via activation of complement
and infiltration of leukocytes. DNA may be involved as an antigen, but mutation plays no role,
and the disease is initiated primarily by antibodies and is not considered a classic T-cell disease.
8. A Antibody has been implicated in myasthenia gravis both from experimental animal
models and the fact that neonatal form can be transferred through the placenta from mother to
baby. The other diseases listed are primarily cell mediated by effector T cells.
9. C One of the currently favored mechanisms for type 1 diabetes is an autoimmune response
in which CD4 + TH1 cells specific for islet cells which have upregulated the expression of MHC
class II molecules become activated and participate in the inflammatory reaction. Cytotoxic T
cells and other immune cells cause the death of the cells leading to insulin-dependent diabetes.
10. B Hashimoto's thyroiditis is thought to be a T-cell-mediated disease, some features of
which can be found in an experimental model by immunization of animals with thyroglobulin in
adjuvant.
56
Chapter 17: Autoimmunity
Answers to Review Questions
1. C The etiologies of most autoimmune diseases appear to be multifactorial and require a
combination of genetic and environmental events to manifest themselves.
2. D For most human autoimmune disease circumstantial evidence is used. Merely finding an
antibody to self-components does not imply that there is a disease condition. T cells or
antibodies are the cause of tissue damage in many diseases, such as infectious disease, and does
not necessarily mean that the disease is an autoimmune one. Passive transfer of T cells is
difficult in humans and in most autoimmune diseases, no definitive agent or agents have been
identified. The best answer is D.
3. E Self-reactive T and B cells may be activated by any of the mechanisms listed.
4. B Rheumatoid factor is generally an IgM antibody that reacts with Fc determinants on the H
chain.
5. E All are possible causes of antibody-induced autoimmune disease.
6. B Warm agglutinins belong to the IgG class; cytotoxic T cells are not known to cause
autoimmune hemolytic anemia; complement is a frequent participant in lysis or opsonization; the
Coombs test is frequently positive for either IgG, IgM or C3 in patients with autoimmune
hemolytic anemia.
7. C Systemic lupus erythematosus affects skin, kidneys, heart, and joints. Symptoms are due
to immune complexes that lodge in those areas and induce damage via activation of complement
and infiltration of leukocytes. DNA may be involved as an antigen, but mutation plays no role,
and the disease is initiated primarily by antibodies and is not considered a classic T-cell disease.
8. A Antibody has been implicated in myasthenia gravis both from experimental animal
models and the fact that neonatal form can be transferred through the placenta from mother to
baby. The other diseases listed are primarily cell mediated by effector T cells.
9. C One of the currently favored mechanisms for type 1 diabetes is an autoimmune response
in which CD4 + TH1 cells specific for islet cells which have upregulated the expression of MHC
class II molecules become activated and participate in the inflammatory reaction. Cytotoxic T
cells and other immune cells cause the death of the cells leading to insulin-dependent diabetes.
10. B Hashimoto's thyroiditis is thought to be a T-cell-mediated disease, some features of
which can be found in an experimental model by immunization of animals with thyroglobulin in
adjuvant.
58
Chapter 18: Immunodeficiency and Other Disorders of the Immune System
Review Questions
For each question, choose the ONE BEST answer or completion.
1. An 8-month-old baby has a history of repeated gram-positive bacterial infections. The most
probably cause for this condition is that
A. the mother did not confer sufficient immunity on the baby in utero.
B. the baby suffers from erythroblastosis fetalis (hemolytic disease of the newborn).
C. the baby has a defect in the alternative complement pathway.
D. the baby is allergic to the mother's milk.
E. None of the above.
2. A 50-year-old worker at an atomic plant who previously had a sample of his own bone marrow
cryopreserved was accidentally exposed to a minimal lethal dose of radiation. He was
subsequently transplanted with his own bone marrow. This individual can expect
A. to have recurrent bacterial infections.
B. to have serious fungal infections due to deficiency in cell-mediated immunity.
C. to make antibody responses to thymus-independent antigens only.
D. All of the above.
E. None of the above.
3. Which of the following immune deficiency disorders is associated exclusively with an
abnormality of the humoral immune response?
A. X-linked agammaglobulinemia (Bruton's agammaglobulinemia)
B. DiGeorge syndrome
C. Wiskott-Aldrich syndrome
D. chronic mucocutaneous candidiasis
E. ataxia telangiectasia
4. A sharp increase in levels of IgG, with a spike in the IgG region seen in the electrophoretic
pattern of serum proteins is an indication of
A. IgA or IgM deficiency.
B. multiple myeloma.
C. macroglobulinemia.
D. hypogammaglobulinemia.
E. severe fungal infections.

59
5. Patients with DiGeorge syndrome may fail to produce IgG in response to immunization with T-dependent
antigens because
A. they have a decreased number of B cells that produce IgG.
B. they have increased numbers of suppressor T cells.
C. they have a decreased number of helper T cells.
D. they have abnormal antigen-presenting cells.
E. they cannot produce IgM during primary responses.
6. A 2-year-old child has had three episodes of pneumonia and two episodes of otitis media. All
the infections were demonstrated to be pneumococcal. Which of the following disorders is most
likely to be the cause?
A. an isolated transient T-cell deficiency
B. a combined T- and B-cell deficiency
C. a B-cell deficiency
D. transient anemia
E. The child has AIDS.
7. A healthy woman gave birth to a baby. The newborn infant was found to be HIV-seropositive.
This finding is most likely the result of
A. the virus being transferred across the placenta to the baby.
B. the baby is making anti-HIV antibodies.
C. the baby's erythrocyte antigens cross-reacting with the virus.
D. the mother's erythrocyte antigens cross-reacting with the virus.
E. maternal HIV-specific IgG being transferred across the placenta to the baby.
8. Immunodeficiency disease can result from
A. a developmental defect of T lymphocytes.
B. a developmental defect of bone marrow stem cells.
C. a defect in phagocyte function.
D. a defect in complement function.
E. All of the above.
9. A 9-month-old baby was vaccinated against smallpox with attenuated smallpox virus. He
developed a progressive necrotic lesion of the skin, muscles, and subcutaneous tissue at the site
of inoculation. The vaccination reaction probably resulted from
A. B-lymphocyte deficiency.
B. reaction to the adjuvant.
C. complement deficiency.
D. T-cell deficiency.
E. B- and T-lymphocyte deficiency.

60
10. The most common clinical consequence(s) of C3 deficiency is(are)
A. increased incidence of tumors.
B. increased susceptibility to viral infections.
C. increased susceptibility to fungal infections.
D. increased susceptibility to bacterial infections.
E. All of the above.
__________________________________________________ __________________________
Case Study
A 4-year-old child, who just moved to a new town with his mother, is brought to a pediatrician's office
with a complaint of the child's failure to thrive, including loss of appetite, weight loss, and persistent
cough. On physical examination, the child appears pale and sickly, has a low-grade fever, but no other
physical signs. His past history is unremarkable except for a fractured leg at 1 year of age that required
a blood transfusion during surgery, but it healed without complication. A battery of tests are performed
to arrive at a diagnosis. X-*** examination showed some bilateral pulmonary infiltrates. Blood count is
normal, with slightly reduced white cell numbers. An ELISA to detect serum immunoglobulins showed
elevated IgG, IgM, and IgA. Skin tests performed with mumps, tetanus, and candida antigens were
negative. Antibiotic therapy was started, but on the next visit the child was sicker and now had enlarged
lymph nodes, spleen, and liver. What diagnosis should the physician be thinking of at this point, and
how could it be confirmed?


61
Chapter 18: Immunodeficiency and Other Disorders of the Immune System
Answers to Review Questions
1. E None of the above is likely to be the underlying cause for the history. The baby is
probably hypogammaglobulinemic. Hypogammaglobulinemia leads to recurrent bacterial
infections. Viral and fungal infections are controlled by cell-mediated immunity, which is
normal in hypogammaglobulinemic individuals. Answer A is incorrect because the mother's
IgG, which passed through the placenta, would have a half-life of 23 days, and would, therefore,
not be expected to remain in the baby's circulation for 8 months. At this age any Ig present in the
baby's circulation is synthesized by the baby. Answer B is irrelevant, since erythroblastosis
fetalis is caused by the destruction of the newborn's Rh + erythrocytes by the Rh - mother's
antibodies to Rh antigen. Answer C is unlikely since the classical complement pathway would
still be protective; moreover, a defect in the alternative pathway would not result in the selective
inability to protect from only gram-positive bacterial infections. Answer D is incorrect since,
even if allergic to the mother's milk, the baby should not suffer from increased frequency of
bacterial infections.
2. E The autologous bone marrow cells, which contain stem cells, will replicate, differentiate,
and repopulate the hematopoietic-reticuloendothelial system, rendering the individual
immunologically normal. As such, the individual is not expected to have bacterial, viral, or
fungal infections, or respond to antigens differently from a normal individual.
3. A The only immune deficiency disorder that is associated with abnormality exclusively of
the humoral response is Bruton's agammaglobulinemia or X-linked agammaglobulinemia.
DiGeorge syndrome results from thymic aplasia, where there is a deficiency in T cells that may
influence the IgG responses, which require helper T cells. Wiskott-Aldrich syndrome is
associated with several abnormalities. Ataxia telangiectasia is a disease with defects in both
cellular and humoral immune responses although T-cell-dependent areas of lymphoid tissues are
most severely affected. Chronic mucocutaneous candidiasis is a poorly defined collection of
syndromes associated with a selective defect in the functioning of T cells.
4. B This pattern is characteristic of multiple myeloma (IgG myeloma). Multiple myeloma
may be recognized by the synthesis of large amounts of homogeneous antibody of any one
isotype. Although patients with multiple myeloma may suffer from a decreased synthesis of
other Ig isotypes, the electrophoretic pattern is not necessarily an indication of IgA or IgM
deficiency.
5. C Patients with DiGeorge syndrome have a decreased number of T cells--in particular,
helper T cells, which are essential for the IgG response to T-dependent antigens. These patients
have normally functioning B cells and are capable of responding to T-independent antigens, or
with only IgM responses (primary responses) to T-dependent antigens.


61
Chapter 18: Immunodeficiency and Other Disorders of the Immune System
Answers to Review Questions
1. E None of the above is likely to be the underlying cause for the history. The baby is
probably hypogammaglobulinemic. Hypogammaglobulinemia leads to recurrent bacterial
infections. Viral and fungal infections are controlled by cell-mediated immunity, which is
normal in hypogammaglobulinemic individuals. Answer A is incorrect because the mother's
IgG, which passed through the placenta, would have a half-life of 23 days, and would, therefore,
not be expected to remain in the baby's circulation for 8 months. At this age any Ig present in the
baby's circulation is synthesized by the baby. Answer B is irrelevant, since erythroblastosis
fetalis is caused by the destruction of the newborn's Rh + erythrocytes by the Rh - mother's
antibodies to Rh antigen. Answer C is unlikely since the classical complement pathway would
still be protective; moreover, a defect in the alternative pathway would not result in the selective
inability to protect from only gram-positive bacterial infections. Answer D is incorrect since,
even if allergic to the mother's milk, the baby should not suffer from increased frequency of
bacterial infections.
2. E The autologous bone marrow cells, which contain stem cells, will replicate, differentiate,
and repopulate the hematopoietic-reticuloendothelial system, rendering the individual
immunologically normal. As such, the individual is not expected to have bacterial, viral, or
fungal infections, or respond to antigens differently from a normal individual.
3. A The only immune deficiency disorder that is associated with abnormality exclusively of
the humoral response is Bruton's agammaglobulinemia or X-linked agammaglobulinemia.
DiGeorge syndrome results from thymic aplasia, where there is a deficiency in T cells that may
influence the IgG responses, which require helper T cells. Wiskott-Aldrich syndrome is
associated with several abnormalities. Ataxia telangiectasia is a disease with defects in both
cellular and humoral immune responses although T-cell-dependent areas of lymphoid tissues are
most severely affected. Chronic mucocutaneous candidiasis is a poorly defined collection of
syndromes associated with a selective defect in the functioning of T cells.
4. B This pattern is characteristic of multiple myeloma (IgG myeloma). Multiple myeloma
may be recognized by the synthesis of large amounts of homogeneous antibody of any one
isotype. Although patients with multiple myeloma may suffer from a decreased synthesis of
other Ig isotypes, the electrophoretic pattern is not necessarily an indication of IgA or IgM
deficiency.
5. C Patients with DiGeorge syndrome have a decreased number of T cells--in particular,
helper T cells, which are essential for the IgG response to T-dependent antigens. These patients
have normally functioning B cells and are capable of responding to T-independent antigens, or
with only IgM responses (primary responses) to T-dependent antigens.

62
6. C The cause for the described case history is very likely due to B-cell deficiency, which is
characterized by recurrent bacterial infections leading to otitis media and pneumonia. T-cell
deficiency would usually result in viral, fungal, and protozoal infections. The same is true for
combined T- and B-cell deficiency. Answer D (transient anemia) is irrelevant in this case--
anemia is not generally associated with increased infections. It is unlikely that with a history of
only pneumococcal infections, the child would have AIDS. The latter syndrome is associated
more with characteristic infections such as with Pneumocystis carinii and various viral
infections.
7. E The most likely explanation is that the "healthy" mother has been infected with HIV-1
and is making anti-HIV IgG, which is transferred to the fetus and newborn transplacentally.
While it is possible that the HIV was transferred to the infant across the placenta, this would not
cause the newborn to make antibodies to the virus at this young age--thus answers A and B are
incorrect. Answers C and D are false because this unlikely situation would result in the
recognition of the viral antigen as "self" and the individual would not make anti-self antibodies.
8. E All are correct. Immunodeficiency disorders may result from defects in the development
of bone marrow stem cells into lymphocytes and other cells that participate in the immune
response. They can also result from defects in phagocyte functions, which are important in
phagocytosis and presentation of antigen. Immunodeficiency disorders may also result from
defects in complement function--an absence or malfunction of one or more of the complement
components, their activators, or regulators.
9. D T-cell deficiency would result in the absence of the crucial immunologic defenses against
viral infection, that is, cell-mediated immunity. Cell-mediated immunity plays the major role in
immunity to viral infections, much greater than the roles of antibody or complement. In fact,
individuals with impaired T-cell-mediated immunity should not be vaccinated with live virus,
which, even if attenuated, may cause a serious infection.
10. D Deficiency in C3 is associated with increased susceptibility to bacterial infections, since
C3 plays an important role in the destruction of bacteria and their increased opsonization, by
participating in the classical and the alternative pathways of complement activation. Cell-mediated
immunity (CMI) is generally more important in the resistance of the host to viral and
fungal infections. Also, in general, CMI is considered to be more important than complement in
the resistance of the host to tumors.
__________________________________________________ __________________________
Answer to Case Study
This is a possible case of childhood AIDS, presumably attributable to the earlier transfusion with blood
obtained from a blood bank. Although present-day tests to screen blood from donors are highly reliable,
there are still isolated cases of HIV transmission by blood transfusion. Following a long incubation
period, the child presented with a slightly lowered white cell count, somewhat elevated immunoglobulin
levels, but a seriously compromised T-cell function. The latter was determined by the absence of skin
reactions to mumps, tetanus toxoid, and candida antigens, all of which elicit T-cell-mediated delayed-type
hypersensitivity reactions in normal individuals. A follow-up test of the levels of circulating CD4 +
and CD8 + cells revealed a ratio of 0.4, indicating that helper CD4 + cells, the target of the HIV virus,
have declined markedly. Further study of the lung infiltrate, which failed to respond to antibiotic
therapy, would be done by bronchoscopy and lavage. Microscopic examination of the washings would

63
probably show an opportunistic organism such as Pneumocystis carinii, a common cause of death in
patients with AIDS. Final confirmatory evidence would come from an examination of the child's serum
for the presence of antibody to HIV antigens, a clear indication of an infection with HIV, and from the
use of an HIV-specific PCR to ascertain the presence of the viral genes.


64
Chapter 19: Transplantation Immunology
Review Questions
For each question, choose the ONE BEST answer or completion.
1. Kidney transplantation was performed using a kidney from a donor who was matched to the
recipient by serologic tissue typing. However, within a few months, the kidney was rejected.
Assuming no technical problems with the surgical procedure, one reason for the rejection may be
that
A. there was insufficient blood supply to the graft.
B. there could have been a mismatch, which would have been detected by a mixed
lymphocyte reaction.
C. the recipient developed blocking antibodies.
D. the recipient also suffered from Wiskott-Aldrich syndrome.
E. the donor was agammaglobulinemic.
2. Currently, the best indicator for predicting compatibility for transplantation of tissue from donor
A to recipient B is obtained by
A. one-way mixed leukocyte reaction between B cells and mitomycin C-treated A cells.
B. one-way mixed leukocyte reaction between A cells and mitomycin C-treated B cells.
C. serologic typing and cross-matching of A and B cells.
D. two-way mixed leukocyte reaction between A and B cells.
E. matching for blood group antigens.
3. The MHC contains all of the following except
A. genes that encode transplantation antigens.
B. genes that encode immunoglobulins.
C. genes that regulate immune responsiveness.
D. genes that encode some components of complement.
E. genes that encode class I and class II antigens.
4. The most common serologic test used for the detection of HLA antigens on lymphocytes is
A. the complement fixation test.
B. double gel diffusion.
C. complement-dependent cytotoxicity test.
D. mixed lymphocyte reaction.
E. radioimmunoassay.


64
Chapter 19: Transplantation Immunology
Review Questions
For each question, choose the ONE BEST answer or completion.
1. Kidney transplantation was performed using a kidney from a donor who was matched to the
recipient by serologic tissue typing. However, within a few months, the kidney was rejected.
Assuming no technical problems with the surgical procedure, one reason for the rejection may be
that
A. there was insufficient blood supply to the graft.
B. there could have been a mismatch, which would have been detected by a mixed
lymphocyte reaction.
C. the recipient developed blocking antibodies.
D. the recipient also suffered from Wiskott-Aldrich syndrome.
E. the donor was agammaglobulinemic.
2. Currently, the best indicator for predicting compatibility for transplantation of tissue from donor
A to recipient B is obtained by
A. one-way mixed leukocyte reaction between B cells and mitomycin C-treated A cells.
B. one-way mixed leukocyte reaction between A cells and mitomycin C-treated B cells.
C. serologic typing and cross-matching of A and B cells.
D. two-way mixed leukocyte reaction between A and B cells.
E. matching for blood group antigens.
3. The MHC contains all of the following except
A. genes that encode transplantation antigens.
B. genes that encode immunoglobulins.
C. genes that regulate immune responsiveness.
D. genes that encode some components of complement.
E. genes that encode class I and class II antigens.
4. The most common serologic test used for the detection of HLA antigens on lymphocytes is
A. the complement fixation test.
B. double gel diffusion.
C. complement-dependent cytotoxicity test.
D. mixed lymphocyte reaction.
E. radioimmunoassay.


65
5. Which of the following statements regarding GVH disease is incorrect?
A. GVH can result from MHC differences between donor and recipient.
B. GVH requires immunocompetent donor cells.
C. GVH may result from infusion of blood products that contain viable lymphocytes into an
immunologically incompetent recipient.
D. GVH requires natural killer cells.
E. GVH may occur in an immunosuppressed individual.
6. Transplant rejection may involve
A. cell-mediated immunity.
B. type III (immune complex) hypersensitivity.
C. complement-dependent cytotoxicity.
D. the release of IFN-.
E. All of the statements are correct.
7. Which of the following statements concerning the mixed leukocyte reaction (MLR) is correct?
A. Specific responding cells are B lymphocytes.
B. MLR results in clonal expansion of specific, alloantigen-reactive cells.
C. MLR between unrelated individuals who differ according to HLA serology is usually
negative.
D. Stimulation of proliferation is controlled primarily by the HLA-A region alleles.
E. All of the statements are correct.
8. In clinical transplantation, cytotoxic antibodies reactive against antigens expressed on the grafted
tissue
A. cause delayed rejection of the transplant.
B. are responsible for hyperacute rejection.
C. cause rejection when present in the donor.
D. are not usually directed against HLA antigens.
E. activate cytotoxic T cells, which then cause hyperacute rejection.
9. Serologic testing before kidney transplantation reveals that the leukocytes of a prospective
recipient are killed by the following anti-HLA antibodies in the presence of complement:
anti-B27, anti-A1, and anti-A3. You can conclude that
A. the prospective recipient expressed the B27, A1, and A3 HLA specificities.
B. the prospective recipient does not express the B27, A1, and A3 HLA specificities.
C. the potential donor and the prospective recipient are not siblings.
D. the potential donor and the prospective recipient are not identical twins.
E. the prospective recipient should not receive a kidney graft that expresses these HLA
specificities.

66
10. A clinical trial investigating the efficacy of a humanized anti-CD28 monoclonal antibody in
prolonging kidney allograft survival shows that patients treated with this biologic reagent have
significantly fewer episodes of chronic rejection. The probably mechanism responsible for this
effect is best explained by
A. the binding of anti-CD28 to B cells, which blocks their interaction with B7.1 and B7.2
expressed on T cells.
B. the formation of circulating CD28-anti-CD28 immune complexes.
C. the binding of anti-CD28 to T cells, which interferes with signal transduction needed for
T-cell activation.
D. the binding of anti-CD28 to suppressor T cells, which then become activated.
E. the binding of anti-CD28 to B and T cells which interferes with signal transduction and
activation of both populations.
__________________________________________________ __________________________
Case Study
A child is brought to the hospital suffering from an aplastic bone marrow after ingestion of benzene. All
blood elements are at low levels and death is imminent. The child and a sibling were rapidly typed as
both being A + Rh + , HLA-A3, 7: B4,8, and bone marrow was transfused. Within a few days the RBC
count rose, indicating a successful take. However, 3 weeks later the child began to experience diarrhea
and a skin rash on the palms and soles of the feet, spreading to the trunk. This was followed by jaundice
and enlarged liver and spleen. Administration of an anti-CD3 monoclonal antibody plus cyclosporine
produced some improvement. What went wrong, and why?


67
Chapter 19: Transplantation Immunology
Answers to Review Questions
1. B The most probably reason for the rejection is that, although serologically the donor and
recipient were matched, this was an incomplete measure. The accuracy of serologic matching is
predicated on the number of sera used in the test. There is always the possibility that a mismatch
would have been detected if additional sera was used. In genotyping by PCR, the transplantation
epitope is highly sensitive and accurate. Even the mixed leukocyte reaction is more reliable,
since it can detect mismatches that may not be detected serologically. Answer A is not correct,
since it is stated that there were no problems due to the surgical procedure. Answer C is
incorrect since blocking antibodies, if indeed developed by the recipient, would be expected to
enhance the survival of the transplant. Answer E is incorrect because the immune status of the
kidney donor is, in this case, irrelevant to the outcome of transplantation.
2. A Compatibility can be reliably predicted by the one-way mixed leukocyte reaction
between the recipient's B cells and mitomycin C-treated cells from the donor. In this test, only
the reactivity of the recipient cells against the donor antigens is measured. The reverse--that is,
reaction between A cells and mitomycin C-treated recipient B cells--is of no practical
importance, because A is not the recipient. Serologic typing and cross-matching of A and B are
of value, since those tests are more rapid than the MLR. However, there is always the possibility
that the panel of antisera used is not complete and that if more antisera were used, a mismatch
would be found. The two-way MLR is important in assessing the total degree of parity (or
disparity) in transplantation antigens, but it does not determine if the reaction is that of the donor
to the recipient cells, or of the recipient to donor cells, or both. Matching for blood group
antigens is imperative, but not sufficient. Nevertheless, if you answered D, it is also acceptable.
3. B The MHC complex contains all genes mentioned except genes that encode
immunoglobulins. They are on different chromosomes.
4. C The most common serologic test used for detection of HLA antigens on lymphocytes is
the complement-dependent cytotoxicity test. The mixed leukocyte reaction, especially the one-way
MLR, is an excellent test for HLA-D antigens, but it is a test based on cellular reactions and
not on the reaction of serum antibodies.
5. D The GVH disease is caused by the destruction of cells or tissue of an immunoincompetent
recipient by immunocompetent lymphoid cells transferred from a histoincompatible donor. The
GVH reaction does not require natural killer cells.
6. E All are correct. The important process in the rejection of an allotransplant is cell-mediated
immunity. Here, T cells, which recognize the alloantigens, become activated; the T
cells release cytokines, one of which is IFN-, which recruits and activates phagocytic cells that,
together with cytotoxic T cells, destroy the graft. However, the reaction to the allotransplant
may also involve antibodies (IgM and IgG), which can cause damage to tissue via activation of
complement and the recruitment of polymorphonuclear cells to the site of the reaction. The
polymorphonuclear cells would damage the graft by the release of their lysosomal enzymes.


68
7. B The MLR results in the clonal expansion of specific T cells, which recognize the
alloantigens in the D region of the HLA. Although clones of B cells may also expand, the major
cellular expansion is that of the T cells. The MLR between unrelated individuals who differ
according to HLA serology is usually positive (rather than negative). Thus only choice B is
correct.
8. B Cytotoxic antibodies, such as IgM and IgG, cause hyperacute rejection by complement-mediated
cell lysis or by opsonization and subsequent destruction of the transplant by phagocytic
cells. The cytotoxic antibodies may be directed against blood group antigens or to HLA antigens
on transferred cells (e.g., leukocytes); thus answer D is incorrect. The presence of cytotoxic
antibodies in the donor is usually of no clinical importance since, even if they are transferred to
the recipient with the donor's blood, they become highly diluted in the recipient. Choice E is
incorrect because cytotoxic antibodies play no role in activation of cytotoxic T cells. Thus,
choice B is correct.
9. A The demonstration that leukocytes are killed in the presence of complement when
exposed to antibodies specific for the HLA specificities listed indicates that the cells express
these determinants. Killing is due to complement-mediated cytotoxicity. Since no information
regarding the HLA phenotype of any siblings is given, choices C and D are incorrect. Choice E
is also incorrect, since it would be desirable to graft the prospective recipient with a kidney graft
that expresses these determinants. Thus, choice A is correct.
10. C Experimental models have demonstrated that injection of allografted mice with anti-CD28
monoclonal antibody does, indeed, prolong survival of the allograft. Blocking CD28
ligation interferes with the transmission of signals needed for gene expression (e.g., IL-2
synthesis) and T-cell activation. B7.1 and B7.2 are costimulatory molecules that ligate CD28
expressed on antigen-presenting cells leading to T-cell activation.
__________________________________________________ __________________________
Answer to Case Study
The symptoms are typical of GVH disease. The hasty matching presumably involved serologic typing
only and matching for MHC class II molecules by PCR genotyping, or by MLR, was not done. In
addition, care was not taken to deplete the donor bone marrow of mature T cells. Presumably,
histoincompatibility between the donor and recipient triggered the donor's T cells to attack the
recipient's cells, resulting in the symptom complex seen. Therapy aimed at destroying or inhibiting
activated donor T cells is not as effective as eliminating them in the first place.



69
Chapter 20: Tumor Immunology
Review Questions
For each question, choose the ONE BEST answer or completion.
1. The appearance of many primary lymphoreticular tumors in humans has been correlated with
A. hypergammaglobulinemia.
B. acquired hemolytic anemia.
C. BCG treatment.
D. resistance to antibiotics.
E. impairment of cell-mediated immunity.
2. Tumor antigens have been shown to cross-react immunologically in cases of
A. tumors induced by chemical carcinogens.
B. tumors induced by RNA viruses.
C. all tumors.
D. tumors induced by irradiation with ultraviolet light.
E. tumors induced by the same chemical carcinogen on two separate sites on the same
individual.
3. Which of the following is not considered a mechanism by which cytokines mediate antitumor
effects?
A. They enhance the expression of MHC class I molecules.
B. They activate LAK and TIL cells.
C. They have direct antitumor activity.
D. They induce complement-mediated cytolysis.
E. They increase activity of cytotoxic T cells, macrophages, and NK cells.
4. Rejection of a tumor may involve which of the following?
A. T-cell-mediated cytotoxicity
B. ADCC
C. complement-dependent cytotoxicity
D. destruction of tumor cells by phagocytic cells
E. All are correct.
5. Immunotoxins are
A. toxic substances released by macrophages.
B. cytokines.
C. toxins completed with the corresponding antitoxins.
D. toxins coupled to antigen-specific immunoglobulins.
E. toxins released by cytotoxic T cells.


70
6. It has been shown that a B-cell lymphoma could be eliminated with anti-idiotypic serum. The
use of this approach to treat a plasma cell tumor would not be warranted because
A. plasma cell tumors have no tumor-specific antigens.
B. plasma cell tumors are not expected to be susceptible to ADCC.
C. plasma cell tumors can be killed in vivo only by cytotoxic T lymphocytes that bear the
same A, B, and C transplantation antigens.
D. the plasma cells do not have surface Ig.
E. the idiotype on the plasma-cell surface is different from that on the B-cell surface.
__________________________________________________ __________________________
Case Study
A patient suffering from a rare cancer is treated with a cocktail of cytokines, which includes IL-2 and
IL-12 and shows improvement as measured by a reduced tumor burden, despite various side effects of
the therapy. Various functional parameters of the patient's peripheral blood cells were tested before,
during, and after therapy. An assay designed to measure macrophage phagocytic activity indicates a
significant increase in phagocytosis of antibody-opsonized bacteria one day following injection of the
cocktail. Explain what might account for this observed effect. How could you confirm your
hypothesis? Discuss how this increased phagocytic activity could be responsible for the patient's
improvement.


71
Chapter 20: Tumor Immunology
Answers to Review Questions
1. E There is a nearly 100-fold increase in the incidence of lymphoproliferative tumors in
individuals with impaired immunity, in particular with impaired cell-mediated immunity.
Hypergammaglobulinemia, acquired hemolytic anemia, or resistance to antibiotics are not
correlated with increases in lymphoproliferative tumors; neither is BCG treatment, which in
some instances has been shown to influence favorably the course of some leukemias.
2. B Immunologic cross-reactivity has been demonstrated only in cases of virally-induced
tumors (caused by either RNA or DNA viruses). Tumors induced by chemical or physical
carcinogens do not exhibit cross-reactivity, even if induced by the same carcinogen on separate
sites on the same individual.
3. D Interferon-, , and enhance the expression of class I MHC molecules on tumor cells
that makes them more vulnerable to killing by CTLs. IL-2 activates LAK and TIL cells. TNF-
and both have direct antitumor activity. IFN-increases the activity of CTLs, macrophages,
and NK cells, each of which plays an important role in tumor cell destruction. Cytokines play no
role in the activation of complement, therefore, D is incorrect.
4. E All are correct. Destruction of tumor cells may be mediated by T-cell-mediated toxicity,
by antibody-dependent cell-mediated cytotoxicity (ADCC), by complement-mediated
cytotoxicity, and by phagocytic cells, which are attracted to the tumor by T-cell lymphokines
and/or complement components, and become activated by the lymphokines or perform enhanced
phagocytosis as a result of the presence of opsonins on the target cells.
5. D Immunotoxins consist of toxic substances (or radioactive atoms) conjugated to
immunoglobulin molecules specific for tumor cells or other target cells.
6. D The only relevant statement is that plasma cells do not have surface immunoglobulins
and would, therefore, not be susceptible to treatment with anti-idiotypic antibodies. Plasma cell
tumors do have tumor-specific antigens and would be susceptible to ADCC with antibodies to
these antigens. Statemen