1.

Although fraternal twins are only as genetically similar as siblings born at

different times, they sometimes share circulation. This might lead to a form of
which of the following?
a. peripheral tolerance.
b. neonatal tolerance.
c. congenital immunodeficiency.
d. molecular mimicry.

Answer: b. Organisms are easily tolerized to antigens to which they have been
exposed during the development of their immune systems, including in the neonatal
period

2. Which of the following is part of the mechanism for inducing central tolerance
in B cells by clonal deletion?
a. the presence of soluble antigen.

b. the ability to undergo receptor editing.

c. the display of self antigen in a membrane-bound form.

d. the activity of a functional autoimmune regulator (AIRE) gene.

Answer: c. Clonal deletion in developing pre-B cells (or pre-T cells) is usually induced
as a result of a strong antigenic signal. Although a and b also participate in tolerizing

developing B cells, these mechanisms do not result in clonal deletion. To the best of
our knowledge AIRE is functional only in the thymus.
3. A common mechanism required for activating T or B cells in the periphery is
which of the following?
a. presentation of antigen in the context of MHC.
b. presentation of the particulate multivalent form of the antigen.
c. high avidity of the lymphocyte's receptor for the antigen.
d. interaction through costimulatory molecules as a second signal.

Answer: d. Both T and B cells need a second or costimulatory signal for activation.
Answer a is required for T cell activation only; answer b is required for T-cell
independent B-cell responses. High avidity for the antigen is a goal, not a requirement,
for activation.
4. Rejection of solid organ transplants may involve either humoral or cellmediated immunity or both. In order to prevent T cells of organ transplant
recipients from reacting to the transplanted tissue and to possibly induce
tolerance in the recipient, numerous biological therapeutic agents have been
developed and tried. Which of the following is one that might achieve that goal?
a. decoy molecule for CD28.

b. blocking antibody for CD40-CD40L.

c. BAFF inhibitor.

d. Fas inhibitor.

Answer: a. CD28 is a T-cell molecule, the binding of which will provide a costimulatory
signal to the T cell. By providing a decoy-soluble CD28 molecule, CD80 and/or CD86
expressed on an APC will not be available for T-cell binding. Blocking CD40-CD40L
will predominantly block B cell activation with some associated blockage of
macrophages (which are CD40+). Inhibiting Fas on the target cells may block their
apoptosis. BAFF is expressed on B cells.

5. A patient seeing a rheumatologist for the first time is asked to fill out forms
that include questions about family history. She recalls many family members
with arthritis, including her grandmother and great-aunt. Her mother has
systemic lupus erythematosus (SLE) with arthritis symptoms and renal disease.
Her mother's siblings are healthy, as are the patient's father and younger sister.
This family history is most suggestive of which of the following?
a. a microbial infection common to all afflicted family members.

b. X-linked Mendelian genetics.

c. an environmental exposure that her mother encountered while growing up.

d. bad luck.

e. a genetic predisposition.

Well done, you have selected the right answer.

Answer: e. Although an infection or environmental exposure may trigger the first
appearance of an autoimmune disease, this would occur on the background of
susceptible genetics. One could argue that there is certainly bad luck involved, but it
is the bad luck of the genes. The grandmother and great-aunt may have had SLE,
rheumatoid arthritis, or any other inflammatory arthritis or osteoarthritis (wear and
tear). Earlier age at onset would be suggestive evidence for inflammatory arthritis.
SLE does not follow simple Mendelian genetics (and certainly not X-linked inheritance,
although there is a strong female predominance, presumably due to hormonal
influences).

6. Injection of myelin basic protein (MBP) with adjuvant into mice produces
experimental autoimmune encephalomyelitis (EAE), an animal model of multiple
sclerosis. Pretreatment of the mice with low oral doses of MBP alone prevents
disease development. This suggests the production of which of the following?
a. blocking antibodies.

b. TH17 cells.

c. TH1 cell predominance.

d. Treg cells.

Answer: d. Oral administration of low antigen doses is an effective way of inducing

tolerance. Presumably, peripheral regulatory T cells are induced.

Hypersensitivity 1
1. A 25-year-old man was stung by a bee and had no reaction. The second time
he was stung, 6 months later, he had local swelling immediately. There was no
reaction the first time because of which of the following? [Questions 1 and 2 are
linked]
a. He was tolerant to bee venom.

b. He produced only IgM antibodies specific for bee venom.

c. He had no preformed IgE molecules specific for bee venom.

d. He had blocking IgG antibodies to bee venom.

e. He had no mast cells.

Answer: c. On first exposure, the patient is antigenically nave and will not have
preexisting IgE (or any antibodies) specific for bee venom. Therefore, there is no
immediate response.
2. This same man is stung a third time and goes into anaphylactic shock. This
severe reaction is due to which of the following?
a. a breakdown in tolerance.

b. cross-reactivity of bee venom with bacterial antigens.

c. the attenuation of the IgG levels in the time elapsed between challenges.

d. the higher titers of venom-specific IgE now present in this patient.

Answer: d. This scenario is typical. Every time the patient is reexposed, the response
is more severe. IgE is maintained on the surface of mast cells and is now present at a
higher density, poised to be cross-linked and cause mast cell degranulation. If a long
time period passes between challenges, IgE levels may decrease.
3. The most rapid effects of exposure to an allergen may be due to which of the
following?
a. leukotrienes.

b. granulocytic infiltration.

c. metabolites of arachadonic acid.

d. histamine.

Answer: d. Although all the choices have a role in type I hypersensitivity reactions,
only histamine is preformed in the mast cells and is immediately released on
degranulation.

1. An individual with hypothyroidism and blocking antibodies specific for

thyroid-stimulating hormone receptor has an autoimmune disease based on
which type of immune reaction? [Questions 1 and 2 are linked]
a. type I

b. type II

c. type III

d. type IV

Answer: b.
2. An individual with hyperthyroidism and stimulating antibodies specific for
thyroid-stimulating hormone (TSH) receptor has an autoimmune disease based
on which type of immune reaction?
a. type I

b. type II

c. type III

d. type IV

Answer: b. Both autoimmune diseases of the thyroidHashimoto (hypothyroidism)

and Graves' (hyperthyroidism) diseaseare due to autoantibodies specific for the
TSH receptor and therefore are both examples of type II hypersensitivity. In the case
of Hashimoto's, the antibody is antagonistic, and in the case of Graves', the antibody
functions like TSH itself.
3. Untreated pharyngeal infection with hemolytic streptococci may resolve but
may lead to several serious sequelae. One is carditis and a second is poststreptococcus glomerulonephritis. These are examples of which types of
hypersensitivity reactions, respectively?
a. type II and type III

b. type III and type II

c. type I and type III

d. type II and type I

Answer: a. The carditis that follows streptococcal infections is thought to be due to

cross-reactive antigens, antigens expressed on cardiomyocytes that are similar to the
bacterial antigens. The individual produces antibodies that then react with the cardiac
muscle cells (type II). An element of type IV hypersensitivity (see Chapter 17) is also
present as granulomatous type reactions form. Glomerular disease, on the other hand,
is due to the deposition of immune complexes extracellularly and is an example of
type III hypersensitivity.
4. A young adult is part of the phase III clinical trial for hepatitis B vaccine. As
part of the trial, her specific antibody titers are measured several days after
each injection. Several hours after the third injection, she suffers from joint
aches and swelling and a slight rash. On completion of the study, examination

of her records shows high titers of antibody after the first dose with
increasingly greater titers with each subsequent dose. Her adverse reaction is
most likely due to which of the following?
a. production of antibodies cross-reacting with synovial (joint) antigens and

epidermal antigens.
b. reaction to the vehicle (substance in which the viral antigen is suspended).

c. Arthus-type hypersensitivity reaction.

d. Anaphylaxis reaction.

Answer: c. The subject responded to immunization with unusually high antibody titers
and when boosted a second time (third shot) formed antigenantibody complexes that
deposited in the skin and joints.
1. The quantiferon test is based on which of the following?
a. the response of macrophages to the antigen.

b. the cytokine response of Th1 cells to their specific antigen.

c. the inability of macrophages to digest the antigen.

d. the interaction of CD4+ T cells and macrophages.

Answer: b. The quantiferon assay measures the release of IFN- from sensitized
antigen-specific Th1 cells when they encounter their specific antigen. The other
aspects of the delayed-type hypersensitivity (DTH) response listed are not measured
in this in vitro assay.
2. Organisms and agents most likely to induce a granulomatous DTH response
are characterized by which of the following?
a. They stimulate allergies.

b. They can be broken down into small peptides for stimulation.

c. They are indigestible by macrophages.

d. They bind to self proteins as carriers.

Answer: c. A granulomatous DTH-type response is the result of persistent, indigestible

material and/or organisms usually residing in the macrophages.
3. A common requirement for employment in a hospital in the United States is
an annual purified protein derivative (PPD) test. The employee has the extract
injected intradermally in his or her forearm and is told to return after which of
the following?
a. 2 hrs for reading.

b. 2 days for reading.

c. 2 weeks for reading.

d. 2 days for boosting, then 2 weeks for reading.

Answer: b. The DTH response takes 23 days to develop. This is characteristic of cellmediated immune responses, in contrast to responses measuring preexisting
antibodies (see type 1 hypersensitivity). The test measures prior exposure, so you
would not sensitize, boost, and then read.

Immunodeficiency
1. An 8-year-old girl is suffering from hyper-IgM syndrome due to a mutation in
AID. In contrast to male patients with X-linked hyper-IgM syndrome, this girl is
expected to have which of the following?
a. normal immunoglobulin responses to viral vaccines.

b. normal numbers of IgA+ plasma cells in mucosal-associated lymphoid tissue

(MALT).
c. normal T cell proliferative responses to mitogens.

d. normal DTH responses to commonly encountered fungal antigens such

as Candida.
Answer: d. Both types of hyper-IgM syndrome would have abnormally low or absent
immunoglobulin responses to vaccines (IgG) and abnormally low or absent IgA
plasma cells. Both would have normal T-cell proliferative responses to mitogens. This
female patient would have normal DTH reactions because DTH is a response that
does not involve B cells where her defect lies. Boys with X-linked hyper-IgM
syndrome, however, would have absent or low DTH responses because, like
immunoglobulin class switching, the response depends on CD40LCD40 interactions
and CD40L is absent. In the case of DTH, the interaction is between the T cell and
macrophages.
2. A patient with severe symptoms from rheumatoid arthritis is treated with antiTNF immunotherapy. This iatrogenically imposed immunodeficiency state may
lead to which of the following?
a. reactivation of latent tuberculosis (TB).

b. reactivation of hepatitis C.

c. reactivation of herpes zoster (shingles).

d. reactivation of influenza.

Answer: a. TB is controlled in the body by the formation of a granuloma, essentially

functioning by walling off the organism from the rest of the body. Granulomas are
comprised of macrophages (which cannot completely digest the organism and
therefore harbor it), CD4+ Th1 cells, and CD8+ T cells. Maintenance of this latent state

is dependent on IFN-, produced mainly by T cells, and TNF-, which is

autostimulatory to macrophages. Both cytokines activate macrophages, allowing them
to continue containing the organism. Elimination or absence of either cytokine can
result in active infection.