USMLE Immunology - Part 2

The correct answer is A. Recurrent viral infections
are a sign of T lymphocyte dysfunction.
Particularly important in the response to viral
infections are cytotoxic (CD8) T lymphocytes.
IL-2 is a cytokine secreted by helper T lymphocytes
that stimulates the growth of helper and
cytotoxic T lymphocytes. Therefore, even
though this patient may have an adequate
number of T lymphocytes, a defi ciency in IL-2
could lead to impaired cytotoxic T lymphocyte
differentiation and activation. This would result
in an increased susceptibility to viral infections.
Answer B is incorrect. IL-3 is secreted by activated
T lymphocytes and has functions similar
to granulocyte macrophage colony-stimulating
factor.
Answer C is incorrect. IL-4 is secreted by
helper T lymphocytes and promotes the growth
of B lymphocytes.
Answer D is incorrect. IL-5 is secreted by
helper T lymphocytes and promotes the differentiation
of B lymphocytes.
Answer E is incorrect. IL-8 is the major
chemotactic factor for neutrophils.

The correct answer is C. This clinician is concerned
that the fetus may have erythroblastosis
fetalis (hemolytic disease of the newborn). This
disease is mediated by maternally derived IgG
anti-Rh antibodies developed in Rh-negative
mothers that are directed at the Rh antigen
present on the fetal RBCs of a Rh-positive fetus
in a previous pregnancy. If the mother possesses
the antibodies developed from a previous
exposure to an Rh-positive fetus, they may cross
the placenta (antibodies of the IgG isotype
readily cross the placenta) and coat the fetal
RBCs of a Rh-positive fetus if the mother is
now pregnant with another Rh-positive child.
Antibody coating of the RBCs leads to phagocytosis
of RBCs (via Fc receptors) and/or destruction
of the RBCs by the complement system
and potentially fatal anemia. This
antibody-mediated cytotoxic reaction is an example
of a type II hypersensitivity reaction.
Answer A is incorrect. GVHD is a potentially
lethal side effect of bone marrow transplantation.
Answer B is incorrect. Type I hypersensitivity
reactions are antibody-mediated but require
antigen binding to IgE, which is prebound to
the surface of mast cells. Mast cell degranulation
then ensues. Examples include anaphylaxis,
asthma, hives, and local wheal and fl are.
Answer D is incorrect. Type III hypersensitivity
reactions are immune complex-mediated.
Examples include polyarteritis nodosa, glomerulonephritis,
rheumatoid arthritis, and systemic
lupus erythematosus.
Answer E is incorrect. Type IV hypersensitivity
reactions are a group of T-cell-mediated pathologies.
Examples include the tuberculin
skin test, transplant rejection, and contact dermatitis.

The correct answer is A. Antibody molecules
consist of two heavy chains and two light
chains. Interchain disulfi de bonds connect
both the heavy chains and the light chains.
Answer B is incorrect. Hydrogen bonds are
weaker than disulfi de bonds and do not connect
the antibody chains.
Answer C is incorrect. Ionic bonds are found
in chemicals such as sodium chloride but are
not responsible for holding antibody chains together.
Answer D is incorrect. Triple covalent bonds
are seen between some atoms, such as nitrogen,
but are not responsible for holding the
chains of antibody molecules together.
Answer E is incorrect. Van der Waals forces
are weak attraction forces and do not hold antibody
chains together.

The correct answer is B. Celiac sprue is also
known as gluten-sensitive enteropathy, nontropical
sprue, and celiac disease. It is due to a
sensitivity to gluten, which is found in wheat,
grains, and many cereals. Biopsy shows marked
atrophy, total loss, or fl attening of the villi of
the small bowel.
Answer A is incorrect. Abetalipoproteinemia is
an autosomal recessive disease that causes a defect
in the synthesis and export of lipids by mucosal
cells because of the inability to synthesize
apolipoprotein B. These patients usually have
acanthocytes (or spur cells, RBCs that have
spiny projections) and do not have any characteristic
features of the intestine found in celiac
disease.
Answer C is incorrect. Lactase defi ciency
causes osmotic diarrhea from the inability to
break down lactose into glucose and galactose.
Answer D is incorrect. Viral enteritis, usually
caused by a rotavirus, is common in children
and can cause diarrhea. However, the clinical
time course, suggested gluten sensitivity, and
fi ndings on biopsy make viral enteritis unlikely.
Answer E is incorrect. Whipple’s disease usually
presents in middle-aged men who have
malabsorptive diarrhea, and the hallmark is the
presence of periodic acid-Schiff-positive macrophages
in the intestinal mucosa. Rod-shaped
bacilli of the causal agent, Tropheryma whippelii,
are found on electron microscopy.

The correct answer is E. Wiskott-Aldrich syndrome
is an X-linked defect associated with elevated
IgA levels, elevated IgE levels, normal
IgG levels, and low IgM levels. It involves a defect
in the body’s ability to mount an IgM response
to bacteria. Recurrent pyogenic infections,
eczema, and thrombocytopenia are the
typical triad of symptoms. It does not present
with any specifi c enzyme abnormality.
Answer A is incorrect. Bruton’s agammaglobulinemia
is an X-linked defi cit and therefore
presents in males. It is a defect in a tyrosine kinase
associated with low levels of all classes of
immunoglobulins. After 6 months of age, when
the levels of maternal antibodies have declined,
patients with the disease tend to present
with recurrent bacterial infections.
Answer B is incorrect. Chédiak-Higashi disease
is an autosomal recessive disease that presents
with recurrent streptococcal and staphylococcal
infections. A defect in lysosomal
emptying of phagocytic cells due to microtubular
dysfunction is the underlying cause of
the disease.
Answer C is incorrect. Job’s syndrome involves
the failure of helper T lymphocytes to produce
IFN-γ. Since IFN-γ is a potent activator of
phagocytic cells, a decrease in its production
leads to a failure of neutrophils to respond to
chemotactic stimuli.
Answer D is incorrect. The third and fourth
pharyngeal pouches, and thus the thymus and
parathyroid glands, fail to develop in patients
with thymic aplasia (DiGeorge’s syndrome).
The disease often presents with congenital defects
such as cardiac abnormalities, cleft palate,
and abnormal facies. Thymic aplasia can also
present with tetany due to hypocalcemia.

The correct answer is D. This statement supports
the notion that there is a higher occurrence
of systemic lupus erythematosus (SLE)
among women than among men. SLE is a type
III hypersensitivity disease. Autoantibodies bind
to self-antigens to form immune complexes
that activate complement, leading to the activation
of neutrophils. Since estrogen plays an
inhibitory role on the process of clearing immune
complexes, women have a higher risk
than men of developing pathologically high
levels of immune complexes, a number of
which can lead to autoimmune diseases such
as SLE.
Answer A is incorrect. If this statement were
true, then men, who have higher levels of androgens
than women, would be at an increased
risk of developing pathologically high levels of
immune complexes (see the explanation of the
correct answer). Note that androgens actually
accelerate the clearance of circulating immune
complexes.
Answer B is incorrect. This statement does not
support the epidemiologic phenomenon that
women have a higher occurrence of SLE than
men.
Answer C is incorrect. This statement does
not support the higher occurrence of SLE in
women than in men. As stated in the explanation
of the correct answer choice, antibodies
(particularly certain antibodies against self-antigens)
are needed to form immune complexes.
Estrogen actually stimulates the process of antibody
production by B cells, which contributes
to the higher risk of developing SLE
among women than among men.
Answer E is incorrect. This statement is the
exact opposite of the correct answer choice.

The correct answer is C. Goodpasture’s syndrome
is characterized by autoantibodies forming
against the glomerular basement membrane.
Forming against a tissue, as opposed to
something in the blood, constitutes a type II
sensitivity reaction. This produces linear immunofl
uorescent staining. Renal involvement
in Goodpasture’s syndrome leads to hematuria,
anemia, and crescentic glomerulonephritis.
Along with the kidney, this syndrome may include
pulmonary involvement, leading to hemoptysis.
Answer A is incorrect. Acute poststreptococcal
glomerulonephritis occurs 1–4 weeks after a β-
hemolytic streptococci infection; it is classifi ed
as a type III sensitivity reaction in which deposits
of IgG, IgM, and C3 form in the mesangium
along the basement membrane. On immunofl
uorescent staining, a granular pattern is
seen, rather than a linear one.
Answer B is incorrect. Alport’s syndrome is not
an immune reaction against the glomerular
basement membrane. It is an X-linked disorder
characterized by absent or mutated collagen
IV, affecting kidney, nerve, and ocular function.
Answer D is incorrect. IgA nephropathy, also
known as Berger’s disease, produces mesangial
deposits of IgA antibodies. It does not produce
a linear pattern, and the staining will require
anti-IgA antibodies rather than IgG.
Answer E is incorrect. Membranous glomerulonephritis
is an immune-mediated kidney disease
that leads to sub-epithelial deposits of IgG
and complement. With immunofl uorescent
staining, it produces a granular pattern along
the glomerular basement membrane.

The correct answer is A. Selective immunoglobulin
defi ciency is a defi cit in a specifi c
class of immunoglobulins. IgA defi ciency is the
most common of these diseases. Since IgA is
the most prominent immunoglobulin found in
mucous membranes, patients suffering from a
defi ciency of it can present with sinus and lung
infections.
Answer B is incorrect. A low IgM level with
an elevated IgA level and a normal IgG level is
characteristic of Wiskott-Aldrich syndrome.
Wiskott-Aldrich syndrome involves a defect in
the body’s ability to mount an IgM response to
encapsulated bacteria. The triad of symptoms
consists of recurrent pyogenic infections, eczema,
and thrombocytopenia.
Answer C is incorrect. Normal immunoglobulin
levels and a negative nitroblue tetrazolium
dye reduction test indicate a diagnosis of
chronic granulomatous disease. Chronic granulomatous
disease involves a defect in the
phagocytic ability of neutrophils and does not
present with low levels of immunoglobulins.
The defi nitive test for this disorder is a negative
nitroblue tetrazolium dye reduction test.
Answer D is incorrect. A very high IgE level
and normal levels of all immunoglobulins are
characteristics of Job syndrome. Job syndrome
is a disorder of the immune system that involves
the failure of helper T lymphocytes to
produce INF-γ. It presents with multiple
“cold,” or non-infl amed, skin lesions and high
IgE levels.
Answer E is incorrect. Normal immunoglobulin
levels can be seen in thymic aplasia (Di-
George’s syndrome). Thymic aplasia presents
with recurrent viral and fungal infections. It results
from a congenital problem with the migration
of the pharyngeal pouches that form
the thymus and parathyroid glands. It results in
a total lack of T lymphocytes and tetany due to
hypocalcemia. It often presents with disorders
of the great vessels and heart.

The correct answer is B. Microscopic polyangiitis
is one of the trio of diseases (with Wegener’s
granulomatosis and Churg-Strauss syndrome)
that are referred to as the ANCA
(antineutrophil cytoplasmic antibody)-associated
vasculitides. Over 80% of patients with
this disease have ANCA, usually the perinuclear
pattern of staining (P-ANCA) type. Infl ammation of the pulmonary capillaries,
which can lead to hemoptysis, is common in
these patients, and 90% of patients have necrotizing
glomerulonephritis (leading to hematuria).
Other common symptoms include intestinal
pain/bleeding, muscle pain, and weakness.
The pathologic lesions are similar to those
found in classic polyarteritis nodosa (PAN), but
unlike PAN, large and muscular arteries as well
as those in the pulmonary circulation are
spared. The term “classic” is now often added
to the term PAN to differentiate classic polyarteritis
nodosa from other small-vessel vasculitides
(such as microscopic polyangiitis), which
are now thought to represent distinct entities.
Classic polyarteritis nodosa has little association
with ANCA.
Answer A is incorrect. Anticentromere antibodies,
which are found in 90% of patients
with the CREST variant of scleroderma, are
not particularly associated with microscopic
polyangiitis. Anticentromere antibodies are
more specifi c for the CREST variant of scleroderma.
Answer C is incorrect. Anti-Smith antibodies
are found in 20%–30% of patients with systemic
lupus erythematosus and are not particularly
associated with microscopic polyangiitis.
“Smith antigen” describes certain core proteins
of small nuclear ribonucleoprotein particles.
Nonspecifi c antinuclear antibodies and/or
rheumatoid factor may be found in patients
with microscopic polyangiitis, but anti-Smith
antibodies are more specifi c for systemic lupus
erythematosus.
Answer D is incorrect. Anti-ribonucleoprotein
(anti-RNP) antibody SS-A (Ro), which is present
in 70%–95% of patients with Sjögren’s syndrome,
is not particularly associated with microscopic
polyangiitis. Anti-RNP SS-A is more
specifi c for Sjögren’s syndrome.
Answer E is incorrect. Anti-ribonucleoprotein
(anti-RNP) antibody SS-B (La), which is present
in 60%–90% of patients with Sjögren’s syndrome,
is not particularly associated with microscopic
polyangiitis. Anti-RNP SS-B is more
specifi c for Sjögren’s syndrome.

The correct answer is D. The infant’s family
history is suggestive of a trait with X-linked inheritance,
and the preponderance of bacterial
infections suggests a defect in the humoral (antibody-
mediated) immune response. These two
clues are most suggestive of a diagnosis of Bruton’s
X-linked agammaglobulinemia. The molecular
defect occurs in a signaling molecule
named Btk (Bruton’s tyrosine kinase), leading
to maturing arrest of developing B cells at the
pre-B-cell stage. Arrest at the pre-B-cell stage
would result in an inability to produce immunoglobulins,
and thus the patient would have
very low levels of all immunoglobulins in his
serum. Indeed, it should be noted that these
patients are particularly susceptible to extracellular
pyogenic bacterial infections with organisms
such as Haemophilus infl uenzae, Streptococcus
pyogenes, Staphylococcus aureus, and
Streptococcus pneumoniae.
Answer A is incorrect. Absence of T lymphocytes
would result in a defect in cell-mediated
immunity, and the patient would be more
highly susceptible to viral and intracellular
bacterial pathogens.
Answer B is incorrect. A CD4+ T-lymphocyte
count not an inherited genetic defect, and one that
results in a defect in cell-mediated immunity.
Answer C is incorrect. The physical examination
and family and patient history are all
highly suggestive of an immunoglobulin defi -
ciency.
Answer E is incorrect. Low serum IgA levels
are suggestive of selective IgA defi ciency, the
most common inherited immunodefi ciency in
the European population and, interestingly
enough, one that appears to have no striking
disease associations.

The correct answer is F. The contact dermatitis
that erupts following re-exposure to a poison
ivy plant is a type IV hypersensitivity reaction,
also known as delayed-type hypersensitivity.
This reaction can only occur if an individual
has had a prior exposure to the antigen, which
triggers the differentiation of CD4+ T lymphocytes
into T-helper type 1 lymphocytes. When
these differentiated cells are reexposed to that
antigen, they are quickly activated to secrete
cytokines, which mediate the local infl ammatory
response that takes place in the skin.
Answer A is incorrect. Goodpasture’s syndrome
is a type II hypersensitivity reaction and
usually affects the lungs and kidneys.
Answer B is incorrect. Histamine is one of the
primary mediators released, together with leukotriene
and prostaglandin, during a type I hypersensitivity
reaction.
Answer C is incorrect. Type IV hypersensitivity
reactions are mediated by previously sensitized
T lymphocytes, not B lymphocytes.
Answer D is incorrect. The patient must have
been previously exposed in order to activate
the cytokines to mediate the dermatitis.
Answer E is incorrect. Contact dermatitis is a
type IV hypersensitivity reaction, not a type I
hypersensitivity reaction.

The correct answer is A. Ataxia-telangiectasia
involves a defect in DNA repair enzymes. The
image shows spider angiomas, which are a
common symptom in patients with this condition.
Ataxia-telangiectasia is associated with an
IgA defi ciency and cerebellar problems leading
to ataxia and, in this case, multiple falls.
Answer B is incorrect. Granulomas are collections
of cells seen in (among other things)
chronic granulomatous disease. This disease is
caused by an inability of neutrophils to kill
bacteria once they have phagocytosed them.
Answer C is incorrect. Bruton’s agammaglobulinemia
is an X-linked defi cit and therefore
presents in males. It is a defect in a tyrosine kinase
associated with low levels of all classes of
immunoglobulins. After 6 months of age, when
the levels of maternal antibodies have declined,
patients with the disease tend to present
with recurrent bacterial infections. Patients
also presents with uniformly low antibody titers
of all classes.
Answer D is incorrect. The third and fourth
pharyngeal pouches, and thus the thymus and
parathyroid glands, fail to develop in patients
with thymic aplasia (DiGeorge’s syndrome).
The disease often presents with many congenital
defects such as, cardiac abnormalities, cleft
palate, and abnormal facies. Thymic aplasia
can also present with tetany due to hypocalcemia.
Answer E is incorrect. Visual hallucinations
are not a symptom of any of the known immune
defi ciencies.

The correct answer is C. Multiple sclerosis is
a central nervous system (CNS) demyelinating
disorder characterized by lesions that are separated
by both time and anatomic location in
the CNS. The exact etiology is unknown, but
there is evidence supporting a role of autoimmune
antibody attack to the CNS myelinsecreting
oligodendrocytes. Oligodendrocytes,
which are found in the CNS, are involved in
myelination of axons.
Answer A is incorrect. Astrocytes are found in
the central nervous system and are involved in
regulating the metabolic and structural environment
of neurons, including repair and scar
formation. Astrocytes are not the primary cells
affected in multiple sclerosis, but they may proliferate
in areas of multiple sclerosis lesions in
an effort to repair infl ammatory damage.
Answer B is incorrect. Ependymal cells line the
ventricles. Disruptions in this cell barrier can
cause proliferation of astrocytes nearby, but is
not thought to be related to multiple sclerosis.
Answer D is incorrect. Schwann cells are
found in the peripheral nervous system and are
involved in myelination of axons. Schwann
cells are not the primary cells affected in multiple
sclerosis. The morphologic changes in
this disease are limited to the central nervous
system.
Answer E is incorrect. T cells are the primary
cells responsible for cellular immunity. It is
likely that they are involved in the putative autoimmune
attack on the central nervous system
in multiple sclerosis, but they are not the cells
primarily damaged in this disease.

The correct answer is E. JRA may appear with
a different presentation than adult-onset RA.
By defi nition, JRA begins before age 16 years
and must include arthritis in at least one joint
for at least 6 weeks. Additionally, the morphologic
joint pathology is similar to that of adultonset
RA. However, there are several signs and
symptoms that occur more commonly in JRA
than in adult-onset RA; these include increased
likelihood of systemic onset (with symptoms
including high fevers, lymphadenopathy, and
hepatomegaly), increased likelihood of large
joint involvement, and increased likelihood of
antinuclear antibody seropositivity. Furthermore,
JRA patients are less likely to have rheumatoid
nodules and rheumatoid factor.
Answer A is incorrect. There are several signs
and symptoms that occur more commonly in
JRA than in adult-onset RA, including increased
likelihood of systemic onset, increased likelihood
of large joint involvement, and increased
likelihood of antinuclear antibody seropositivity.
Answer B is incorrect. Systemic symptoms are
more likely, but high levels of serum rheumatoid
factor are less likely, in patients with JRA.
Answer C is incorrect. Both systemic symptoms
and large joint involvement are more
likely in patients with JRA.
Answer D is incorrect. Systemic symptoms are
more likely, but high levels of serum rheumatoid
factor are less likely, in patients with JRA.

The correct answer is B. CD2 is a marker
present in all lymphocytes of thymic origin,
and is in the Ig superfamily of adhesion molecules.
In T lymphocytes, it precedes either
CD4 or CD8 expression and is present
throughout the cell’s life. It is also expressed by
natural killer cells.
Answer A is incorrect. B7 is a protein complex
consisting of CD80 and CD86 glycoproteins
that is present on antigen presenting cells, including
B lymphocytes. CD80/86 serves as a ligand
for the costimulatory receptor CD28 present
on T lymphocytes; a dual CD28-TCR
signal is a potent activator of T lymphocytes.
Answer C is incorrect. CD3 is a pan-T-lymphocyte
marker that complexes with T-cell receptor
and CD4 or CD8 to convey activation
signals to the T lymphocytes. CD3 is not present
on natural killer cells.
Answer D is incorrect. CD4 is present on the
surfaces of helper (rather than cytotoxic) T
lymphocytes, while CD8 is present on the surfaces
of cytotoxic (rather than helper) T lymphocytes.
Answer E is incorrect. CD19 is present on B
lymphocytes, CD8 is present on cytotoxic
T lymphocytes, and CD4 is present on helper
T lymphocytes.
Answer F is incorrect. T-cell receptor (TCR)
is an α/β heterodimer encoded by genes undergoing
V(D)J recombination. Each clone of
T lymphocytes therefore binds a wide range of
antigens owing to the specifi city of this receptor.
Natural killer cells do not express TCR.