Inflammation & Repair Flashcards
1
Q
- A researcher is studying acute inflammation.
Specifically, he has designed an antibody that binds
to and blocks the activity of one of the Toll-like
receptors. When the antibody is used, which step in
acute inflammation would be directly blocked?
A. Identification of the inciting agent
B. Recruitment of white blood cells
C. Removal of the inciting agent
D. Regulatory steps to maintain control of the
inflammatory response
E. Resolution of the inflammation
A
- Correct: Identification of the inciting agent (A)
The five possible answers listed are the five general
steps of acute inflammation in order from start to
finish. The Toll-like receptors are important in allowing
immune cells to identify the agent that is precipitating
the acute inflammation (A). For (B-E), see
previous discussion.
2
Q
- The hospital laboratory receives a specimen
from a clinical physician for analysis. The specimen
vial contains a watery fluid. Testing indicates a very
low concentration of protein, and only a very few red
and white blood cells are identified on microscopic
examination. Of the following disease types, which
is the most likely source of the fluid collection from
which this sample was obtained?
A. Acute appendicitis
B. Subdural hematoma
C. Bronchopneumonia
D. Congestive heart failure
E. Acute pancreatitis
F. Sepsis
A
- Correct: Congestive heart failure (D)
The fluid described is a transudate, which would produce a serous effusion in a body cavity. A serous effusion is one that is watery, clear, and light yellow in color.
Transudates are produced by either high intravascular
pressures, such as would occur with congestive heart
failure (D), or with low oncotic pressure, such as in
hypoalbuminemia. With high intravascular pressure,
fluid is essentially forced out of the vasculature into the body cavity or soft tissue, whereas with hypoalbuminemia,
the oncotic pressure of the blood, which is the
force that draws fluid back into the vasculature from
the soft tissue, is low. Hypoalbuminemia can occur in liver failure, because of decreased production of albumin,
or in nephrotic syndrome, because of loss of albumin
in the urine. The other choices would cause an
exudate, which has a high concentration of protein and
a prominent cellular component (A-C, E-F).
3
Q
- A 6-year-old boy falls off his bicycle while in
the driveway of his house. His mother witnesses
him fall and sees that he strikes his knee against the
ground but does not hit his head. She feels that he
is fine and returns to her work. About 20 minutes
later, he comes in the house to get a drink of water.
She can see that the skin on his knee where he hit
the ground is intact but red. The red discoloration of
the skin is not a bruise. Of the following mediators,
which played the largest role in producing this visible
change in the skin?
A. ICAM-1
B. PECAM-1
C. Histamine
D. Thromboxane A2
E. E-selectin
F. P-selectin
A
- Correct: Histamine (C)
Histamine plays a large role in vasodilation, and vasodilation produces the erythema (red discoloration)
and heat usually associated with acute inflammation
(C). Thromboxane A2 causes vasoconstriction (D),
and the other mediators listed (A-B, E-F) participate
in the migration of white blood cells through the wall
of the blood vessel to the site of the inflammation.
4
Q
- A researcher is studying acute inflammation
and has developed an antibody for her research. This
antibody, called ILF-2, binds to a receptor on the
endothelial cell and blocks it. Binding of the antibody
causes impairment of leukocyte rolling, though
margination still occurs. Of the following receptors,
which is ILF-2 most likely binding to?
A. E-selectin
B. L-selectin
C. ICAM-1
D. PECAM-1
E. Integrin
F. Sialyl-Lewis-X
A
- Correct: E-selectin (A)
L-selectin and Sialyl-Lewis-X are found on the leukocytes
(B, F). Integrins (on leukocytes) and ICAM-1 (on endothelial cells) participate in tight adhesion of the white blood cell to the vessel wall (C, E), and PECAM-1 participates in transmigration of the white blood cell through the wall of the vessel (D). E-selectin is found on endothelial cells and participates in leukocyte rolling and adhesion (A).
5
Q
- A medical student is writing a paper on opsonins.
In the paper, the student lists the various opsonins and
the appropriate receptor that they bind to. In reading
the paper, the student’s professor identifies one
mispairing. Of the following pairings, which represents
an opsonin and the wrong receptor for that opsonin?
A. Integrin and ICAM-1
B. IgG and the Fc Receptor
C. CD34 and L-selectin
D. C1q and collectins
E. Complement receptors (1 and 3) and C9
A
- Correct: Complement receptors (1 and 3) and
C9 (E)
Opsonin is a general term for a group of molecules
that bind to bacteria and dead cells and allow for their
recognition by leukocytes as something needing to be
ingested and destroyed. The opsonins are IgG, fragments
of C3, and collectins. IgG binds to the Fc receptor
(B), and collectins bind to C1q, (D) but fragments
of C3 bind to complement receptors (E). Integrin and
ICAM-1 and CD34 and L-selectin are appropriately
paired (A, C), but none of these mediators are opsonins.
6
Q
- A medical student in a laboratory is studying
the effects of a drug that irreversibly binds to and
inhibits the function of ICAM-1. When the drug
is administered, the student observes that acute
inflammation is impaired. Of the following, which
protein is also indirectly involved?
A. Sialyl-Lewis-X
B. L-selectin
C. CD11/CD18 integrins
D. VLA-4
E. CD 31
A
- Correct: CD11/CD18 integrins (C)
During the process of firm adhesion and transmigration,
CD11/CD18 on the leukocyte binds to ICAM-1 (C). Sialyl-Lewis-X binds to P-selectin and E-selectin, L-selectin binds to GlyCam-1 and CD34, VLA-4 binds to VCAM-1, and CD31 on endothelial cells binds to CD31 on white blood cells.
7
Q
- The parents of a young child bring him to a pediatric
hospital for evaluation. Their son has frequently
sustained middle ear infections and has had two episodes
of pneumonia, both requiring hospitalization.
Testing indicates that the child has a deficiency in the
β subunit of CD18. Which of the following diseases
does the child have?
A. Leukocyte adhesion deficiency type 1
B. Leukocyte adhesion deficiency type 2
C. Chronic granulomatous disease
D. Chediak-Higashi
E. Cryopyrin-associated periodic fever syndromes
A
- Correct: Leukocyte adhesion deficiency type 1
(LAD-1) (A)
LAD-1 is due to a defective production of the β subunit
of CD18 (A). LAD-2 is due to absence of sialyl-
Lewis-X (B). Chronic granulomatous disease is due to
impaired phagocyte oxidase production (C). Chediak-
Higashi syndrome is due to a mutation of CHS1, a
lysosomal trafficking regulator (D). Cryopyrin-associated
periodic fever syndromes are due to gain-of-function
mutations affecting the inflammasome (E).
8
Q
- A 56-year-old male experiences “crushing”
substernal chest pain and is taken by private vehicle
to the emergency department of the local hospital.
A troponin-I test performed in the emergency
room indicates a concentration of 0.01 ng/mL, and
a 12-lead electrocardiogram (ECG) shows ST elevation
in the anterior leads. Streptokinase is administered
within 20 minutes of the onset of symptoms
and the patient’s symptoms resolve. A repeat ECG
after administration of the drug is normal. Given
that some degree of acute inflammation occurred in
this process, of the following, which is the most likely
outcome in the myocardium?
A. Resolution
B. Chronic inflammation
C. Scarring
D. Prolonged pericardial effusion
E. Abscess formation
A
- Correct: Resolution (A)
Although the individual was sustaining an acute
myocardial infarct, a presumptive diagnosis was
made, and restoration of blood flow was made prior
to irreversible damage; therefore, resolution of the
inflammation is likely (A). If the troponin I had been
elevated, it would indicate irreversible damage. As
the cardiac myocytes are essentially incapable of
division, the necrotic cells would have triggered
acute inflammation; however, complete resolution is
impossible without the potential for division among
the surviving cells. In that case, scarring would be
the result (C). As the underlying etiologic cause is
neither infectious nor otherwise likely to linger in
the tissue, chronic inflammation, a prolonged effusion,
or an abscess would not occur (B, D-E).
9
Q
- A 35-year-old female is involved in a motor
vehicle accident during which she is thrown against
the steering wheel after the airbag fails to deploy,
causing her to sustain a laceration of her liver. She
is treated nonoperatively and is told at her 6 month
check-up that she has had complete resolution of the
damage to her liver. Assuming this statement is correct,
which of the following could be identified histologically
in the region of the liver where the injury
occurred?
A. Extensive fibrosis
B. Wavy fibrosis between hepatocytes
C. Increased numbers of blood vessels
D. Multiple foci of neutrophils
E. Hemosiderin-laden macrophages
A
- Correct: Hemosiderin-laden macrophages (E)
As a laceration occurred, hemorrhage is expected, and
when the red blood cells break down, hemosiderin is
deposited (E). With complete resolution, all injured
cells are replaced, and inflammatory mediators,
including inflammatory cells, are no longer present
(D). During complete resolution, fibrosis would not be
deposited (A-B). Increased numbers of blood vessels
are also indicative of chronic inflammation (C).
10
Q
- A 12-year-old male with no past medical history
is brought to the emergency room by his parents
because of flu-like symptoms, including cough,
fever, and general malaise, which are associated with
the recent development of shortness of breath. During
his evaluation, an ultrasound of the chest reveals
a large pericardial effusion, which produces right
ventricular collapse during diastole. A pericardiocentesis
is performed, removing ~ 200 mL of translucent,
watery yellow fluid. Of the following, which is
the most likely source of the fluid around the heart?
A. A metastatic pediatric neoplasm
B. A parasite
C. A viral infection
D. A bacterial infection
E. A fungal infection
A
- Correct: A viral infection (C)
The effusion as described, being watery, translucent,
and yellow, is a serous effusion, which can be found
in viral infections (C). Given the clinical scenario, the
patient most likely has a viral myocarditis or viral
pericarditis, both of which are commonly due to Coxsackie virus infection. Bacteria, fungi, and parasites are more likely to produce a fibrinous or suppurative
inflammation (B, D-E), in which case the effusion
would be less watery, and cloudy, not translucent,
and a metastatic neoplasm would be more likely to
produce a fibrinous or even hemorrhagic effusion (A).
11
Q
- A 23-year-old female falls off her bike and
strikes her thigh against the sidewalk. Bruising
occurs at the site of impact, and, within minutes, the
tissue expands at this point, creating a noticeable
bulge in the skin. Of the following mediators, which
most directly and significantly played a role in these
changes?
A. Reactive oxygen species
B. Serotonin
C. Thromboxane A2
D. Prostaglandins D2
E. Leukotriene B4
A
- Correct: Prostaglandin D2 (D)
Prostaglandins D2 and E2 cause increased vasculature
permeability and vasodilation, both of which
would contribute to fluid leaving the vascular space,
entering the tissue, and producing swelling (D).
Serotonin and thromboxane A2 cause vasoconstriction,
which would impede the changes described
(B-C), and leukotriene B4 is a chemotactic agent (E),
responsible for helping recruit white blood cells to
the site of inflammation. Reactive oxygen species are
produced as a tool to destroy invading bacteria (A).
12
Q
- A 24-year-old female develops bacterial
meningitis due to Neisseria meningitidis. On her
initial presentation to the emergency room, being
brought in by her family, she is in obvious distress
and has a fever of 103°F. Laboratory testing indicates
a white blood cell count of 15,000 cells/μL. Of
the following mediators, which is least responsible
for her symptoms, physical examination, and laboratory
findings?
A. IL-1
B. IL-6
C. IL-12
D. TNF
E. CXC chemokines
A
- Correct: IL-12 (C)
The patient has bacterial meningitis, an acute process.
IL-1, IL-6, and TNF play a role in acute inflammation,
acting on endothelium to increase adhesion
molecule expression, activating white blood cells,
and promoting systemic effects such as fever, elevation
of acute phase proteins, and increasing leukocyte production. Chemokines recruit white blood
cells to the site of acute inflammation (A-B, D-E).
Therefore, in an acute bacterial meningitis, IL-1, IL-6,
TNF, and CXC chemokines would all play a role; however,
IL-12 functions mostly in chronic inflammation
and would not play a role in the acute process (C).
13
Q
- A 2-year-old boy with recurrent infections
is found to improperly synthesize NADPH oxidase,
producing a nonworking protein. Of the following,
which is most directly responsible for his susceptibility
to infections?
A. Elevated concentrations of reactive oxygen
species
B. Decreased concentrations of reactive oxygen
species
C. Elevated concentrations of activated
α1-antitrypsin
D. Decreased concentrations of activated
α1-antitrypsin
E. Elevated concentrations of C3a and C5a
F. Decreased concentrations of C3a and C5a
A
- Correct: Decreased concentrations of
reactive oxygen species (B)
NADPH oxidase helps to synthesize reactive oxygen
species, which then play a role in killing of infectious
agents (A-B). α1-antitrypsin is an enzyme that
is contained in fluids but is not activated directly by
NADPH oxidase, and it plays a role in inhibiting the
action of enzymes (C-D). C3a and C5a increase vascular
permeability and induce vasodilation as well
as play a role in recruitment of neutrophils, but they
are produced by the action of neutral proteases and
not NADPH oxidase (E-F).
14
Q
- A 17-year-old female is brought to the emergency
room by her family because she is acutely
short of breath. Despite being given oxygen and epinephrine,
her shortness of breath continues and she
requires intubation. During the intubation, the emergency
room physician notes severe laryngeal edema.
This woman has a hereditary condition and commonly
develops edema of soft tissue in various locations.
Which of the following proteins does she lack?
A. C5
B. C3
C. C3 inhibitor
D. C1 inhibitor
E. Decay-accelerating factor
A
- Correct: C1 inhibitor (D)
The patient has hereditary angioedema, which is an
inherited defect in C1 inhibitor (C), leading to edema
of soft tissue, which can involve the larynx. (A-B,
D-E) are incorrect.
15
Q
- A pathologist is examining a slide of the
appendix. In the mucosa, submucosa, and muscularis
are numerous cells with abundant cytoplasm and
multilobed nuclei, with the lobes joined by very thin
bridges. Of the following mediators, which was most
responsible for attracting these cells to this site?
A. Leukotriene B4
B. Leukotriene C4
C. Leukotriene D4
D. Leukotriene E4
E. Substance P
A
- Correct: Leukotriene B4 (A)
The cell type described is a neutrophil, which is
an acute inflammatory cell. The disease that the
patient has is acute appendicitis. Leukotriene B4 is
a chemoattractant and plays a role in attracting neutrophils to the site of acute inflammation (A). The
remainder of the mediators, including substance P,
are primarily involved in increasing vascular permeability
(B-E), so each of these mediators could play
a role in the disease process of acute appendicitis;
however, that role would not be as a chemoattractant.
16
Q
- A pathologist is examining a slide and identifies
a lesion that is a roughly circular collection of
epithelioid macrophages. There is no central necrosis.
Of the following organisms, which is the most
likely cause of this lesion?
A. Staphylococcus aureus
B. Streptococcus pneumoniae
C. Escherichia coli
D. Pseudomonas aeruginosa
E. Mycobacterium leprae
A
- Correct: Mycobacterium leprae (E)
The lesion described is a granuloma. Granulomas are
composed of epithelioid macrophages (also referred
to as epithelioid histiocytes). While multinucleated
giant cells are often found in granulomas, their presence
is not necessary for the diagnosis of a granuloma.
Granulomatous inflammation is produced by a
variety of infectious agents as well as foreign material
and other processes. Of the organisms listed, Mycobacterium leprae produces granulomatous inflammation (E), whereas the other organisms are not
associated with granulomatous inflammation (A-D).
17
Q
- A 56-year-old alcoholic male is admitted to
the hospital with a diagnosis of pneumonia. His primary
care physician orders a test that identifies an
increased speed of sedimentation of red blood cells.
Which of the following mediators is responsible for
this change?
A. C-reactive protein
B. Serum amyloid A
C. Ceruloplasmin
D. Fibrinogen
E. Creatine kinase
A
- Correct: Fibrinogen (D)
Fibrinogen is an acute phase protein; its concentration
is elevated in acute inflammatory processes,
such as pneumonia. Fibrinogen binds to red blood
cells and thus causes rouleaux, which increases
the sedimentation rate (C). The test ordered was
the erythrocyte sedimentation rate. (A-B, D-E) are
incorrect.
18
Q
- A 68-year-old male with metastatic lung cancer
is being evaluated by his oncologist. His chemotherapy
regimen was discontinued 3 months ago due to his
poor prognosis. His wife is concerned because he has
lost 25 lbs. over the past two months. At the present
time he is on no medications, and she reports his appetite
has been poor. Which of the following polypeptides
released by immune cells in response to this patient’s
cancer is most likely to cause progressive weight loss?
A. TNF-α
B. TGF-β
C. IL-8
D. IL-10
E. IL-13
A
- Correct: TNF-α (A)
TNF-α, IL-1, and IL-6 are proinflammatory cytokines
that play a critical role in malignancy-related
cachexia, and in experimental models, antagonists
of these cytokines have been shown to mitigate this
effect (A). TGF-β is an anti-inflammatory cytokine
involved in cellular repair (B). IL-8 is a chemokine that
recruits neutrophils to the site of infection or inflammation
(C). IL-10 also plays a critical role in modulating
the immune response by down-regulating the
expression of Th1 cytokines, MHC class II antigens,
and co-stimulatory molecules on macrophages and
inhibiting the production of proinflammatory cytokines
(D). In addition to its anti-inflammatory properties,
IL-13 plays an important role in immunity to
parasitic infections (E).
19
Q
- An immunologist studying the process of leukocyte
recruitment in acute inflammation wishes to
block the process of transmigration of neutrophils
across the endothelial wall. A monoclonal antibody
against which of the following adhesion molecules
would inhibit transmigration (diapedesis) without
interfering with rolling or margination?
A. P-selectin
B. E-selectin
C. Integrin
D. ICAM-1
E. PECAM-1 (CD31)
A
- Correct: PECAM-1 (CD31) (E)
PECAM-1 (E) plays a critical role in transmigration
of the leukocyte across the vessel wall (E). The selectins
form weak adhesions between leukocytes and
endothelial cells, which slows the leukocytes during
the process of rolling (A, B). Integrins (VLA-4, Mac-1,
and LFA-1) on the leukocyte surface bind to ligands
on the endothelial surface (ICAM-1, VCAM-1) after
the initial process of leukocyte rolling (C, D). These
interactions result in tight adherence of leukocytes
to the vessel wall in preparation for diapedesis into
the extravascular site of inflammation.
20
Q
- A 70-year-old male dies of an acute ischemic
stroke. During the autopsy an incidental lesion is found
in the apex of the right upper lobe of the lung. Microscopy
reveals abundant macrophages with indistinct cell
boundaries, surrounded by a rim of lymphocytes, and a
central zone of necrotic debris. Of the following, which
is the most likely cause of this patient’s lung lesion?
A. Tissue foreign bodies
B. Tuberculosis
C. Sarcoidosis
D. Crohn’s disease
E. Leprosy
A
- Correct: Tuberculosis (B)
The microscopic description is that of a granuloma
with a central area of necrosis (i.e., caseous necrosis).
Granulomatous inflammation with caseous
necrosis is the classic finding in Mycobacterium
tuberculosis infection (B). This central necrosis has a
“cheesy” appearance on gross examination, hence the
term “caseous.” All the other conditions mentioned
are associated with granulomatous inflammation,
though not usually with caseous necrosis (A, C-E).
Crohn’s disease would not affect the lung (D), and
leprosy involves the skin (E). Sarcoidosis is a granulomatous disease that most commonly involves the lung, although any other organ can also be involved.
Granulomas in sarcoidosis are most commonly non-caseating; however, caseous necrosis has been found
in patients with sarcoidosis. The fact that the lesion is
in the apex of the lung also supports tuberculosis over
sarcoidosis, as Mycobacterium tuberculosis is most
commonly associated with the upper lobes of the lung
because of the organism’s aerophilic nature.
21
Q
- A researcher is investigating an experimental
drug (F-104), which is known to cause liver failure
in mice. Which of the following microscopic findings
would suggest that F-104 acted by inducing apoptosis
rather than necrosis of the hepatic parenchymal cells?
A. Cytoplasmic blebbing
B. Hepatocyte swelling
C. Chromatin condensation
D. Abundant myelin figures
E. Numerous inflammatory cells
A
- Correct: Chromatin condensation (C)
Of the choices, chromatin condensation (C) is the
most characteristic finding in apoptotic cells. Cytoplasmic
blebbing could be seen in either apoptosis or necrosis (A). Cellular swelling, myelin figures, and abundant inflammatory cells are seen in necrosis,
not apoptosis (B, D-E).
22
Q
- In the previous experiment, which of the following
findings would support the hypothesis that
F-104-induced apoptosis via the intrinsic pathway?
A. Monoclonal antibody that blocks TNF receptor
prevents F-104-induced liver injury
B. Monoclonal antibody that blocks Fas prevents
F-104-induced liver injury
C. An experimental drug that inhibits cytochrome c
release prevents F-104-induced liver injury
D. An experimental drug that inhibits caspase 8
prevents F-104-induced liver injury
E. An experimental drug that inhibits caspase 10
prevents F-104-induced liver injury
A
- Correct: An experimental drug that inhibits
cytochrome c release prevents F-104-induced liver
injury (C).
Cytochrome c release from the mitochondria triggers
apoptosis via the intrinsic (mitochondrial) pathway.
Inhibiting this critical step in activation of the intrinsic
pathway would be expected to interfere with
F-104 if it acted via the intrinsic pathway (C). All the
other effects, if observed, would support the hypothesis
that F-104 induces apoptosis via the extrinsic
(receptor-mediated) pathway (A-B, D-E).
23
Q
- A 56-year-old male presents to an acute care
clinic with complaints of shortness of breath and fever.
He has no past history of cigarette use. His vital signs
are temperature of 101°F, pulse of 107 bpm, and blood
pressure of 131/86 mm Hg. A chest X-ray reveals fluid
in the left side of the chest and patchy consolidation
of the lower lobe of the left lung. He is admitted to the
hospital and a thoracentesis is performed. Of the following,
what is most likely a characteristic of the fluid?
A. Watery and clear
B. Few cells identified on smear
C. Low specific gravity
D. Elevated protein
E. Numerous neoplastic cells identified on smear
A
- Correct: Elevated protein (D)
Given the clinical scenario (shortness of breath and
fever associated with pulmonary consolidation),
the patient most likely has bronchopneumonia, and
the infiltrate in the pleural cavity is most likely an
empyema, which is a form of exudate (D). Exudates
are characteristically very cellular, have a high protein
and lactate dehydrogenase concentration, and
have a high specific gravity. Exudates can occur as a
result of infection (e.g., an empyema) or lymphatic
obstruction, such as due to a lymphoma. Transudates
have low cellularity, low concentration of protein,
and low specific gravity (A-C). A pleural effusion can
be malignant, such as due to primary effusion lymphoma, bronchogenic carcinoma, or metastatic disease (E); however, this diagnosis would be much less
likely without a contributing history, and the presentation
is consistent with pneumonia.
