Professional Documents
Culture Documents
therapy and
inflammation
MCQs
101
Lymphocytes:
C. Secrete cytokines.
D. Contain CD3 cell markers.
Human T cells are composed of helper, cytotoxic, and suppressor cells. They have
distinct cell surface receptors that enable them to recognize processed antigens on the
surface of antigen-presenting cells in association with major histocompatibility complex
(MHC) molecules. They secrete numerous cytokines which are involved in cell–cell
communication. CD3 is a pan-T-cell marker and is part of the T-cell receptor complex. T
cells contain receptors for immunoglobulins that enable them to induce immune
responses to foreign antigens.
A. Integrins.
B. Immunoglobulin superfamily.
C. Cadherins.
D. Selectins.
A great deal of information has been obtained in recent years regarding mechanisms of
leukocyte homing and migration in acute inflammation. Much of our understanding of
these processes stems from work on cellular adhesion molecules involved in cell–cell and
cell–matrix interactions. There are currently four families of cell adhesion molecules that
have been classified: cadherins, immunoglobulin superfamily, selectins, and integrins.
During acute inflammation, endothelial cells are induced to express P-selectin.
Neutrophils attach to P-selectin at sites of inflammation and are caused to roll along the
vascular endothelium. Later expression of E-selectin by vascular endothelium contributes
to this process. Full adhesion and extravasation of neutrophils at vascular endothelium
requires the expression of a VLA-4 integrin by leukocytes that binds to ICAM-1 (an
immunoglobulin superfamily member) on endothelial cells. VLA-4 is expressed by
leukocytes, not by endothelial cells.
3. Which form of steroid is generally most potent?
A. Cream.
B. Lotion.
C. Ointment.
D. Foam.
E. Gel.
The ointment form of a topical corticosteroid is generally more potent than other forms of
the same drug. This is largely related to the occlusive effects of ointments, which tend to
prevent water evaporation from the skin surface and enhance drug absorption.
4. The classic complement cascade is initiated primarily by which ONE of the following
molecules?
A. Oligosaccharides.
B. Antibody-antigen complexes.
D. Nucleic acids.
E. Radiographic contrast medium.
The classic complement cascade is activated by many factors, including IgG, IgM,
antigen-antibody complexes, proteolytic enzymes, C-reactive protein, and RNA viruses.
In contrast, the alternative complement cascade is activated by bacterial cell walls,
endotoxic polysaccharides, aggregated immunoglobulins, and radiographic contrast
medium
5. Tincture
A. Oil-in-water
B. Water-in-oil
C. Alcohol-based
D. Propylene glycol-based
E. Powder in ointment
6. Lotion
A. Oil-in-water
B. Water-in-oil
C. Alcohol-based
D. Propylene glycol-based
E. Powder in ointment
7. Cream
A. Oil-in-water
B. Water-in-oil
C. Alcohol-based
D. Propylene glycol-based
E. Powder in ointment
8. Paste
A. Oil-in-water
B. Water-in-oil
C. Alcohol-based
D. Propylene glycol-based
E. Powder in ointment
A. Oil-in-water
B. Water-in-oil
C. Alcohol-based
D. Propylene glycol-based
E. Powder in ointment
Ointments are generally considered water-in-oil formulations, whereas creams and lotions
are oil-in-water formulations. Solutions and tinctures are alcohol-based with solutions
containing variable amounts of propylene glycol. Gels are propylene glycol-based agents.
Pastes are creams or ointments to which powder has been added.
10. All of the following are true regarding natural killer (NK) cells EXCEPT:
Natural killer cells are CD16-positive cells capable of natural killer (NK) and antibody-
dependent cell cytotoxicity (ADCC). They are important cells in host defense against viral
infections and tumors. They constitute 20% of peripheral blood lymphocytes; however,
they lack T-cell and B-cell markers.
11. In acute inflammation, leukocytes are induced to roll on vascular endothelium by
increased endothelial cell expression of all of the following EXCEPT:
A. P-selectin.
B. E-selectin.
A great deal of information has been obtained in recent years regarding mechanisms of
leukocyte homing and migration in acute inflammation. Much of our understanding of
these processes stems from work on cellular adhesion molecules involved in cell–cell and
cell–matrix interactions. There are currently four families of cell adhesion molecules that
have been classified: cadherins, immunoglobulin superfamily, selectins, and integrins.
During acute inflammation, endothelial cells are induced to express P-selectin.
Neutrophils attach to P-selectin at sites of inflammation and are caused to roll along the
vascular endothelium. Later expression of E-selectin by vascular endothelium contributes
to this process. Full adhesion and extravasation of neutrophils at vascular endothelium
requires the expression of a VLA-4 integrin by leukocytes that binds to ICAM-1 (an
immunoglobulin superfamily member) on endothelial cells. VLA-4 is expressed by
leukocytes, not by endothelial cells.
lntegrins are adhesion receptors on cells that mediate cell–cell and cell–matrix
interactions. They possess distinct ligand specificity. lntegrin receptor families are
classified according to their eight subunits. A multitude of integrins may be expressed by
leukocytes or fibroblasts and show specificity for binding to collagens, laminin, and
fibronectin. Most cells express several integrins and can therefore bind to several
extracellular matrix proteins.
13. Lipophilic topical steroid agents are generally more effective than hydrophilic agents
because of all of the following EXCEPT:
In stratified squamous epithelium, the major barrier to drug absorption is the stratum
corneum. There is no active transport across the stratum corneum; therefore, drug
transport across this skin layer is dependent on Fick law of diffusion.
15. All of the following substances have been shown to mediate pruritus EXCEPT:
A. Histamine.
B. Interleukins.
C. Opioids.
D. Temperature.
E. Substance P.
Histamine, opioids, thermal stimuli, and substance P have all been demonstrated to
mediate pruritus either by direct effects on itch receptors or through effects on mast cells.
While interleukins are known products of keratinocytes and are mediators of the
inflammatory response, they have not been demonstrated to induce pruritus.
16. Characteristics of ointments include all EXCEPT:
A. Lipophilic preparations.
Ointments are lipophilic preparations that, if pre pared as an emulsion, are usually water-
in-oil mixtures. They are often composed of a petrolatum base containing a complex
mixture of various hydrocarbons, including microcrystalline hydrocarbons. Because of the
hydrophobic nature of ointments, they tend to repel, not absorb, water unless an
emulsifying agent is present to form an absorption base.
17. Topical steroids can be used for all of the following EXCEPT:
A. Inflammatory lesions.
B. Hyperplastic lesions.
C. Infiltrative lesions.
D. Infectious lesions.
E. Pruritic lesions.
18. Adverse effects of long-term use of superpotent topical steroids include which of the
following?
A. Epidermal atrophy.
B. Striae.
C. Rosacea.
Superpotent topical steroids, when used daily for as short as several weeks (depending
on the surface area, site, and patient age), may have serious and lasting side effects.
Among the more commonly encountered side effects are steroid-induced rosacea,
epidermal atrophy, and subsequent striae. Rarely is suppression of the hypothalamic-
pituitary-adrenal axis seen with topical steroid treatment, although this may occur,
especially in children and infants.
19. The effect of a particular topical agent on a specific cutaneous disorder depends on
what?
The effect of any topically applied agent depends on drug availability from the vehicle in
which it is prepared, penetration of the agent through the skin, interactions of the agent
with various cellular receptors, and its degradation in the skin.
20. In order to combine two immiscible liquids it is necessary to do all of the following
EXCEPT:
C. Reduce the surface tension at the interface between the two agents.
D. Have an excess of the hydrophobic agent.
Emulsions are composed of two immiscible liquids—usually oil and water. When forming
a vehicle for a particular topical therapeutic agent oftentimes a water-in-oil or oil-in-water
emulsion is used. The internal phase is said to be dispersed in the external or continuous
phase. This can only occur with the use of a surfactant (detergent) to reduce surface
tension at the interface of the two phases. Whether the emulsion is oil-in-water or water-
in-oil is determined by the amount of oil and water in the compound and the surfactant
used. Most creams are oil-in-water-based. It is not necessary to have excess of either the
hydrophilic or hydrophobic phase in order to form an emulsion.
21. All of the following regarding intralesional steroid therapy are true EXCEPT:
22. All of the following statements are true regarding human T cells EXCEPT:
Increased skin temperature, wetting the skin, and occlusive therapy all contribute to
increased permeability of the stratum corneum to topical medications. Stripping the skin
of the stratum corneum increases penetration by topical steroids through elimination of
the largest barrier to skin absorption.
Questions 24 - 28 of 75
For each numbered item, choose the most likely associated lettered item. Each
numbered item has ONLY ONE correct answer. Within each group, each lettered
item may be the answer to one, more than one, or none of the numbered items.
24. Cholestasis-related
26. Dermographism
Multiple therapies have been tried for cholestasis pruritus. Although there is no correlation
between the levels of serum conjugated bile acids and pruritus, substantial relief has
been obtained with bile acid-sequestering agents, e.g., cholestyramine. Uremic pruritus
appears to be best controlled by ultraviolet B (UVB) therapy. There is no correlation
between level of uremia or serum creatinine and pruritus; furthermore, dialysis has not
been shown to substantially reduce pruritus in these patients. Dermatographism involves
an accentuated wheal and flare response to stroking the skin. It is primarily histamine-
mediated and is therefore responsive to antihistamine therapy. Prurigo nodularis and
lichen simplex chronicus are both types of neurodermatitides. Often times, these
disorders are associated with habitual rubbing at times of stress. The pruritus here is
often severe. Once systemic causes for the pruritus have been ruled out, successful
treatment of these lesions usually requires potent topical or intralesional steroids. A
consideration of mild systemic anxiolytic therapy or improved stress management
techniques might also be useful in this situation.
29. Drug absorption across the stratum corneum is calculated using which law?
A. Murphy.
B. Fitzpatrick.
C. Fick.
D. Koebner.
E. Mother-in-law.
Because there is no active transport across the stratum corneum, transport across it is
dependent on passive diffusion, or Fick law. In Fick law, J = flux, or flow of diffusing drug,
K = partition coefficient between the stratum corneum and the vehicle; D = diffusion
coefficient of the stratum corneum; ΔC = concentration gradient between the skin surface
and the epidermis, and d = the thickness of the stratum corneum.
30. Dermal effects of long-term topical steroid use include which of the following?
D. Inhibition of melanogenesis.
E. Vasoconstriction.
Dermal effects of long-term topical steroid use include decreased collagen synthesis with
reduction in ground substance, which leads to decreased vascular support and
subsequent striae. Although immediate effects of topical steroids include
vasoconstriction, long-term use promotes vasodilation, often as a rebound phenomenon.
Inhibition of melanocyte function is an effect of topical steroid use on the epidermis.
31. Cytokines synthesized and expressed in skin include which of the following?
A. GM-CSF.
B. TNF-α.
C. TGF-β.
D. IL-1.
E. Choices A, B, and D.
F. All of the above.
32. The rate of topical drug absorption depends on which of the following?
The rate of topical drug absorption is related to Fick law as previously described. The rate
of absorption depends on the concentration gradient from the stratum corneum to the
dermal vasculature. Initially, the absorption of a topically applied agent as the drug moves
from the vehicle to the stratum corneum through the epidermis to the dermal vessels is
slow. This initial phase of absorption is the lag phase. Once the amount of drug
absorption per unit of time is constant, we have reached the steady-state phase of
absorption. The vehicle used is also important for drug absorption, more water-
impermeable (i.e., hydrophobic) vehicles allowing more absorption of drug through a
hydrated stratum corneum. In addition, the vehicle used is important in determining the
partition coefficient of a particular drug as relates to Fick law.
Choose the ONE BEST answer to each of the following questions:
33. The average amount of ointment required to cover an entire adult skin surface is
which of the following?
A. 1 gram.
B. 10 grams.
C. 45 grams.
D. 75 grams.
E. 100 grams.
The average adult individual requires 30 to 60 grams of ointment to cover the entire
cutaneous surface area.
D. It never occurs.
E. It is rarely reversible.
Tachyphylaxis may begin within one week of initiating treatment with a potent topical
steroid. The ability to fully respond to the same medication usually returns within a week
of stopping the topical therapy. It is therefore best to treat disorders with potent agents
over a short period of time with "rest" periods, either without steroid treatment or with use
of a substantially weaker steroid.
35. Which one of the following is true regarding cytokines?
36. The free nerve endings that serve as the point of initiation of itch sensation are:
The free nerve endings that serve as points of initiation of itch sensation are located
primarily in the upper dermis. They form a subepidermal nerve network. These free nerve
endings are terminals of unmyelinated cutaneous nerves that are composed mainly of
type C fibers. Free nerve endings that project into the epidermis reach the granular layer
and then spread laterally.
A. PGE2, PGD2, and PG12 are potent proinflammatory agents in the skin.
B. They are formed by cyclooxygenase conversion of arachidonic acid.
PGE2, PGD2, and PG12 are highly potent proinflammatory agents in skin, causing
erythema, edema, and pain in nanomolar concentrations. NSAIDS inhibit formation of
prostaglandins by direct inhibition of cyclooxygenase and, therefore, conversion of
arachidonic acid to prostaglandins. Increased levels of prostaglandins in skin are seen in
response to UV irradiation, in allergic contact dermatitis, and in the physical urticarias.
Questions 38 - 42 of 75
For the following questions the set of lettered headings accompanies a list of
numbered words or phrases. For each numbered word or phrase, choose:
A. If the item is associated with A only
B. If the item is associated with B only
C. If the item is associated with both A and B
D. If the item is associated with neither A nor B
A. IgG
B. IgM
C. Both
D. Neither
A. IgG
B. IgM
C. Both
D. Neither
A. IgG
B. IgM
C. Both
D. Neither
A. IgG
B. IgM
C. Both
D. Neither
A. IgG
B. IgM
C. Both
D. Neither
43. Human cutaneous mast cells release histamine in response to which of the following?
A. C3a.
B. CSa.
C. IgE.
D. Substance P.
Human mast cells release histamine in response to numerous stimuli. Mast cells possess
receptors for the Fc portion of IgE and for the anaphylatoxins C3a, C4a, and C5a.
Additionally, numerous hormones and endogenous opiate peptides can cause mast cell
degranulation. Known mast cell activators include IgE, C3.a, C5a, opiates, and substance
P.
Because of the superpotent nature of class 1 steroids, their use should generally be
limited to 2 weeks of continuous therapy with a subsequent rest period to reduce the
likelihood of side effects and tachyphylaxis of the agent used. Generally, a 1- to 2-week
rest period is sufficient to avoid severe side effects of the stronger topical steroid
therapies. Retreatment with more potent topical steroids should then be initiated for
exacerbation of the disease process being treated.
45. Traditional methods for determining topical steroid potency include which of the
following?
A Thermal measurements.
B. Epidermal thickness changes.
C. Vasodilator assay.
D. Vasoconstrictor assay.
In 1962, the vasoconstrictor assay was presented as a novel method for determining
percutaneous absorption of topical steroids. Since that time, the assay has undergone
some modifications but has essentially remained the "gold standard" for determining
topical steroid potency.
For each of the following numbered items, choose the most likely associated
lettered. Each numbered item has ONLY ONE correct answer. Within each group,
each lettered item may be the answer to one, more than one, or none of the
numbered items.
A. PGE2.
B. PGD2.
C. PG12.
D. LTB4.
E. 5-HPETE.
The main cyclooxygenase product of human skin mast cells is PGD2, which along with
histamine is responsible for much of the inflammatory response of mast cells. PGE2 and
PG12 are found in skin but at lower concentrations than PGD2. LTB4 and 5-HPETE are
products of the lipoxygenase pathway in human skin.
52. Long-term topical steroid use that results in subsequent decreased efficacy over time
is termed what?
A. Anaphylaxis.
B. Tachyphylaxis.
C. Habituation.
D. Tachydermia.
E. Koebnerization.
A. HLA-DR.
B. OKT6.
C. Vimentin.
D. S-100.
Langerhans cells are responsible for suprabasal antigen presentation in skin. They
contain numerous phenotypic markers, including HLA-DR, CDla, HLA- DS, OKT6,
vimentin, S-100, Fc receptors, and C3 receptors. These cells are mesenchymal and are
derived from bone marrow precursor cells.
For the following questions the set of lettered headings accompanies a list of
numbered words or phrases. For each numbered word or phrase, choose:
Mast cells contain preformed and newly formed mediators that are released during
degranulation and subsequent activation. Preformed mediators contained within mast cell
granules include histamine, heparin, trypsin, chymotrypsin, and arylsulfatases.
Arachidonic acid metabolites, including the prostaglandins, thromboxanes, and
leukotrienes, are synthesized following mast cell activation. Both histamine and PGD2
cause increased vascular permeability and smooth muscle contraction. Neither histamine
nor PGD2 are involved in promoting platelet aggregation. PGD2 is an inhibitor of platelet
aggregation. Platelet-aggregating factor, an additional mast cell product, is responsible
for mast cell-induced platelet aggregation.
58. Substance P has which of the following properties?
60. Growth factor for activated T cells, induces factor (TNF) lymphocyte-activated
killer (LAK) cells
Interleukin-1 (IL-1) is a cytokine produced constitutively by the epidermis. There are two
forms of IL-1, alpha and beta. Both forms bind to the same receptor; however, the
bioactive form in skin is IL-1α. Elevated levels of IL-1 are associated with fevers following
increased UV exposure of skin.
Water in the stratum corneum may be "bound' or "free." As the stratum corneum becomes
hydrated, more free water is available, allowing water molecules to move more freely
through the skin. This increased water content of the stratum corneum gives it a larger
diffusion constant in Fick law as a result of increased movement of molecules across a
fixed concentration gradient.
66. In order for corticosteroids to exert their physiologic effects, they must bind to what?
E. Mitochondria.
Corticosteroids exert their effects by diffusing through cell membranes, binding to specific
cytosolic receptors, and subsequently migrating to the cell nucleus, where the steroid-
receptor complex binds to cellular DNA to initiate transcription of various effector
molecules.
67. Which of the following factors significantly and positively influence absorption of
topically applied drugs?
A. Hydrophilic molecule.
B. Increased frequency of application greater than three times per day.
There are three types of histamine receptors in the human body: H1 receptors are found
in the skin and brain; H2 receptors mediate gastric acid secretion; and H3 receptors are
found in brain, lung, and other tissue. Dermal blood vessels contain both H1 and H2
receptors, which cause vasodilation when stimulated. Itch is mediated through the H1
receptor.
69. Which ONE of the following is true regarding antigen presentation by macrophages?
Macrophages take up and internalize foreign antigens, which are then processed
internally. Macrophages then secrete IL-1, which induces T-cell recognition of the foreign
antigen only in association with la (Class II MHC) antigens. IL-2 is secreted by activated T
cells following recognition of processed antigens on macrophage cell surfaces.
70. Which one of the following is TRUE regarding pruritus?
B. Itch and pain sensations are carried to the central nervous system via the same
sensory afferents.
C. The reflex response to itch is the same as the reflex response to pain.
D. Itch cannot be elicited when the dermis and epidermis have been removed.
E. Itch and pain cannot be experienced in the same site simultaneously.
71. Changes in the structure of the basic steroid moiety (Figure 3–1) that have led to
increased potency include which of the following?
A. Biliary cirrhosis.
B. Anemia.
C. Uremia.
D. Polycythemia vera.
E. All of the above.