Cells Involved in Immune Responses 2018-2020

Question 1

1. IgE binds to which subunit of FcRI?
A. Alpha
B. Beta
C. Epsilon
D. Gamma

Answer 1

1. A, Alpha, p. 233.
   FcRI is a tetrameric structure consisting of an alpha chain that binds IgE, a beta-chain signaling subunit and two gamma subunits that exist as immunoreceptor tyrosine-based activation Motif (ITAM) – containing homodimer signaling subunit

Chapter 14: Biology of Mast Cells and Their Mediators
Middleton’s Allergy Principles and Practice, 8th ed.

Question 2

2. What is the best marker of systemic mast cell activation in anaphylaxis?
A. α-tryptase
B. β−tryptase
C. Chymase
D. Plasma histamine

Answer 2

2. B Beta−tryptase, p. 237.
   The best marker of systemic mast cell activation in anaphylaxis is an acute rise in the concentration of beta-tryptase in the peripheral circulation. Alpha tryptase is released by mast cells constitutively, beta-tryptase is stored in mast cell granules and released after IgE-dependent activation. Histamine concentrations in blood peak within 5 minutes, the tryptase concentration is maximal between 15 and 120 minutes after the onset of symptoms.

Chapter 14: Biology of Mast Cells and Their Mediators
Middleton’s Allergy Principles and Practice, 8th ed.

Question 3

3. The Early Asthmatic Reaction is a decline in respiratory function within how many minutes of bronchial allergen challenge?
A. 10-20
B. 60-90
C. 90-180
D. 240

Answer 3

3. A, 10-20 minutes, p 239.
   The early asthmatic response is a rapid deterioration of pulmonary function, as indicated by a fall in forced expiratory volume in 1 second, at 10 to 20 minutes following bronchial allergen challenge.
   Chapter 14: Biology of Mast Cells and Their Mediators
   Middleton’s Allergy Principles and Practice, 8th ed.

Question 4

4. Which is an obligate mast cell growth factor?
A. G-CSF
B. GM-CSF
C. SCF
D. VEGF

Answer 4

4. C, SCF, p 228.
   Stem cell factor (SCF), or kit ligand, is an obligate mast cell growth factor that is derived from many cellular sources. Removal of SCF leads to rapid mast cell apoptosis. SCF is the ligand for kit
   encoded by the proto-oncogene c-kit.

Chapter 14: Biology of Mast Cells and Their Mediators
Middleton’s Allergy Principles and Practice, 8th ed.

Question 5

5. The arachidonic acid metabolite prostaglandin D2 (PGD2) is synthesized by which pathway?
A. Cyclooxygenase
B. IRAK
C. Lipoxygenase
D. Pyruvate

Answer 5

5. A, Cyclooxygenase, p 233.
   Newly formed metabolites of arachidonic acid are released from mast cells after IgE-dependent activation. The cyclooxygenase pathway produces PGD2, whereas the lipoxygenase
   pathway forms Leukotriene C4 (LTC4).

Chapter 14: Biology of Mast Cells and Their Mediators
Middleton’s Allergy Principles and Practice, 8th ed.

Question 6

6. The generation of IP3 following IgE dependent mast cell stimulation leads to:
   A. activation of the NOD2 pathway.
   B. activation of the sodium calcium transporter on the rough endoplasmic reticulum.
   C. Ca2+ mobilization from the rough endoplasmic reticulum and influx of extracellular Ca2+
   D. efflux of intracellular Ca2+ and storage of Ca2+ in the rough endoplasmic reticulum.

Answer 6

6. A, activation of the NOD2 pathway, p. 234.
   IgE receptor activation initiates receptor aggregation with lipid rafts containing Lyn. Lyn kinase transphosphorylates tyrosine residues on the ITAMS binding to phosphorylated Fc(epsilon)R(beta)1 ITAM through the Src homology 2 domain. Syk protein tyrosine kinases are recruited to the rafts and bind the phosphorylated ITAMS. They are then phosphorylated to recruit Lyn and Syk promoting an activation loop. This results in fully activated Syk, starting a cascade that activates inositol triphosphate (IPs). IP3 induced Ca 2+ mobilization from the rough endoplasmic reticulum stores which initiates influx of extracellular Ca2+, a critical requirement for the release of preformed and newly generated mediators.

Chapter 14: Biology of Mast Cells and Their Mediators
Middleton’s Allergy Principles and Practice, 8th ed.

Question 7

7. Mast cells are thought to skew T cell development towards which phenotype?
A. Th1
B. Th2
C. Th17
D. Treg

Answer 7

7. B, Th2, p. 237.
   Rat mast cells can skew T cell differentiation towards a Th2 phenotype through IL-4 release. Mast cells also influence the development of dendritic cells and their ability to activate T
   cells. Histamine increases IL-10 and decreases IL-12 production by mature dendritic cells, polarizing naïve T cells towards a Th2 phenotype.

Chapter 14: Biology of Mast Cells and Their Mediators
Middleton’s Allergy Principles and Practice, 8th ed.

Question 8

8. Anaphylaxis is primarily mediated by
A. eosinophils and basophils.
B. mast cells and basophils.
C. mast cells and eosinophils.
D. neutrophils and eosinophils.

Answer 8

8. A, mast cells and basophils, p. 237.
   Anaphylaxis is mediated primarily by mast cells and perhaps basophils.

Chapter 14: Biology of Mast Cells and Their Mediators
Middleton’s Allergy Principles and Practice, 8th ed.

Question 9

9. The percentage of which type of mast cell is increased in the skin of patients with atopic dermatitis?
A. MCTC
B. MCTCT
C. MCT
D. MCC

Answer 9

9. C, MCT, p. 239
   Healthy skin contains mast cells that are approximately 90% MCTC. The number of MCT is increased in the skin of patients with atopic dermatitis.

Chapter 14: Biology of Mast Cells and Their Mediators
Middleton’s Allergy Principles and Practice, 8th ed.

Question 10

10. Aspirin-triggered asthma is associated with?
A. Increased LTE4 in nasal secretions
B. Increased LTE4 in urine
C. Decreased PGD2 in urine
D. Increased PGD2 in urine

Answer 10

10. B, Increased LTE4 in the urine, p. 241.
    Aspirin-triggered asthma is associated with increased LTC4 in the nasal secretions and increased LTE4 in the urine.

Chapter 14: Biology of Mast Cells and Their Mediators
Middleton’s Allergy Principles and Practice, 8th ed.

Question 11

1. Where do the basophils develop?
A. Bone marrow
B. Fetal liver
C. Liver
D. Thymus

Answer 11

1. A, Bone marrow, p. 252.
   Like all granulocytes, basophils are of myeloid origin, developing from pluripotent stem cell precursors found in the bone marrow.

Chapter 15: Biology of Basophils
Middleton’s Allergy Principles and Practice, 8th ed

Question 12

2. Which precursor cells differentiate into cells that morphologically and functionally resemble basophils?
A. CD4+
B. CD8+
C. CD19+
D. CD34+

Answer 12

2. D, CD34+, p. 252.
   CD34+ precursor cells, when cultured in the presence of IL-3, differentiate into cells that morphologically and functionally resemble basophils.

Chapter 15: Biology of Basophils
Middleton’s Allergy Principles and Practice, 8th ed

Question 13

3. Which of the following cytokines play a significant role in the survival and activation of mature basophils?
A. IL-3
B. IL-4
C. IL-5
D. IL-13

Answer 13

3. A, IL-3, p. 252.
   IL-3 plays a significant role in the survival and activation of mature basophils. This is a
   functional consequence of these cells’ retaining the expression of IL-3 receptors (CD123) at
   remarkably high levels.

Chapter 15: Biology of Basophils
Middleton’s Allergy Principles and Practice, 8th ed

Question 14

4. If there is an exposure to an allergen, the bone marrow activates and increases the production of the following cells:
A. Basophils and eosinophils
B. Basophils and mast cells
C. B cells and eosinophils
D. B cells and mast cells

Answer 14

4. A, Basophils and eosinophils, p. 253.
   The frequencies of these precursor cells are increased in asthmatics and in subjects who
   have undergone experimental allergen provocation, suggesting a positive feedback
   mechanism by which exposure to allergen results in bone marrow activation and increased
   production of both basophils and eosinophils.

Chapter 15: Biology of Basophils
Middleton’s Allergy Principles and Practice, 8th ed

Question 15

5. Basophils have the ability to infiltrate into tissue sites. These “rolling” events are remediated through the expression of which of the following?
   A. β1- and β2-integrin
   B. β1-integrin very late antigen (VLA)-4
   C. Intracellular adhesion molecules (ICAMs)
   D. L-selectin (CD62L)

Answer 15

5. D, L-selectin (CD62L), p. 253.
   As with other leukocytes, the initial steps of basophil attachment to endothelium occurs during “rolling” events, in which selectins play a critical role. This is mediated through the expression of L-selectin (CD62L), which attaches to the ligands CD34 and MAdCAM-1.

Chapter 15: Biology of Basophils
Middleton’s Allergy Principles and Practice, 8th ed

Question 16

6. Which of the following cytokines inhibits the priming effects that IL-3 has on basophil function?
A. IFN-β
B. IFN-γ
C. GM-CSF
D. TNF

Answer 16

6. A, IFN-β, p. 254.
   Basophils express the major receptor (IFNαR1) that binds these cytokines, and both IFN-α
   and IFN-β inhibit the priming effects that IL-3 has on basophil function.

Chapter 15: Biology of Basophils
Middleton’s Allergy Principles and Practice, 8th ed

Question 17

7. How do basophils provide signals for B cells to produce IgE?
   A. Expressing CD32 and secreting IL-4 and IL-13
   B. Expressing CD40L and secreting IL-4 and IL-13
   C. Expressing CD63 and secreting IL-4 and IL-13
   D. Expressing CD203c and secreting IL-4 and IL-13

Answer 17

7. B, Expressing CD40L and secreting IL-4 and IL-13, p. 254.
   By expressing CD40L and secreting IL-4 and IL-13, basophils have the potential to provide the two necessary signals for B cells to produce IgE.

Chapter 15: Biology of Basophils
Middleton’s Allergy Principles and Practice, 8th ed

Question 18

8. Which of the following markers has been used as a means for
determining basophil activation?
A. CD11c/CD18
B. CD40L and CD23
C. CD63 and CD203c
D. CD117 and CD32

Answer 18

8. C, CD63 and CD203c, p. 254.
   In recent years, the increased surface expression of CD63 and CD203c has been widely used as a means for determining basophil activation.

Chapter 15: Biology of Basophils
Middleton’s Allergy Principles and Practice, 8th ed

Question 19

9. Which of the following basophil receptors is associated with innate immunity?
A. CCR3
B. IL-1 like receptor
C. Receptors for prostacyclin
D. Toll-like receptors

Answer 19

9. D, Toll-like receptors, p 255.
   Basophils have recently been found to express two additional types of innate immunity associated receptors: (1) Toll-like receptors (e.g., TLR1, -2, -4, -6, -9), which bind a variety of microbial products, and (2) leukocyte immunoglobulin-like receptors (e.g., LIR3, -7), for which the natural ligands have not yet been identified.

Chapter 15: Biology of Basophils
Middleton’s Allergy Principles and Practice, 8th ed

Question 20

10. Mast cells and basophils differ with respect to the mediators they release. Which of the following is not secreted by basophils on FcεRI-mediated activation?
A. Histamine
B. IL-3
C. LTC4
D. PGD2

Answer 20

10. D, PGD2, p. 260.
    Ultimately, in vitro studies showed that mast cells and basophils differ with respect to the mediators they release and the way in which they respond to various stimuli. For example, mast cells secrete PGD2 on FcεRI-mediated activation, whereas basophils do not.

Chapter 15: Biology of Basophils
Middleton’s Allergy Principles and Practice, 8th ed

Question 21

1. Which of the following substances are contained within eosinophilic “specific” or secondary granules?
A. Acid phosphatase
B. CD11b
C. Charcot-Leyden crystal protein
D. Major basic protein

Answer 21

1. D, Major basic protein, p. 255-257.
   Primary granules contain Charcot Leyden crystal protein. Secondary granules contain major basic protein, eosinophilperoxidase, eosinophil cationic protein,
   and eosinophil derived neurotoxin. Small granules contain acid phosphatase and arylsulfatase. Secretory vesicles contain membrane bound cytochrome b558, CD11b, albumin, and the alpha chain or beta-2 integrin.

Chapter 16: Biology of Eosinophils
Middleton’s Allergy Principles and Practice, 8th ed.

Question 22

2. Eosinophil production and lineage differentiation is dependent on which transcription factor?
A. GATA-1
B. GATA-3
C. GATA-6
D. GATA-8

Answer 22

2. A, GATA-1, p. 255.
   Production of eosinophils depends on different transcription factors including GATA-1, PU.1, and C/EBP members. PU.1 determines distinct cell lineage fates and GATA-1 and PU.1 synergistically induce eosinophil lineage differentiation. GATA-1 binding site deletion in mice has demonstrated a specific loss of eosinophils.

Chapter 16: Biology of Eosinophils
Middleton’s Allergy Principles and Practice, 8th ed.

Question 23

3. Eosinophil proliferation and differentiation is dependent upon interleukin-3 (IL3), granulocyte-macrophage colony-stimulating factor (GM-CSF), and interleukin-5
   (IL-5).
   Committed eosinophil precursors in the bone marrow can be identified by their expression of which of the following?
   A. IL-3 receptor and CCR5
   B. IL-3 receptor and CCR7
   C. IL-5 receptor and CCR3
   D. IL-5 receptor and CXCL13

Answer 23

3. C, IL-5 receptor and CCR3, p. 255.
   In the bone marrow, committed eosinophil precursors can be identified by their expression of IL-5 receptor alpha chain (CD125) and the chemokine receptor CCR3.
   Chapter 16: Biology of Eosinophils
   Middleton’s Allergy Principles and Practice, 8th ed.

Question 24

4. Under normal physiologic circumstances eosinophils are primarily located in tissues including the thymus, uterus, mammary glands, and gastrointestinal tract (except the esophagus) where their life span is about 2-5 days. In the peripheral blood, eosinophil
   half-life is about 8-18 hours.
   Measurement of eosinophils in the blood are the highest at what time of day?
   A. Early morning
   B. Evening
   C. Late morning
   D. Mid afternoon

Answer 24

4. B, Evening, p. 257.
   Eosinophils exhibit diurnal variation. In the peripheral blood, the lowest levels are generally detected in the morning and the highest levels are seen in the evening.
   Chapter 16: Biology of Eosinophils
   Middleton’s Allergy Principles and Practice, 8th ed.

Question 25

``` 5. In patients with asthma, the correlation between the concentration of which specific granule protein, measured in bronchoalveolar lavage fluid with the severity of bronchial hyper-reactivity is observed? A. Eosinophil cationic protein B. Eosinophil derived neurotoxin C. Eosinophil peroxidase D. Major basic protein ```

Answer 25

5. D, Major basic protein, p. 258. Major basic protein (MBP) has several roles; it disrupts Schistosoma membrane and is toxic to Trichinella, Trypanosoma, Staphylococcus aureus, E. coli and tumor cells. The concentration of MBP in the bronchoalveolar lavage (BAL) fluid has been correlated with bronchial hyperreactivity in patients with asthma. MBP also increases airway responsiveness to inhaled methacholine. Eosinophil cationic protein has neurotoxic and antiviral properties. Eosinophil-derived neurotoxin is extremely neurotoxic; it also enhances Th2 responses through TLR-2 dependent mechanisms. Eosinophil peroxidase along with hydrogen peroxide and halide is anti-microbial against several pathogens. Chapter 16: Biology of Eosinophils Middleton's Allergy Principles and Practice, 8th ed.

Question 26

``` 6. Which of the following lipid mediators is the predominant metabolite of the 5-lipoxygenase pathway, generated by eosinophils? A. LTB4 B. LTC4 C. LTD4 D. LTE4 ```

Answer 26

6. B, LTC4, p. 258. In eosinophils, the predominant metabolite of the 5-lipoxygenase pathway is LTC4, which in turn, is metabolized to LTD4 and LTE4. Eosinophils also produce large amounts of 5- HETE. Together, these mediators lead to contraction of smooth muscle airways, mucus secretion, and eosinophil and neutrophil infiltration into tissues. Chapter 16: Biology of Eosinophils Middleton's Allergy Principles and Practice, 8th ed.

Question 27

``` 7. Monoclonal anti-IL-5 therapies for asthma exert several effects on the biology of eosinophils. Which of the following eosinophil-derived substances induces tissue damage and remodeling? A. LTC4 B. MBP, ECP, EDN, EPX C. RANTES and GM-CSF D. TGF-beta and MMP-9 ```

Answer 27

7. D, TGF-beta and MMP-9, p. 258, figure 16.5. In the pathogenesis of asthma: MBP, ECP, EDN, and EPX induce epithelial injury, MMP9 induces tissue damage and remodeling, and LTC4 results in smooth muscle airway contraction. GM-CSF and RANTES are cytokines/chemokines which enhance eosinophil recruitment and activation. TGF-beta induces tissue remodeling and fibrosis. Anti-IL-5 therapies reduce the pathologic effects of these substances. Chapter 16: Biology of Eosinophils Middleton's Allergy Principles and Practice, 8th ed.

Question 28

``` 8. The most potent eosinophil chemo-attractants include platelet activating factor (PAF),LTD4, C5a and CCL11 (eotaxin-1) and CCL5 (RANTES). Which of the following is most commonly implicated in the pathogenesis of eosinophilic esophagitis? A. eotaxin-1 B. LTD4 C. PAF D. RANTES ```

Answer 28

8. A, eotaxin-1, p. 262. PAF is a potent and effective chemoattractant for eosinophils and also evokes the release of granule proteins from eosinophils. LTD4 is a chemoattractant for eosinophils which can be blocked by CysLT1 antagonists. Chapter 16: Biology of Eosinophils Middleton's Allergy Principles and Practice, 8th ed.

Question 29

``` 9. Extracellular release of eosinophil granule contents is a major effector function, implicated in host defense and pathologic disease processes. Which of the following granule release forms involves granule fusion with the cell membrane, leading to sudden large increments in release? A. Compound exocytosis B. Cytolysis C. Piecemeal degranulation D. Sequential release ```

Answer 29

9. A, Compound exocytosis, p. 262. Compound exocytosis results in sudden, large increments in capacitance which leads to individual granule fusion with the cell membrane. Sequential release is seen in vitro and is demonstrated with a patch-clamp technique. Piecemeal degradation involves numerous small vesicles budding off from larger granules and moving to the plasma membrane for fusion. Cytolysis is a not well understood mechanism. Chapter 16: Biology of Eosinophils Middleton's Allergy Principles and Practice, 8th ed.

Question 30

10. In addition to protection from helminths, eosinophils are purported to serve a role against certain viral infections. In the respiratory tracts of patients infected with which of these viruses can an increase in eosinophil number and concentration of eosinophil granule proteins be found? A. Adenovirus B. Influenza A C. Respiratory syncytial virus D. Rhinovirus

Answer 30

10. C, Respiratory syncytial virus, p. 264. There are increased numbers of eosinophils and increased concentration of eosinophil granule proteins in the respiratory tracts of patients with Respiratory syncytial virus (RSV). In animal models infected with parainfluenza, treatment with anti-IL-5 and subsequent reduction in eosinophil levels lead to an increase in viral content in the airways. Chapter 16: Biology of Eosinophils Middleton's Allergy Principles and Practice, 8th ed.

Question 31

2. Th17 cells release which of the following? 1. IFN-gamma 2. IL-2 3. IL-9 4. IL-22

Answer 31

2. D, IL-22, p. 329, Figure 21-3. Th17 cells release IL-17 and IL-22. Th1 cells release IL-2 and IFN-gamma . Th9 cells release IL-9. Chapter 21: Pathophysiology of Allergic Inflammation Middleton's Allergy Principles and Practice, 8th ed.

Question 32

``` 1. Which of the following is released by epithelial cells to maintain mucosal mast cells at the airway and skin surface? A. CCL17 B. CCL22 C. IL-9 D. Stem cell factor (SCF) ```

Answer 32

1. D, Stem cell factor (SCF), p. 328, Figure 21-2. Epithelial cells release stem cell factor to maintain mucosal mast cells. CCL17 and CCL22 are released by epithelial cells to act on CCR4 to attract Th2 cells. IL-9 is released by Th2 cells to stimulate mast cell proliferation. Chapter 21: Pathophysiology of Allergic Inflammation Middleton's Allergy Principles and Practice, 8th ed.

Question 33

``` 1. Which cell type is thought to be primarily responsible for clearance of apoptotic cells? A. Eosinophils B. Macrophages C. Mast cells D. Neutrophils ```

Answer 33

1. B, Macrophages. Macrophages are the primary cells responsible for engulfment of apoptotic cells and apoptotic bodies Chapter 25: Resolution of Allergic Inflammation Middleton's Allergy Principles and Practice, 8th ed