Middleton's Allergy 9th Edition Questions

1. What signaling pathway is associated with chemokine receptor internalization? a. β-arrestin b. Gα c. Src kinase d. MAPK e. SHP2

1. Answer: a. β-arrestin pathways induce chemokine receptor internalization. Gαi pathways promote chemotactic responses and MAPK pathways can be activated downstream of Gαi signaling. Src kinase signaling and SHP2 pathways may enhance CCR7 chemotactic responses.

1. Which lymphocytes constitute the adaptive immune system? a. Natural Killer cells b. T lymphocytes c. Gamma delta T cells d. B lymphocytes e. Innate lymphoid cells

1. Answer: b and d. T and B lymphocytes are activated upon activation by cognate antigens, and this constitutes the adaptive immune system.

1. Which statement best describes the full array of outdoor aeroallergen sources? a. Airborne environmental allergens are typically derived from pollen grains and fungal spores. b. Outdoor aeroallergens can originate from multiple sources, including plants, for example pollen grains; fungi, such as mold spores; and animals, such as dander. c. Outdoor allergens can originate from pollen grains of grasses, weeds, trees and a variety of families of fungal spores. d. Outdoor aeroallergen sources include plants or detritus. e. Grasses are the main sources of airborne pollen allergens

1. Answer: b.

1. Which of the following is required for innate lymphoid cell (ILC) 2 development? a. Aryl hydrocarbon receptor (AHR) b. Inhibitor of DNA binding 2 (Id2) c. Eomesodermin (EOMES) d. Recombination-activating genes (RAG)

1. Answer: b. All ILCs originate from multipotent common lymphoid progenitors (CLPs) that form early innate lymphoid progenitors and require inhibitor of DNA binding 2 (Id2).

1. Which Th2 cytokine is unique in its ability to induce eosinophilopoiesis from CD34+ progenitor cells? a. IL-4 b. IL-5 c. IL-9 d. IL-13

1. Answer: b. Although many cytokines can help eosinophils mature and become fully functional, only IL-5 is able to convert immature progenitors and direct them down the eosinophil development pathway. This is one reason why biologics are being developed that target this molecule for treatment of allergic disease

1. Induction of CD4 Th2 immunity is a specific function of: a. Alveolar macrophages. b. Type 2 dendritic cells. c. Plasmacytoid dendritic cells. d. Epithelial cells.

1. Answer: b. Alveolar macrophages and plasmacytoid DCs are known to suppress Th2 induction. Epithelial cells are not able to present antigens to CD4 T cells in an immunogenic manner.

1. What is the primary source of inhaled dust mite allergen? a. Urine b. Feces size 15 to 30 microns in diameter c. Secretions d. Fragments of feces size 2 to 7 microns in diameter

1. Answer: b. Feces size 15 to 30 microns in diameter have been shown to be the primary form in which dust mite allergens become airborne, and because of their peritrophic membrane they do not break up.

1. Prostaglandin D2 can be generated through the sequential actions of which of the following 2 enzymes: a. Cyclooxygenase-1 and prostaglandin E synthase b. Cyclooxygenase-1 and prostaglandin D synthase c. 5-Lipoxygenase and prostaglandin D synthase d. 12-Lipoxygenase and prostaglandin E synthase

1. Answer: b. For PGD2 generation, arachidonic acid must be first metabolized through either COX-1 or COX-2, and then further through prostaglandin D synthase

1. GATA3 is a key transcription factor in which of the following cells? a. Airway epithelial cells b. ILC2 cells c. Macrophages d. Th17 cells

1. Answer: b. GATA3 is expressed predominantly in Th2 and ILC2 cells and regulates their differentiation and secretion of T2 cytokines.

1. Which of the following describes the systematic analysis of proteins for their identity, quantity, and function? a. Genomics b. Proteomics c. Epigenetics d. Pharmacogenetics

1. Answer: b. Genomics is the analysis of genes. Epigenetics studies the modifications in response to transient environmental signals. Pharmacogenetics examines the interindividual variations in the DNA sequence related to drug absorption, disposition, and action.

1. Which of the following has a major role in the development of protective immunity induced by childhood immunizations? a. Eosinophils b. B cells c. NK cells d. Neutrophils e. Basophils

1. Answer: b. T and B cells are components of the adaptive immunity. Eosinophils, neutrophils, NK cells, and basophils are considered components of the innate immunity

1. Which of the following statements aligns with the systems biology approach? a. Develop a hypothesis and run experiments to test it b. Gather as much information as possible and use a data-driven approach to generate hypotheses c. Reliance on extensive literature review only to develop a hypothesis d. None of the above

1. Answer: b. Unlike other approaches that are hypothesis-driven or literature-based, a systems biology approach is best described as data-driven

1. Complex diseases such as asthma are common and involve: a. Many genes, with "severe" mutations leading to large phenotypic effects with strong environmental interactions. b. Few genes, with "mild" mutations leading to small phenotypic effects with strong environmental interactions. c. Many genes, with "mild" mutations leading to small phenotypic effects with strong environmental interactions. d. Many genes, with "mild" mutations leading to large phenotypic effects with limited environmental interactions. e. Few genes, with "mild severe" mutations leading to small large phenotypic effects with strong limited environmental interactions

1. Answer: c. Asthma is a classic complex disorder involving both genetic and environmental factors leading to disease. The genetic factors identified span many genes and are small in magnitude of individual effect sizes.

1. Which of the following pairs of statements concerning arthropod allergens is correct? a. Der p 2 allergen - a cysteine protease structurally similar to papain. b. Cockroach tropomyosin - a marker allergen for cockroach allergy. c. Bla g 2 - a pseudoprotease. d. Arginine kinases - a group of allergenic enzymes restricted to Lepidoptera species.

1. Answer: c. Bla g 2 is similar in sequence to known aspartate proteases but does not appear to demonstrate protein cleaving capacity, hence the name "'pseudoprotease'."

1. An immunologist in the laboratory adds IL-4 to a suspension of highly purified B cells in an effort to induce IgE production but is surprised to find no IgE in the culture supernatant 8 days later. How could she get this to work better next time? a. She should add IL-13, which is a better inducer of IgE production. b. Including antibiotics in the medium would prevent bacterial contamination and give a better result. c. Adding some activated T cells would help push the B cells into IgE production. d. Antigen-presenting cells should be included in the culture to get the B cells to switch.

1. Answer: c. In addition to the cytokine signal, which can be provided by IL-4 or IL-13, B cells require a costimulatory signal most commonly provided by CD40L (CD154) expressed on activated T cells. This engages CD40 on the B cell and provides signals that t

1. Immune responses can be triggered in human airway epithelial cells in response to inhaled viruses, bacteria, fungi, and environmental pollutants. Which class of receptors orchestrate innate immune responses to these stimuli? a. Interleukin-1 receptor family b. Adrenergic receptors c. Pattern recognition receptors d. Glucocorticoid receptors

1. Answer: c. Pattern recognition receptors are germline encoded and able to recognize pathogen-associated and damage-associated molecular patterns to initiate innate immune responses that may include cytokine, chemokine, or interferon production.

1. Which of the below describes central tolerance for T cells? a. Negative selection b. Deletion of self-reactive T cells c. Development of natural Treg cells in the thymus d. All of the above

1. Answer: d

1. Which of the following statements regarding immunoglobulin structure and expression is true? a. An individual naïve B cell expresses surface IgM molecules that include both kappa and lambda light chains. b. Surface IgM is expressed on B cells as a pentamer. c. Surface immunoglobulin on B cells requires binding to B cell Fc receptors. d. Serum IgA can exist as a dimer. e. Antibodies expressing kappa light chains exhibit enhanced ability to fix complement.

1. Answer: d. A is incorrect because an individual B cell expresses kappa or lambda light chains, but never both. B is incorrect because surface IgM (all classes and subclasses) is always a monomer. C is incorrect because immunoglobulin is expressed on the surface of B cells as a result of a transmembrane domain in the heavy chain. E is incorrect because light chains do not play a role in the effector function of antibodies. D is the correct answer as serum IgA can exist as either a monomer or a dimer.

1. Opsonization is a key function of the complement cascade. Which component represents the opsonin? a. C1 b. C2 c. C4 d. C3 e. C5

1. Answer: d. Cleavage of C3 and deposition of C3b onto the surface of a pathogen renders it more easily phagocytosed.

1. Activation of nerves can both contract and relax airway smooth muscle. What type of nerve is most responsible for evoking smooth muscle relaxation of human bronchial smooth muscle? a. Postganglionic sympathetic adrenergic nerves b. Postganglionic parasympathetic cholinergic nerves c. Spinal DRG-derived afferent C-fibers d. Postganglionic parasympathetic nerves releasing vasoactive intestinal peptide and nitric oxide e. Vagal afferent C-fibers

1. Answer: d. In some species the airways are innervated by sympathetic adrenergic nerves that can lead to relaxation of smooth muscle via activation of beta adrenoceptors. Human airway smooth muscle, however, does not receive adrenergic innervation, but is instead innervated by a subtype of parasympathetic nerves that release vasoactive intestinal peptide (VIP) and nitric oxide (NO) upon activation. VIP and NO are the neurotransmitters regulating human airway smooth muscle relaxation.

1. Which of the following are properties of the adhesion molecule CADM1? a. CADM1 is a Ca2+-dependent integrin. b. CADM1 works independently of Kit to regulate MC survival. c. CADM1 is expressed as a single functional isoform. d. CADM1-dependent adhesion promotes MC survival and proliferation in co-culture with airway smooth muscle cells and lung fibroblasts. e. CADM1 is expressed widely on healthy leukocytes.

1. Answer: d. Inhibition of CADM1 with neutralizing antibodies or RNA silencing reduces mast cell survival and proliferation in coculture with airway smooth muscle cells and lung fibroblasts. A: It is a Ca2+ -independent Ig superfamily member. B: CADM1 interacts intimately with Kit. C: CADM1 is expressed as several splice variants with distinct functions. E: CADM1 expression is restricted to mast cells amongst healthy leukocytes.

1. Which of the following statements is accurate? a. MyD88/TRAM pathway is required for all TLR signaling. b. The TRIF/TRAM pathway leads to activation of NF-κB. c. Inflammasome activation and the generation of mature IL-1B is elicited by TLR signaling. d. Viral nucleic acid is recognized by both NLRs and RIG-I. e. Endocytosis is the primary function of C-type lectin receptors

1. Answer: d. Viral nucleotides can be recognized by NLRP3 in addition to RIG-I. TLR activation can trigger the MyD88/TIRAP pathway for NF-κB activation or the TRIF/TRAM pathway for interferon generation. TLRs do not activate the inflammasome. CLRs have many functions. Their importance in antifungal immunity relies on activation of pro-Th17 cytokine generation.

1. Which of the following adhesion molecules is expressed by leukocytes and mediates their firm adhesion to endothelium? a. L-selectin b. E-selectin c. PSGL-1 d. β1 integrin

1. Answer: d. β1 integrins expressed by leukocytes mediate firm adhesion to endothelium. Selectins mediate rolling, not firm adhesion. E-selectin is expressed by endothelium and not leukocytes; E-selectin mediates rolling, not firm adhesion. PSGL-1 binds to P-selectin and mediates rolling, not firm adhesion.

1. Airway smooth muscle growth and proliferation is modulated by the following receptors: a. Platelet-derived growth factor receptor b. CysLT receptors c. Histamine receptors d. None of the above e. All of the above

1. Answer: e. Each type of receptor has the ability to modulate airway smooth muscle growth and proliferation whether it is a growth factor receptor or a receptor for a contractile agonist.

2. The airway epithelium forms a pseudostratified barrier tissue that consists of multiple cell types. Which of the following cell types are not part of the pseudostratified epithelium? a. Innate lymphoid cells b. Basal cells c. Columnar cells d. Club cells

2. Answer: a. Although innate lymphoid cells are associated with the airway epithelium and able to respond to epithelium-derived cytokines (e.g., TSLP, IL-33), they are not strictly speaking part of the pseudostratified epithelium because they are of lymphoid origin.

2. Dendritic cells and epithelial cells communicate with each other via: a. Thymic stromal lymphopoietin (TSLP) and granulocyte macrophage colony-stimulating factor (GM-CSF). b. GM-CSF and interleukin 8 (IL-8). c. Neuropeptides. d. Gap junctions.

2. Answer: a. Interleukin 8 is involved in communication with neutrophils only. Neuropeptides are not made abundantly during the interaction between DCs and epithelial cells. Gap junctions are mainly involved in interactions between epithelial cells

2. Which of the following are rare but potentially fatal complications of natalizumab (antialpha 4 integrin antibody)-based antiadhesion therapy in multiple sclerosis? a. Progressive multifocal leukoencephalopathy (PML) b. Coronary thrombosis c. Stroke d. Renal failure

2. Answer: a. Natalizumab likely causes PML by blocking T lymphocytes being recruited from the circulation to the brain, where John Cunningham virus is activated to cause PML (see references 59 and 60).

2. Which of the following applies to whole exome sequencing? a. A next generation sequencing method to sequence the coding regions of the genome b. A comprehensive technique to sequence the entire genome c. A next generation sequencing approach with the highest cost and the most complex analysis d. Can provide information on a disease-causing intronic variation

2. Answer: a. The technique to sequence the entire genome is whole genome sequencing, which has the highest cost and the most complex analysis. Targeted gene panel sequencing can provide information on a disease causing intronic variation, unlike whole exome sequencing, which does not examine noncoding regions, or introns

2. Which T helper (Th) subset is most commonly associated with allergic disease? a. Th1 b. Th2 c. Th9 d. Th17 e. Treg

2. Answer: b. Allergens preferentially induce differentiation of naïve CD4+ T cells or T helper (Th) cells to Th2 cells.

2. Which chemokine receptor is critical for the recruitment of eosinophils and basophils? a. CCR2 b. CCR3 c. CCR4 d. CXCR5 e. CXCR1

2. Answer: b. CCR3 is the main chemokine receptor promoting eosinophil and basophil migration. CCR2 is associated with inflammatory monocytes, CCR4 promotes lung homing and Th2 cell migration, CXCR5 promotes B cell and Tfh cell migration into B cell follicles, and CXCR1 is a neutrophil chemotactic receptor.

2. Which neutrophil granule product exploits a structural difference in the cellular membrane organization between bacterial and mammalian cells for its microbicidal activity? a. Myeloperoxidase b. Human α-defensins c. Neutrophil elastase d. Cathepsin G

2. Answer: b. Human α-defensins are antimicrobial peptides with a specific amphipathic structure that allows them to integrate into areas of the membranes enriched with negatively charged phospholipids. Although the cell membranes of bacteria, viruses, and fungi are enriched with negatively charged phospholipid headgroups, mammalian cell membranes lack polar phospholipids rendering them "resistant" to antimicrobial activity.

2. A 33-year-old man comes to clinic complaining of a history of Candida and Staphylococcus aureus infections. Measurement of IgE shows markedly elevated levels and a flow cytometry panel demonstrates a lack of Th17 cells. To determine the diagnosis, you decide to order sequencing of which of the following genes? a. STAT1 b. STAT3 c. STAT4 d. STAT6

2. Answer: b. Many mutations and immune processes can lead to presentations of mucocutaneous candidiasis; however, it is autosomal dominant mutations of the STAT3 gene that results in the absence of Th17 cells that then results in recurrent Candida and Staphylococcus aureus infections with elevated or "hyper" IgE levels

2. Which analysis incorporates genomic and transcriptomic data, incorporating the information of gene locations on chromosomes? a. Genome-wide association study (GWAS) b. Expression quantitative trail loci (eQTL) mapping c. Differential gene expression d. Gene coexpression network analysis

2. Answer: b. Out of the list, only eQTL mapping requires two distinct types of high-throughput data—genotype data and gene expression data (RNAseq, gene expression microarray, etc.). GWAS and differential gene expression each incorporate two types of data—genotype or gene expression data, respectively, and outcome data. Gene coexpression network analysis requires only one type of data—gene expression.

2. How might allergic inflammation alter function in the central nervous system if the allergen cannot gain access to the brain? a. By increasing IL-5 systemically, which then crosses the bloodbrain barrier to alter neuronal function. b. By persistently stimulating nociceptors in a manner that can lead to a process known as central sensitization. c. By evoking histamine release from tissue mast cells that reaches the brain where it activates H4 receptors. d. By elevating the numbers of eosinophils in the blood that then gain access to the brain, where they release cationic proteins to alter nerve function.

2. Answer: b. When nociceptive C-fibers are persistently activated, the release of transmitters from their central terminals can lead to a series of signaling events that ultimately increases the synaptic efficacy at the level of second order neurons in the CNS. This process is referred to as central sensitization. Central sensitization can lead to gross exaggerations in the responses to subsequent sensory stimulation

2. Leukotriene C4 can be generated through the sequential actions of which of the following two enzymes: a. Cyclooxygenase-2 and leukotriene C4 synthase b. 5-Lipoxygenase and leukotriene A4 hydrolase c. 5-Lipoxygenase and leukotriene C4 sy

2. Answer: c. For LTC4 generation, arachidonic acid must be first metabolized through 5-LO, and then through leukotriene C4 synthase

2. Which of the following is present on human innate lymphoid cell (ILC) 2s? a. CD3 b. CD20 c. CD45 d. CD56

2. Answer: c. ILC2s are derived from hematopoietic cells and express CD45. ILC2s are lineage-negative cells and therefore do not express CD3 (T cell marker), CD20 (B cell marker), or CD56 (natural killer cell marker).

2. Cross-linking of the high-affinity IgE receptor, FcεRI, by IgE binding to polyvalent allergens initiates a series of intracellular signaling events. Which of the following statements is correct with regard to those signaling pathways? a. FcεRI is a multisubunit ion channel that, upon ligand binding, allows Ca2+ ions to flow into mast cells or basophils. b. Activation of the receptor leads to phosphorylation of ITAM motifs in the b and g chains with subsequent recruitment of the signaling kinase, ZAP-70. c. Constitutively receptor-associated kinases, including LYN, are important both in initiating signaling and in bringing it under control. d. In the presence of its ligand, IgE, levels of FcεRI are downregulated on the cell surface

2. Answer: c. Lyn (and fyn) kinases associated with FcεRI are responsible both for phosphorylating the cytosolic ITAM motif that becomes a docking site for Syk, the key signaling kinase of the FcεRI signaling pathway, and for activating the inhibitory kinase, Cbp. Although FcεRI activation leads to Ca2+ increases, the receptor is not, itself, an ion channel and, instead, works by activating the generation of intermediates, including DAG, that trigger the release of Ca2+ from the endoplasmic reticulum. ZAP-70 is the ITAM-binding signaling kinase in T cells, serving a function identical to that of Syk in B cells and mast cells/basophils. IgE antibodies lead upregulation of their receptor levels.

2. Which of the following applies to the action of β2-adrenoceptor agonists on mast cells (MCs) and airway smooth muscle cells? a. They are effective at inhibiting MC activation when administered chronically to patients with asthma. b. Their activity is enhanced after MC exposure to stem cell factor (SCF). c. They inhibit IgE-dependent mast cell activation when applied acutely in vitro, but not activation induced by airway smooth muscle contact in vitro. d. They prevent airway smooth muscle contraction in coculture with MCs. e. β2-adrencoeptor agonists do not inhibit human lung MC migration.

2. Answer: c. See reference 251. A: With regular dosing, mast cell activation is not inhibited in vivo; for example, the early response to allergen challenge is no longer inhibited after 1 week of treatment with salbutamol or salmeterol. B: SCF phosphorylates the β2- adrenoceptor at Tyr350, leading to receptor uncoupling and loss of β2-agonist activity. D: In coculture, the β2-adrenoceptor in ASM cells is phosphorylated at Tyr350, leading to receptor uncoupling and loss of β2-agonist activity. E: β2-adrenoceptor agonists are effective inhibitors of human lung MC migration, likely through their ability to close the KCa3.1 ion channel.

2. Cat allergens become airborne on particles coming off the skin. What characteristics determine the symptoms related to cat exposure? a. The absolute weight of the particles b. The aerodynamic size of the particles, which is greater than that of mite feces and so delivers larger quantities of the allergen c. The aerodynamic size of the particles, which allows particles carrying cat allergen to remain airborne for many hours d. The breed of cat

2. Answer: c. The aerodynamic size of particles carrying cat allergens allows them to remain airborne for several hours in an undisturbed room

2. Which of the following cytokines function as an alarmin? a. IL-17 b. IL-10 c. GM-CSF d. IL-33

2. Answer: d. Alarmins are released from epithelial cells in response to injury of infection and lead to type 2 immunity with activation of Th2 and ILC2 cells. The key alarmins involved in allergy are TSLP, IL-25, and IL-33.

2. Which of the following statements about pollen allergens is incorrect? a. The group 1 allergens, such as Phl p 1, represent useful marker allergens in diagnosing grass pollen allergy. b. Pectate lyase allergens are found in gymnosperm tree pollen species as well as in Asteraceae species. c. The majority of ragweed allergens are associated with subpollen particles. d. The group 1 allergens from trees belonging to the Fagales order possess polygalacturonase activity

2. Answer: d. Allergenic arginine kinases can be found in crustaceans as well as in mites and a variety of insects, not just those belonging to the order Lepidoptera (moths and butterflies).

2. Contraction of airway smooth muscle occurs through all of the following except: a. Intracellular calcium increases b. Rho-kinase-dependent mechanisms c. CD38 activation d. Growth factor receptor activation e. G-protein coupled receptor activation

2. Answer: d. Growth factor receptor activation does not activate the pathways or signaling intermediates that are associated with contraction of airway smooth muscle.

2. Which class of antibodies trigger a peanut allergic reaction? a. IgA b. IgM c. IgD d. IgE e. IgG

2. Answer: d. Immediate hypersensitivity reactions occur when antigen binds IgE molecules on mast cells. IgG, IgA, and IgM participate in antibody-mediated cytotoxicity, immune complex reactions.

2. Which of the following describes a molecular mechanism of antigenspecific immune tolerance? a. Anergy b. Deletion c. Suppression d. Immune privilege e. All of the above

2. Answer: e.

2. Which of the following statements concerning antibody class switch is correct? a. The first antibody class switch that occurs is from IgM to IgD. b. Class switch often increases the affinity of the antibody for antigen. c. A B cell that has undergone class switch from IgM to IgE can undergo a later switch to IgG1. d. A, B, and C e. None are correct

2. Answer: e. A is incorrect because IgD is not generated through class switch; instead, differential RNA processing allows a B cell to coexpress at the same time both IgM and IgD. B is incorrect because class switch does not affect the rearranged VDJ, which is responsible for antigen binding. C is incorrect because class switch from IgM to IgE permanently deletes the intervening constant region genes, which include IgG1, IgG3, IgA1, IgG2, and IgG4. E is the correct answer because answers A-C are all incorrect.

2. The first genome-wide association study (GWAS) in asthma was published in 2007 and identified which genomic region that has been replicated in all GWASs of asthma to date? a. IL6R b. TSLP c. GATA3 d. IL33 e. ORMDL3

2. Answer: e. The first GWAS in asthma was completed by Moffatt et al. (reference 35) and identified the ORMDL3 locus, a signal that that has been replicated in all GWASs of asthma to date

2. Increased susceptibility to neisserial disease is the hallmark of which set of complement deficiencies? a. Early classical pathway proteins b. Fluid phase regulatory proteins c. Solid phase regulatory proteins d. Lectin activation components e. Terminal components

2. Answer: e. The terminal components or membrane attack complex is responsible for cytolytic activity, and deficiencies are associated with an increased risk of neisserial disease.

2. What are the features of the Hirst-type pollen and spore trap that is commonly used for monitoring airborne pollen grains and fungal spores? a. A Hirst-type pollen and spore trap collects airborne pollen directly onto the surface of a microscope slide to give daily pollen counts. b. The Hirst-type pollen and spore trap is a continuous flow automatic pollen monitor that provides pollen concentrations in real time. c. The Hirst-type pollen and spore trap collects pollen for 1 minute every 10 by impaction onto a rod, which is then counted by light microscopy. d. The Hirst-type pollen and spore trap collects airborne pollen and spores by gravity onto a microscope slide. e. The Hirst-type pollen and spore trap is a continuous flow volumetric air sampling device that collects airborne pollen and spores impacted onto an adhesive surface of a 7-day drum or 24 hour microscope slide, which then requires manual counting by light microscopy to provide daily pollen concentrations

2. Answer: e. This is the only correct answer that encompasses essential features of continuous air flow, pollen, and spore particle impaction onto the adhesive surface and counting by light microscopy to provide concentration data.

3. Identify each answer that is true for how pollen identification and counting are routinely performed. a. Fuchsin is a stain that binds the outer wall (exine) of pollen, giving a deep pink color, enhancing identification of pollen by light microscopy. b. Counts of pollen and spores impacted onto a microscope slide or melinex tape are converted to concentrations in cubic meters of air based on the proportion of the impaction area counted, airflow rate of the trap, and duration of collection. c. Pollen and spores can be identified readily and counted by light microscopy with a 10× objective lens, giving a magnification of 100. d. Collected pollen and spores are identified using a light microscope based on expert knowledge of external features: size (20 to 150 μm), shape, pores, furrows, and surface sculpturing. e. Accurate identification of pollen grains by light microscopy usually requires a magnification of 400×.

3. Answer: a, b, d and e. A 10× objective lens of a light microscope does not give sufficient magnification to reliably identify key surface features of pollen or spores. Pollen is usually identified using 400× magnification, and spores may require up to 1000× magnification.

3. Which of the following statements about allergens from domesticated furry animal pets is correct? a. The dog allergen, Can f 5, is a prostatic kallikrein and shows sequence identity with human PSA. b. Lipocalin allergens such as Fel d 1 are minor allergens. c. IgE from furry animal-allergic patients is directed primarily against conformational epitopes on the surface of the IgA and IgM allergens. d. Serum albumin allergens have molecular weights in the region of about 30 kDa.

3. Answer: a. Can f 5 is a prostatic kallikrein allergen found in both dog urine and dander. It shares about 60% sequence similarity with the human prostate-specific antigen and demonstrates immunologic cross-reactivity.

3. Systemic lupus erythematosus is associated with early classical pathway component deficiencies. Which test is the best screen for an early classical pathway component deficiency? a. CH50 b. AH50 c. Whole exome sequencing

3. Answer: a. Early classical pathway defects will be identified through the CH50.

3. Which cytokine is released by necrotic epithelial cells but has also been shown to play a role in restoration of epithelial integrity and thermogenesis? a. IL-33 b. IL-25 c. Thymic stromal lymphopoietin (TSLP) d. IL-8

3. Answer: a. IL-33-mediated activation of ILC2s leads to production of amphiregulin and downstream activation of the epithelial growth factor receptor (EGFR) promoting the restoration of the epithelial barrier in the airway and gastrointestinal tract. In the adipose tissue, IL-33 activates ILC2s, eosinophils, alternatively activated macrophages, and T regulatory cells to influence thermogenesis and insulin sensitivity

3. The itchy urge to cough that is associated with airway allergic responses occurs most likely secondary to the activation of what type of nerve? a. Vagal afferent C-fibers b. Spinal afferent C-fibers c. Parasympathetic nerves d. Sympathetic nerves e. Fast conducting spinal afferent A-fibers

3. Answer: a. It has long been recognized that severing or anesthetizing the vagus nerves prevents cough arising from stimulation of nerves in the airways. The afferent (sensory) nerves in the vagi are comprised of fast conducting A fibers, and slow conducting C-fibers. Allergic inflammation is associated with the production and release of mediators that activate vagal C-fibers. Exposing human volunteers to certain inflammatory mediators known to stimulate vagal C-fibers leads to strong urge-to-cough sensations.

3. Which prostaglandin functions in chemotaxis and cytokine production of innate lymphoid cell (ILC) 2s? a. PGD2 b. PGE2 c. PGI2 d. PGF2α

3. Answer: a. PGD2 promotes chemotaxis and cytokine production by signaling through the chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2), also known as DP2.

3. Which of the following immune responses is most responsible for dermatitis associated with poison ivy exposure? a. Th1 b. Th2 c. Th3 d. Tregs e. Th17

3. Answer: a. Poison ivy exposure causes contact dermatitis, which is an example of delayed hypersensitivity, and is mediated by Th1- driven response. Th3 is not a known subset. Th2, Tregs, and Th17 are not directly associated with delayed hypersensitivity responses.

3. Recently it has been shown that childhood-onset asthma, allergic rhinitis, and atopic dermatitis share a large number of genetic risk factors; how many risk factors from the 136 identified are believed to be disease specific? a. 6 b. 12 c. 21 d. 9 e. 2

3. Answer: a. The study of Ferreira et al. 2017 (reference 93) included 180,129 cases (with asthma, allergic rhinitis, or atopic dermatitis) and 180,709 controls, and is the largest study of allergic disease to date, showing significant overlap in genetic susceptibility between diseases highlighting common origins, particularly in immune function genes

3. B cell development, activation, and differentiation is an ordered and regulated process. Which of the following statements is incorrect? a. B cell development occurs in the bone marrow. b. B cell antibody somatic mutation occurs during the process of immunoglobulin gene rearrangement. c. Receptor editing allows an immature B cell with auto-reactivity to potentially escape cell death in the bone marrow. d. B cells can present antigen to T cells because they capture antigen through their B cell receptor, triggering antigen internalization, processing, and reexpression on major histocompatibility complex molecules. e. Membrane immunoglobulin requires other molecules to signal B cells to become activated.

3. Answer: b. A, C, D, and E are all true statements. B is the untrue statement as the somatic hypermutation process is an antigendependent event that occurs in secondary lymphoid tissues.

3. IgE antibodies affect antiviral immune responses in which of the following ways? a. IgE, bound to viruses, activates complement, leading to opsonization for phagocytosis by macrophages. b. IgE, signaling via FceRI, suppresses the production of type I interferons by plasmacytoid dendritic cells. c. IgE antibodies bound to viral coat proteins prevents viral binding to target cells. d. IgE-mediated mast cell activation induces the production of peptides that disrupt the viral coat proteins.

3. Answer: b. IgE antibodies do not fix complement and there is no evidence that they prevent viral binding to targets or that mast cell factors affect viral integrity.

3. Which of the following lipid mediators has been shown to have antiinflammatory effects? a. Prostaglandin D2 b. Resolvin E2 c. Eoxin C4 d. 8-Isoprostane

3. Answer: b. Resolvins have antiinflammatory effects, whereas the other lipid mediators listed are proinflammatory

3. Which of the following is true regarding mast cell (MC) mediator release? a. MC mediator release is all-or-nothing. b. MC mediator release may be strictly localized to points of cellcell contact. c. The mechanisms of piecemeal degranulation are well defined. d. After IgE-dependent activation, release of lipid mediators derived from arachidonic acid (e.g., LTC4, PGD2) precedes degranulation. e. Orai3 is the ion channel primarily responsible for mediating IgE-dependent Ca2+ influx.

3. Answer: b. See reference 113. A: There is a wealth of evidence that mediator release is highly selective depending on the stimulus, with differential release of granule mediators, lipid mediators, and cytokines. C: Very little is known about the mechanisms of piecemeal degranulation. D: Degranulation occurs first. E: Orai is primarily responsible.

3. Dendritic cells are drug targets for allergic inflammation because: a. They are short lived. b. They take up drugs avidly. c. They control effector cell influx in tissues. d. They metabolize drugs

3. Answer: c. If you can block DC function during the effector response, this greatly reduces activation of effector cells. It is true that DCs are short lived, but this has nothing to do with DCs being drug targets. There is little knowledge on the drug uptake and metabolization by DCs.

3. Generation of cyclic adenosine monophosphate (cAMP) affects airway smooth muscle (ASM) by altering all of the following except: a. Proliferation b. Contraction c. Growth factor receptor expression d. Inflammatory mediator release e. Adhesion molecule expression

3. Answer: c. cAMP has been shown to modulate proliferation of ASM, canonically is known to attenuate contraction of ASM, has been shown to attenuate inflammatory mediator release, and modulates adhesion molecule expression for interaction between ASM and immune cells.

3. Leukocyte adhesion deficiency (LAD)-I is associated with which of the following features? a. Genetic defect in β1 integrin b. Blood neutropenia c. Delayed separation of umbilical cord d. Asthma

3. Answer: c. β1 integrin adhesion molecules mediate separation of the umbilical cord. Genetic defect in β2 integrin mediates LAD-1. Blood neutrophilia is present, because neutrophils cannot migrate from blood to tissues. Asthma is not associated with LAD-1.

3. Which of the following cells is essential for allergen-specific immune tolerance? a. Macrophage b. Eosinophil c. Epithelial cell d. T regulatory cell e. None of the above

3. Answer: d.

3. The cysteinyl leukotrienes signal through the following three G-protein-coupled receptors: a. BLT1, BLT2, and CysLT3/GPR99 b. EP1, EP2, and EP3 c. DP1, DP2, and CysLT1R d. CysLT1, CysLT2, and CysLT3/GPR99

3. Answer: d. Cysteinyl leukotrienes can signal through CysLT1, CysLT2, and CysLT3/GPR99.

3. What has systems biology helped to discover? a. Genetic variants that contribute to disease risk b. Transcriptomic changes and regulatory mechanisms of disease c. Potential allergy biomarkers d. All of the above

3. Answer: d. Examples of each are described in this chapter

3. RNA interference is: a. A process initiated by a large interfering RNA. b. A reverse genetics tool to clarify intracellular signaling pathways. c. A highly conserved molecular mechanism used by prokaryotic organisms. d. A mechanism of gene silencing by double-stranded RNA.

3. Answer: d. RNA interference is a process initiated by a short (small) interfering RNA (siRNA). It is used by eukaryotic organisms. It is a technology to clarify gene functions, does not study signaling pathways.

3. Dust mite avoidance measures in the home have been shown to be effective for which of the following? a. Preventing the development of asthma b. Curing asthma c. Preventing primary sensitization d. Modifying severity of disease during secondary exposure

3. Answer: d. The best established effect of avoidance in the home of a patient is to decrease symptom severity in patients who are already sensitized.

3. Which family of T cells return to and then remain in the tissue for prolonged periods after antigen exposure, are mainly CD8+ , and express high levels of CD69, CD44 and CD103 with absent CCR7 and S1PR1? a. Th9 b. Th22 c. TFH d. TRM

3. Answer: d. The cell surface markers expressed by TRM cells allow them to respond rapidly to pathogen reexposure, and their lack of CCR7 and S1PR1 expression prevents these cells from migrating away from the tissue.

3. Intrinsic abnormalities exist in the airway epithelium of subjects with chronic respiratory disease, including asthma. Which of the following abnormalities are not observed in airway epithelial cells of asthmatics? a. Decreased expression of cytokeratin-19 b. Increased expression of the transcription factor p63 c. Impaired type I interferon responses d. Decreased epidermal growth factor receptor expression

3. Answer: d. The epithelium from asthmatics has many features that suggest a dedifferentiated phenotype, including decreased expression of cytokeratin-19, increased expression of cytokeratin 5/14, increased number of p63-containing basal cells, impaired type I interferon responses, and an increased expression of epidermal growth factor receptor.

3. Gain-of-function mutations in which chemokine receptor causes WHIM syndrome? a. CCR2 b. CCR8 c. CCR10 d. CXCR2 e. CXCR4

3. Answer: e. CXCR4 is required for bone marrow retention and a gain of function mutation in this gene leads to WHIM syndrome.

3. Once differentiated, which specific T cell subset is fixed with regard to its phenotype and function? a. Th1 b. Th2 c. Th9 d. Treg e. None of the above

3. Answer: e. Emerging evidence shows that none of the above differentiated Th cell types has a fixed phenotype and each is susceptible to modulation by the microenvironment that can induce transcription factors and cytokines expressed by a different Th subset.

4. Which of the following statements about ingested allergens is incorrect? a. The beta-parvalbumins are important allergens in cartilaginous fish species muscle tissue. b. The casein proteins in bovine milk represent a significant group of major allergens. c. Tropomyosins present in crustacean and mollusk species are associated with arthropod-shellfish cross-reactivity syndromes. d. Because of their ubiquity in most allergen sources, profilins are referred to as pan-allergens.

4. Answer: a. Cartilaginous fish contain alpha- but not beta-parvalbumin as found in bony fish. For reasons unknown, the alpha-parvalbumins do not appear to be allergenic in humans.

4. Leukocyte adhesion deficiency (LAD)-II is due to a defect in metabolism of which of the following molecules? a. Fucose b. Glucose c. Sucrose d. Lactose

4. Answer: a. LAD-II is associated with a generalized defect in fucose metabolism resulting from a defect in a Golgi-associated guanosine diphosphate-fucose transporter protein.

4. Which of the following lymphocytes can develop into memory cells after activation? a. Innate lymphoid cells b. CD4+ T cells c. Gamma delta T cells d. CD8+ T cells e. B cells

4. Answer: b, d and e. Among the cell types listed, T and B cells, which comprise the adaptive immune system, can develop into memory cells.

4. Which chemokine receptor is critical for lymph node homing of dendritic cells and T cells? a. CCR2 b. CCR7 c. CCR9 d. CXCR1 e. CX3CR1

4. Answer: b. CCR7 promotes homing towards its ligands CCL19 and CCL21, which are produced by lymphatic endothelium and lymph node fibroblasts. CXCR1 and CCR2 promote migration to inflammatory sites, CCR9 promotes gut homing, and CX3CR1 is associated with homeostatic migration of monocyte subsets.

4. What is a key driver gene? a. Gene that significantly changes between two conditions b. Gene that regulates a significant proportion of genes in a given state c. Membrane receptor gene activity in a given state d. Transcription factor

4. Answer: b. Key driver genes are genes that regulate a significant proportion of genes in a given state. Genes that change between two conditions would be differentially expressed genes.

4. Which is a bacterial metabolic by-product with antiinflammatory properties linked to dietary fiber breakdown in the intestine? a. Long chain fatty acids b. Butyrate c. Alpha ketoglutarate d. Citric acid

4. Answer: b. Short chain fatty acids (SCFAs) such as butyrate, propionate, and acetate are generated by microbial breakdown of dietary fiber and have antiinflammatory properties, inducing IL-10 generation from colonic T regulatory cells through activation of the free fatty acid receptor 2, G protein-coupled receptor 43.

4. Which cytokine is involved in promoting fibrosis and remodeling and can also under different circumstances be variably involved in Treg, Th17, Th9, and Th22 differentiation? a. NGF b. TGF-β c. TSLP d. VEGF

4. Answer: b. TGF-β, depending on the context, can function as an antiinflammatory, inflammatory, or remodeling/fibrotic cytokine. It is the coexpression of other factors that determine how it will be used.

4. The presence of a dog in the home has been associated with: a. Increased risk of sensitization to bacterial allergens b. Altered microbiome in floor dust from the home c. Decreased lung function with increased nonspecific bronchial hyperactivity d. Increased risk of lung infection with organisms from the dog

4. Answer: b. The presence of a dog in the home has been shown to consistently alter the microbiome of dust in the house.

4. Which chemokine receptor is involved in the recruitment of Th2 cells? a. CCR2 b. CCR3 c. CCR4 d. CCR5

4. Answer: c. CCR4 is expressed on Th2 cells and is activated by CCL17 (TARC) secreted from activated dendritic cells in allergic inflammation.

4. Which group of cytokines describe suppressor cytokines? a. IFN-γ and IL-12 b. IL-4, IL-5, and IL-13 c. IL-17 and IL-22 d. IL-10 and TGF-β

4. Answer: d.

4. Which one of the following changes is not an epigenetic change? a. DNA methylation b. Histone acetylation c. Histone methylation d. DNA sequence polymorphism e. Histone

4. Answer: d. Epigenetic changes are heritable alterations to the DNA, or the chromatin in which DNA is packaged, that do not affect the DNA sequence.

4. Which cytokines are involved in the development of immune tolerance to a specific antigen? a. IL-10 and IL-17 b. IL-4 and IL-13 c. TNF-α and TGF-β d. IL-10 and TGF-β e. IFN-α and TNF-α

4. Answer: d. IL-10 and TGF-β are secreted by Tregs and suppress T cell effector functions. IL-4 and IL-13 mediate Th2 responses; IL-17, TNF, and IFN mediate inflammatory responses.

4. Which cytokine activates innate lymphoid cell (ILC) 2s? a. Interleukin (IL)-6 b. IL-12 c. IL-21 d. IL-33

4. Answer: d. IL-33, IL-25, and thymic stromal lymphopoietin (TSLP) induce a distinct phenotype and activation profile in human ILC2s. TSLP is important for ILC2 survival, whereas ILC2 activation is more dependent on IL-33, especially when in combination with IL-2 or TSLP. Activation of ILC2s by IL-33 and TSLP dramatically upregulated their surface expression of c-Kit and downregulated expression of the canonical markers IL-7Rα and CRTH2

4. Experimental evidence shows that an acute allergic reaction in the airways can alter neural function by: a. Releasing mediators that activate sensory nerve endings leading to sneezing, coughing, parasympathetic reflex bronchoconstriction and mucus secretion. b. Stimulating mast cells juxtaposed to airway parasympathetic ganglia leading to increases in synaptic neurotransmission. c. Causing an increase in acetylcholine release with each nerve impulse in postganglionic parasympathetic nerve terminals innervating bronchial smooth muscle and thus an enhanced bronchoconstrictor response. d. Causing the release of neurotrophic factors that induce phenotypic changes in vagal sensory neurons. e. All of the above.

4. Answer: e. Acute allergen challenge can evoke sneezing and coughing as well as alter neural control of airway function at all levels of the afferent-CNS-efferent pathways.

4. Fungi of which genera contain outdoor aeroallergens that can be important causes of respiratory allergies in sensitized patients: a. Alternaria b. Cladosporium c. Penicillium d. Aspergillus e. All of the above

4. Answer: e. Each of these geni can generate spores that cause respiratory allergies.

4. Dendritic cells will induce Th2 immune responses when: a They communicate with basophils. b They express interferon regulatory factor (IRF) 4. c They fail to produce interleukin 12 (IL-12). e. All of the above. f. None of the above.

4. Answer: e. IRF4 expressing DCs communicate extensively with other innate cells like basophils. The function of the basophils and other innate immune cells is to stimulate DC activation, but at the same time suppressing IL-12 production.

4. Airway smooth muscle growth is driven primarily by the following pathways: a. PI3K p110 α,β b. PI3K p110 δ c. MAPK/ERK d. Both a and b e. Both a and c

4. Answer: e. Multiple studies have demonstrated that the alpha and beta isoforms of PI3K and MAPK/ERK signaling pathways drive ASM growth. The PI3K delta isoform has been shown to be associated with contractile responses in ASM.

4. Which of the following is true of mast cells in chronic nonallergic (nonatopic) asthma? a. Mast cells (MCs) are not involved. b. MC FcεRI expression is similar to that in nonatopic healthy controls. c. MC type-2 cytokine expression is similar to that in nonatopic healthy controls. d. MCs do not infiltrate the airway smooth muscle (ASM) bundles. e. In severe nonallergic asthma, MC proteases are elevated in sputum and bronchoalveolar lavage fluid, indicative of ongoing MC activation.

4. Answer: e. See reference 204. B: MC FcεRI expression is markedly increased. C: MC type-2 cytokine expression is markedly increased. D: ASM infiltration by MCs is a feature of both atopic and nonatopic asthma phenotypes (see reference 239).

5. Fungal spores can be a very diverse source of aeroallergens. Which of the following statements are true? a. Exposure to Penicillium spores can be high in homes that are damp, and this can be a risk factor for asthma. b. Alternaria is a fungus associated with grass and cropland sources and produces large numbers of club-shaped spores that are 20 to 60 µm in length and 9 to 18 µm wide. c. Aspergillus and Penicillium originate from different families and do not share allergen components. d. Alternaria and Cladosporium mold are the two most common fungal aeroallergen sources.

5. Answer: a, b and d. The level of mold spores present in the air depends on humidity and wind speed but not proximity to sources of decaying plant matter. The sources of mold spores as well as factors affecting release and transport influence concentrations of mold spores.

5. Which of the following is true regarding mast cell (MC) interactions with the immune system? a. MCs are capable of presenting antigen to T cells. b. MCs are not capable of stimulating B cells to produce IgE. c. MC exosomes inhibit dendritic cell development. d. MC-derived histamine and PGD2 increase dendritic cell IL-12 production. e. MCs inhibit T cell Th2 differentiation.

5. Answer: a. Evidence in both rodents and humans. B: Strong evidence that human MCs induce B cell IgE synthesis. C: MC exosomes stimulate the differentiation of immature dendritic cells. D: MC-derived histamine and PGD2 decrease IL-12 production, promoting the development of Th2-promoting dendritic cells. E: MCs promote T cell Th2 differentiation, directly through the production of IL-4 (rodent data) and indirectly through skewing dendritic cells towards a Th2-promoting phenotype.

5. Which of the following statements concerning allergens with protease activity is correct? a. Group 1 from Dermatophagoides farinae has cysteine protease activity. b. Group 2 from Alternaria alternata has metalloprotease activity. c. Group 11 from Aspergillus fumigatus has serine peptidase activity. d. Group 2 from Blatella germanica has aspartic protease activity.

5. Answer: a. The Group 1 allergen from clinically important mite species such as D. farinae is a cysteine protease that belongs to the CA Clan (MEROPS database), which describes proteases with a structure similar to that of papain.

5. Leukocyte adhesion deficiency (LAD)-III patients have which of the following clinical or laboratory features? a. Reduced expression of CD18 b. Tendency for bleeding c. Reduced expression of CD15s d. Normal inside out integrin signaling

5. Answer: b. Tendency for bleeding is related to several integrins (β1, β2, β3) expressed by leukocytes and importantly also platelets being defective, resulting in defective signaling in platelets with resultant easy bleeding. There is normal expression of CD18 and CD15s, and defective inside out integrin signaling.

5. Air conditioning of a house can: a. Decrease cockroach growth because of decreased humidity b. Increase indoor air exchange because of air entry through specific air entry sites c. Remove one or more gallons of water per day from a house d. Decrease airborne cat allergen because of air filtration in the system

5. Answer: c. Air conditioning is an effective method of removing water from a house; this does not affect cockroach growth, but it can decrease mite growth.

5. Which cell is responsible for the production of blocking IgG4 antibodies? a. Macrophage b. Eosinophil c. Epithelial cell d. B regulatory cell e. None of the above

5. Answer: d.

5. For which cytokine is there evidence that it might induce steroid resistance in patients with asthma? a. Interleukin (IL)-25 b. IL-33 c. Transforming growth factor (TGF)-β d. Thymic stromal lymphopoietin (TSLP)

5. Answer: d. TSLP-induced corticosteroid resistance of mouse and human innate lymphoid cell (ILC) 2s suggests that corticosteroids, which are used as a mainstay of treatment for allergic diseases, may not reduce ILC2 responses driven by TSLP.

5. What pair of chemokine receptors participate in the trafficking of CD4+ Th1 and Th2 cells, respectively? a. CCR1 and CCR2 b. CCR3 and CXCR6 c. CCR4 and CCR8 d. CXCR1 and CCR5 e. CXCR3 and CCR4

5. Answer: e. CXCR3 is associated with Th1 cell migration while CCR4 and CCR8 are both associated with Th2 cell migration

5. Release of inflammatory mediators by airway smooth muscle (ASM) is attenuated by: a. Cyclic adenosine monophosphate generating agents b. Vitamin D c. Glucocorticoids d. Bronchial thermoplasty e. All of the above

5. Answer: e. Each of the answers has been demonstrated to decrease inflammatory mediator release from ASM either through attenuating signaling pathways associated with mediator release or, in the case of thermoplasty, physically decreasing the release of inflammatory mediators through killing the ASM itself.

6. Allergen exposure of children in school: a. Can contribute to asthma symptoms in schools b. Can induce tolerance to cat or mouse allergens c. Has been shown to be increased by dog allergen carried in on children's clothing d. Is a common cause of primary sensitization

6. Answer: a. Allergens from mice in the school or cat allergens carried in on children's clothing have been shown to contribute to asthma symptoms of children in the school.