FIT Corner Quiz Flashcards

1
Q

What abnormalities of the arachidonic acid pathway are seen in patients with AERD?

A

Decreased prostaglandin E2 (PGE2 is anti-inflammatory), overproduction of leukotrienes, and increased production of lipoxin A4.

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2
Q

What allele has been identified as a genetic marker for AERD in Polish and Korean populations?

A

HLA DPB1*0301

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3
Q

What is the usual order of AERD symptom development?

A

Rhinosinusitis with polyps, asthma, aspirin hypersensitivity

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4
Q

Which dose of aspirin is recommended to maintain cross-desensitization to any dose of all NSAIDs?

A

325 mg

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5
Q

What is considered the gold-standard test for the diagnosis of IgE-mediated food allergy?

A

Double-blinded, placebo-controlled oral food challenge

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6
Q

What is the false-positive rate of open food challenges?

A

30%

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7
Q

What is the estimated false-positive rate in double-blinded placebo-controlled food challenges (DBPCFC)?

A

1%

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8
Q

In what circumstances should an OFC be postponed?

A

Asthma exacerbation within 1 week of the challenge, atopic dermatitis flare on challenge day

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9
Q

What is the recommended time interval between doses during an OFC?

A

10-20 minutes

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10
Q

What is an example of food allergens in unexpected and non-food items likely to pose a low risk for adverse reactions in patients with food allergies?

A

Shrimp or crustacean shell derivatives found in glucosamine-chondroitin supplements or chitosan or chitin products

It is possible for patients with food allergies to develop contact urticaria or dermatitis with exposure to almond or milk in shampoos or ointments. In regards to pet foods, fish food on fingers may result in the transfer of protein to the eyes or mouth resulting in symptoms. Additionally, animal lick may cause contact urticaria. For food allergens in medications such as the lactose in dry powder inhalers, there have been case reports of reactions to casein identified in dry powder inhalers. The relevance to milk in pills or pharmaceutical grade lactose is unclear.

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11
Q

What foods account for most episodes leading to fatalities?

A

peanut, tree nuts, fish, shellfish and milk

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12
Q

Dual-allergen exposure hypothesis

A

Allergic sensitization to food can occur through low-dose cutaneous exposure and that early consumption of food protein induces tolerance

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13
Q

Airway inflammation in asthma is a multicellular process. What cells are involved in this process?

A

eosinophils, CD4+ T cells, mast cells, and neutrophils

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14
Q

Which cells are involved in the upregulation of TGF-beta to increase smooth muscle contractility?

A

Mast cells

They affect airway smooth muscle contractility directly and indirectly by upregulation of airway smooth muscle TGF-beta which transforms smooth muscle into a more contractile phenotype.

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15
Q

Which cytokine modulates eosinophilic production, maturation, activation, and survival in blood?

A

IL-5

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16
Q

Which cytokine uniquely promotes airway mastocytosis and mast cell progenitor development and localization to the airway?

A

IL-9

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17
Q

What is the principal Th1 effector cytokine?

A

IFN-γ

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18
Q

Which family of cytokines are linked to autoimmune diseases including RA, IBD, and MS, in addition to increased expression in asthmatic patients?

A

IL-17 family cytokines

The IL-17 family cytokines, IL-17A to IL-17F, are linked with several autoimmune diseases. IL-17E and IL17F are of interest in asthma because their expression is increased in the airways of asthmatic patients, and levels have been correlated with disease severity.

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19
Q

In which cell type is the 5-lipoxygenase pathway most abundant?

A

Myeloid cells

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20
Q

What receptor(s) do LTRAs block?

A

LTRAs only antagonize CysLT1

Key Fact: Both CysLT1 and CysLT2 receptors are found on mast cells

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21
Q

What does Zileuton block?

A

Blocks 5-LO ⇒ Blocking the production of LTB4 as well as LTC4

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22
Q

LTB4 function

A
  1. Chemoattractant for neutrophils and eosinophils
  2. Activation of neutrophils
  3. Sensitization to allergen

* No bronchoconstriction

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23
Q

In general, when a school-age child requires an asthma controller medication for mild persistent asthma, what is the appropriate order for a trial of medications?

A

Trial of low-dose ICS and, if no improvement, trial of LTRA, either as add on or replacement

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24
Q

In the absence of a spacer device, what percentage of inhaled corticosteroid delivered by an MDI or DPI is delivered to the lungs?

A

10-20%

The use of a spacer and mouth rinsing after inhaler use can reduce oral deposition by 90%.

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25
Q

What is a feature of an inhaled corticosteroid with a good therapeutic index?

(7 characteristics)

A
  1. Low oral bioavailability
  2. Small particle size
  3. Rapid metabolism
  4. High clearance
  5. High plasma protein binding
  6. Low systemic half-life. When designing inhaled
  7. Lipophilicity (increases pulmonary tissue retention)
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26
Q

What effects do GCs have on eosinophils?

A

GCs → acute reduction in circulating basophils, eosinophils, and monocytes with numbers returning to baseline 24-48 h after a single dose.

Effects on eosinophils: Prevent eosinophil migration to the lung and prevent the increase in blood eosinophil progenitors after antigen challenge.

*GCs do not modulate eosinophil chemotaxis, adhesion, or degranulation.

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27
Q

Inhibitors targeted at which enzyme have been able to restore glucocorticoid sensitivity in patients with steroid-refractory asthma?

A

P38 MAPK (MAPK14)

Phosphorylation of GR in a specific location induced by pro-inflammatory insults and mediated by the MAPK14 pathway leads to a conformational change in GR which downregulates GR responses. Patients with severe asthma have inappropriate overexpression of MAPK14 compared to patients with non-severe asthma, and MAPK inhibitors have been shown to restore glucocorticoid sensitivity in some of these patients.

28
Q

Which IL, associated with neutrophilic asthma, is elevated in sputum and serum samples from patients with severe asthma and has been shown experimentally to inhibit corticosteroid responsiveness in human bronchial epithelial cells?

A

IL-17 (sputum IL-17 levels correlate with sputum neutrophilia.)

Neutrophilic asthma, a subset of corticosteroid-refractory asthma, is associated with the presence of IL-17 and Th17 cells. This chemokine enhances the production of profibrotic cytokines and extracellular matrix proteins.

29
Q

Supplementation of which vitamin may augment responsiveness to glucocorticoids in patients with steroid-refractory asthma by increasing steroid-induced T cell secretion of IL-10?

A

Vitamin D3 (calcitriol)

Vitamin D3 has been shown to increase the secretion of IL-10 from Treg cells isolated from patients with steroid-refractory asthma to comparable levels in patients with non-severe asthma who were treated with Dexamethasone alone.

30
Q

The bronchodilator theophylline has been used to restore the activity of which enzyme (and thus glucocorticoid sensitivity) in _COPD patients and in smoking asthmatic patient_s in whom the activity of this enzyme is reduced?

A

Histone deacetylase 2 (HDAC2)

HDAC2 is important in the GR-mediated repression of inflammatory genes including GM-CSF and CXCL8. Theophylline has been shown to increase HDAC2 activity in cells and thus restore glucocorticoid effects.

31
Q

Integrin-ligand pairing

A
  • LFA-1 binds to ICAM-1, ICAM-2, and ICAM-3.
  • MAC-1 binds to ICAM-1.
  • VLA-4 binds to VCAM-1.
32
Q

Chemokine and their original name

A
  • CCL17 is TARC
  • CCL11 is eotaxin
  • CCL5 is rantes
  • XCL1 is lymphotactin
33
Q

What is the defect in type 1 leukocyte adhesion deficiency?

A

Type 1 leukocyte adhesion disorder is due to an inability to encode the beta subunit of LFA-1 and MAC-1. It is an autosomal recessive inherited deficiency in the CD18 gene.

34
Q

What is the defect in type 2 leukocyte adhesion deficiency?

A

Type 2 leukocyte adhesion deficiency is due to the lack of the Golgi GDP-fructose transporter needed to express the carbohydrate ligands for E-selectin and P-selectin.

35
Q

How does the sphingosine 1-phosphate (S1P) gradient drive T-cells from the blood into the lymph nodes?

A

S1PR1 stimulates the migration of cells towards a gradient of S1P. Circulating naïve T cells have very little surface S1PR1 because the high blood concentration of S1P causes internalization of the receptor. After a naïve T cell enters a lymph node, where S1P concentrations are low, S1PR1 reappears on the cell surface over a period of several days.

36
Q

If a naïve T cell is activated by antigen in the lymph node, which protein helps the activated naïve T-cell to remain in the lymph node?

A

CD69

CD69 is a protein that binds S1PR1 and reduces its cell surface expression. This prevents the naïve T cell from migrating from the low concentration of S1P in the lymph node to the high concentration of S1P in the blood.

37
Q

Which chemokine receptor is important for B cells to migrate into the white pulp of the spleen?

A

CXCR5

CXCR5 promotes the movement of B cells into the white pulp in response to a chemokine called CXCL13

38
Q

What do bone marrow-homing IgG-secreting plasma cells express?

A

VLA-4 and CXCR4, which bind respectively to VCAM-1 and CXCL12 expressed on bone marrow sinusoidal endothelial cells.

39
Q

Which chemokine receptor plays a critical role in dendritic cell migration into the lymph nodes and is expressed at high levels on naïve T-cells to promote their interaction?

A

CCR7

CCR7 is expressed at high levels on naïve T cells. Chemokines CCL19 and CCL21 interaction with CCR7 ensures that naïve T cells increase integrin avidity and are able to adhere firmly to HEVs. Shared expression of CCR7 between naïve T cells and dendritic cells maximizes the chances of the two cells interacting.

40
Q

What are the cellular membrane TLRs?

A

The cellular membrane TLRs are 1, 2, 4, 5, 6

41
Q

Genetic deficiency in UNC-93B results in susceptibility to which infectious disease?

A

HSV encephalitis

UNC-93B is a protein on the endoplasmic reticulum required for endosomal localization and proper function of TLR 3, 7, 8, and 9. Endosomal TLRs recognize dsRNA (TLR3), ssRNA (TLR7), and unmethylated CpG motifs in DNA (TLR9). The endosomal location of ssRNA and dsRNA reflects microbial origin.

The mutation in UNC-93B reflects the importance of the endosomal location of TLRs for innate defense against viruses.

42
Q

Which membrane TLR does not exclusively signal via myD88 to the transcription factor NF-kB?

A

TLR4

TLR4 can signal via myD88 to NF-kB or via the adaptor protein TRIF to activate IRF3 and IRF7 transcription factors. IRF3 and IRF7 promote the induction of type 1 interferons (IFN-α and IFN-β) which are important for antiviral responses. The NF-kB pathway encodes molecules required for inflammatory response including TNF and IL-1 as well as chemokines (CCL2 and CXCL8) as well as endothelial adhesion molecules (E-selectin).

43
Q

What are the cryopyrin-associated periodic syndromes?

What is the underlying mutation?

A

FCAS (cold-induced fever, “urticaria”), Muckle-Wells (fever, “urticaria”, limb pain, deafness), NOMID/CINCA (“urticaria”, epiphyseal overgrowth, chronic meningitis)

CIAS1/NLRP3, which encodes cryopyrin, a key molecule in the inflammasome, characterized by excessive IL-1ß production

Key fact: IL-1 and IL-1R antagonists can be used to treat these disorders as IL-1 is converted from pro-IL-1β in the NLRP3 inflammasome (anakinra and canakinumab).

Key fact: Renal amyloidosis associated with more severe phenotypes

44
Q

Activated neutrophils and macrophages kill phagocytosed microbes using all of the following EXCEPT:

  • Nitric oxide
  • Elastase
  • Reactive oxygen species
  • Granzymes
A

Granzymes

Granzymes are used by NK cells, not macrophages or neutrophils, and are injected into the cytosol of affected cells to induce cell death. Elastases are proteolytic enzymes like granzymes but are used by macrophages and neutrophils.

45
Q

TNF can cause all of the following EXCEPT:

  • Inhibit myocardial contractility
  • Intravascular thrombosis
  • Cachexia
  • Elevated CRP
A

Elevated CRP

TNF may be produced in large quantities in severe infections and can inhibit myocardial contractility and smooth muscle tone resulting in shock. It can also cause intravascular thrombosis by stimulating endothelial cell expression of tissue factor. Prolonged exposure to TNF can result in the wasting of muscle and fat cells from TNF-induced appetite suppression.

Elevation in acute phase reactants such as CRP, SAP, and fibrinogen are due to IL-1 and IL-6, not TNF.

46
Q

Type 1 interferons (IFN-α and IFN-β) are important for protection against viral infections, they act through which mechanisms?

A

Sequestration of lymphocytes in lymph nodes

Type 1 interferons protect against viral infections by sequestering lymphocytes in lymph nodes, increasing the cytotoxicity of NK cells, upregulating class I MHC molecules (increasing probability that virally infected cells will be killed by CD8 cells). Promote differentiation of naïve T cells to Th1 cells.

47
Q

ILC2 cells are important for defense against which microorganisms?

A

Helminthic parasites

ILC2 cells resemble Th2 cells. Their development is dependent on IL-7 (ILC1 cells require IL-7 and IL-15). They are important for defense against helminthic parasites and may contribute to allergic diseases.

ILC3 cells participate in the defense against extracellular fungi.

48
Q

What are complementary determining regions made of?

A

CDR1, CDR2, CDR3

CDR3 generates the most sequence of diversity.

49
Q

Where is the hinge located?

A

Between the CH1 and CH2 domains

The flexibility of the antibody is mainly due to the hinge regions located between the CH1 and CH2 domains, which permit independent movement of antigen-binding sites relative to the rest of the molecule.

50
Q

What does immature B cell produce?

A

Membrane IgM

Immature B cells produce membrane IgM. Mature B cells produce membrane IgM and IgD. Antibody secreting cells produce high rates of IgM, IgG, IgA, or IgE secretion.

51
Q

What are the membrane forms of Ig heavy chain transmembrane regions made up of?

A

The membrane forms of the Ig heavy chains have hydrophilic amino acid residues

Key fact: The cytoplasmic domains differ between the different isotypes

52
Q

Which chromosome contains the MCH locus?

A

Chromosome 6

There are three class I MHC genes called HLA-A, HLA-B, HLA-C, and three class II HLA gene loci called HLA-DP, HLA-DQ, and HLA-DR

53
Q

Mutations in what gene results in X-linked hyper IgM syndrome?

A

CD40L

AID, CD40, and UNG mutations are associated with hyper IgM syndromes type 2, 3, and 5, respectively. These are all autosomal recessive.

54
Q

Where does affinity maturation occur in the lymph node?

A

Germinal center

55
Q

Which type of cellular receptor is an integral membrane protein with intrinsic catalytic enzyme domain(s) in the cytoplasmic tail?

A

Receptor tyrosine kinase

Receptor tyrosine kinases are integral membrane proteins that activate an intrinsic tyrosine kinase domain (or domains) located in the cytoplasmic tails of the receptors when they are cross-linked by multivalent extracellular ligands.

56
Q

Which Syk family tyrosine kinase phosphorylates adaptor proteins such as LAT, an event which is an important part of early T cell activation?

A

ZAP-70

ZAP-70 deficiency: Low CD8 T cells with normal CD4 T and B cells, abnormal response to mitogens (but PMA + ionomycin induce T cell proliferation)

57
Q

Tacrolimus complexes with _____ and inhibits ________, thus blocking NFAT translocation into the nucleus

A

Tacrolimus complexes with FK506-binding protein (FKBP) and inhibits calcineurin, thus blocking NFAT translocation into the nucleus

58
Q

C3d binds this cell surface molecule which forms part of the B cell coreceptor complex

A

CD21 (CR2)

The B cell coreceptor complex is composed of CD21 (CR2), CD19, and CD81. CD21 (CR2) is also known as the type 2 complement receptor and binds C3d when it is complexed with antigen or to an antigen-antibody complex. When C3d complexed to antigen binds CD21 (CR2), several steps occur which lead to enhanced B cell activation.

59
Q

Mutations in SH2D1A, the gene which encodes __________, are the cause of X-linked lymphoproliferative syndrome (XLP)

A

SAP

SH2D1A encodes SLAM-associated protein (SAP) which is an adaptor protein that can associate with proteins that contain immunoreceptor tyrosine-based switch motif (ITSM) which can mediate inhibitory or activating functions. One such protein is 2B4, and defective 2B4 signaling contributes to the immune deficits in patients with XLP.

60
Q

Type II cytokine receptors (interferon receptor family) utilize which signaling pathway?

A

JAK-STAT

All of the type II receptors engage JAK-STAT signaling pathways. Type I cytokine receptors also use the JAK-STAT pathway.

61
Q

IL-18

A

IL-18 and IL-1 are both ligands of the IL-1 receptor family, and both of these cytokines are involved in the activity of the inflammasome. The receptors of this family share a conserved cytosolic sequence called the Toll/IL-1 receptor (TIR) domain and engage similar signal transduction pathways.

62
Q

Gain-of-function mutations in _________ cause myelodysplastic syndrome

A

JAK2

Gain-of-function mutations in JAK2 can cause a myelodysplastic syndrome with varying phenotypes of aplastic anemia and polycythemia vera.

63
Q

Mutations affecting _______ can lead to a form of SCID similar to common γ chain deficiency

A

JAK3

64
Q

Negative mutations in ______can lead to problems with Th17 responses

A

STAT3 can lead to problems with Th17 responses, leading to an immunodeficiency disease

Activating mutations of STAT3 are seen in large granular lymphocytic leukemia

65
Q

What opsonins are the most efficient for promoting phagocytosis?

A

IgG1 and IgG3

66
Q

What is the most common human complement deficiency?

A

C2 deficiency