FIT Corner Notes Flashcards
Glucocorticoids have which of the following effects on eosinophils?
a. Decrease eosinophil chemotaxis
b. Decrease eosinophil degranulation
c. Prevent an increase in blood eosinophil progenitors after antigen challenge
d. Acutely increase circulating eosinophil numbers
C. GCs have been shown to 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.
Inhibitors targeted at which enzyme have been able to restore glucocorticoid sensitivity in patients with steroid refractory asthma?
a. P38 MAPK (MAPK14)
b. DNase I
c. HDAC6
d. IκB kinase
A. P38 MAPK
IL-2, IL-4, and IL-13 can induce glucocorticoid receptor (GR) phosphorylation under the MAPK14 pathway although the precise mechanisms that result in enhanced activation or increased expression of MAPK14 in the airways of refractory asthma are unclear.
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.
A patient with asthma-COPD overlap syndrome presents to your clinic. He is unwilling to stop smoking, and his lung disease has been difficult to control with ICS/LABA therapy and inhaled tiotropium. He asks what other medications he might try. The bronchodilator theophylline has been used to restore the activity of which enzyme (and thus glucocorticoid sensitivity) in COPD patients and in smoking asthmatic patients in whom the activity of this enzyme is reduced?
a. Histone deacetylase 2 (HDAC2)
b. Interferon-regulatory factor-1 (IRF)
c. Mitogen-activated protein kinase (MAPK)
d. NF-κB
A. HDAC2.
Reactive oxygen species have been shown to increase glucocorticoid resistance, both directly and indirectly. In patients who smoke, increased formation of peroxynitrite (another ROS) leads to enzymatic inactivation of HDAC2 which is usually enhanced by GR-α activity. 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.
The 5-lipoxygenase pathway is most abundant in which cell type:
a. Epithelial
b. Myeloid
c. Smooth muscle
d. Lymphoid
B. Myeloid
Which of the following statements is true about the two cysteinyl leukotriene receptors, CysLT1 and CysLT2?
a. Leukotriene receptor antagonists block both receptors equally.
b. CysLT1 and CysLT2 have been mapped to airway smooth muscle cells.
c. Only CysLT1 is found on mast cells.
d. Both are receptors for leukotriene B4.
b. CysLT1 and CysLT2 have been mapped to airway smooth muscle cells.
Both CysLT2 and CysLT1 have been mapped to airway smooth muscle. LTRAs only antagonize CysLT1. Both receptors are found on mast cells. LTB4 has its own receptors (BLT1 and BLT2).
Leukotriene receptor antagonists are able to prevent which of the following after allergen challenge:
a. Immediate and late response
b. Immediate response only
c. Eosinophil number in the late response
d. Mucus production
a. Immediate and late response
Zafirlukast given prior to allergen challenge inhibited the immediate response by 80% and the late response by 50%. It has no effect on eosinophil number after challenge or mucus production. It does decrease the cellular influx of basophils and lymphocytes.
What effect do antileukotriene drugs have on FEV1?
a. No effect
b. Small effect but not until 24 hours after ingestion
c. Small but immediate effect
d. Same effect as beta agonists and should be used in acute asthma exacerbations
c. Small but immediate effect
Oral and IV preparations have an immediate bronchodilator effect of 10-30% improvement in FEV1. IV is more potent and rapid than oral. Antileukotrienes are synergistic with beta agonists but are not sufficient to treat acute asthma attacks and not recommended in that
setting.
Which of the following is NOT a correct integrin-ligand pairing?
a. LFA-1:ICAM-1
b. VLA-4:ICAM-2
c. MAC-1:ICAM-1
d. LFA-1:ICAM-2
b. VLA-4:ICAM-2
- LFA-1 binds to ICAM-1, ICAM-2, and ICAM-3.
- MAC-1 binds to ICAM-1.
- VLA-4 DOES NOT bind to ICAM-2.
- VLA-4 binds to VCAM-1.
TNF can cause all of the following EXCEPT:
a. Inhibit myocardial contractility
b. Intravascular thrombosis
c. Cachexia
d. Elevated CRP
D. 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 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.
Type 1 interferons (IFN-α and IFN-β) are important for protection against viral infections, they act through which of the following mechanisms?
a. Sequestration of lymphocytes in lymph nodes
b. Upregulating class II MHC molecules
c. Promote naïve T cell differentiation to Th17 cells
d. Stimulating adaptive immune response via two-signal hypothesis
A. Sequestration of lymphocytes in lymph nodes. Type 1 interferons protect against viral infections by sequestering lymphocytes in lymph nodes, increasing cytotoxicity of NK cells, upregulating class I MHC molecules (increasing probability that virally infected cells will be killed by CD8 cells), and promoting differentiation of naïve T cells to Th1 cells.
What is the strength of the binding between a single combining site of an antibody and epitope of an antigen called? a. Avidity b. Affinity c. Diversity d. Affinity maturation
B. Affinity
The strength of the binding between a single combining site of an antibody and an epitope of an antigen is the affinity of the antibody. The affinity is represented by the dissociation constant (kD), which indicated how easy it is to separate an antigen-antibody complex into its constituents. A smaller kD indicates a stronger or higher affinity interaction because a lower concentration of an antigen and of antibody is required for complex formation. Avidity is the overall strength of an attachment that takes into account binding of all sites to all available epitopes.
The hinge region of an immunoglobulin
a. Is located between the CH2 and CH3 domains
b. Is located between the CH1 and CH2 domains
c. Allows for rigidity in the antibody structure
d. Allows for rotation between the CH2 and CH3 domains
B. Is located between CH1 and CH2 domains
In a patient with lung disease, an elevated DLCO indicates which of following disease states?
a. COPD
b. Interstitial Lung Disease
c. Uncontrolled asthma
d. Well controlled asthma
C. Uncontrolled Asthma
In patients with asthma the DLCO is either normal or elevated. If the DLCO is elevated that indicates that the asthma is uncontrolled. The DLCO would be decreased in COPD and interstitial lung disease.
Bronchial challenges are useful tests for the evaluation of asthma. Tests can be performed with direct acting constrictors or indirect-acting constrictors. Which of the following is an example of an indirect-acting constrictor?
a. Histamine
b. Methacholine
c. Albuterol
d. Mannitol
D. Mannitol
Both methacholine and histamine are considered direct-acting constrictors in bronchial challenges. Indirect acting constrictors include mannitol, adenosine, exercise, and cold air.
The Wisconsin Childhood Origins of Asthma (COAST) study found that wheezing in the first year of life associated with a particular virus is the strongest predictor of wheezing in the third year of life. Which of the following is that virus? A. Human rhinovirus (HRV) B. Influenza C. RSV D. Enterovirus
A. Human rhinovirus (HRV)
The COAST study prospectively evaluated timing, frequency, severity and cause of symptomatic viral
infection in the first 3 years of life in relation to later wheezing illness in a cohort of 289 neonates at high familial risk for asthma. This study highlighted the prognostic importance of HRV. Having one or more HRV-associated wheezing episodes during the first year of life was more strongly associated with wheezing in the third year than having one or more RSV-associated wheezing episodes in the first three years of life. Also, first-year wheezing associated with HRV was the strongest predictor for third-year wheeze.
