40 - Eosinophilic Diseases Flashcards
Eosinophils develop in the bone marrow from multipotential, stem cell-derived _____+ myeloid progenitor cells
CD34
Stimulatory cytokines and growth factors for eosinophils
IL-3
GM-CSF
IL-5
Most selective eosinophil-active cytokine, but is relatively late-acting
IL-5
Mature eosinophils are slight (smaller/larger) than neutrophils
Larger
Five highly basic proteins found within the eosinophil’s cystoplasmic granules
Major basic protien-1
Major basic protien-2
Eosinophil-derived neurotoxin/Ribonuclease 2
Eosinophil cationix protien/Ribonuclease 3
Eosinophil peroxidase
Other types of the eosinophil’s cystoplasmic granules
Primary granules
Small granules
Secretory vesicles
Characteristically found in asthmatic sputum and in feces from patients with helminth infections or eosinophilic gastroenteritis
Charcot-Leyden crystal protein or galectin-10
Charcot-Leyden crystal protein can also be found in
Neutrophils
Charcot-Leyden crystal protein is contained in
Primary granules
More common in immature eosinophilic promyelocyes
Primary granules
Contain acid phosphatase and arylsulfatase
Small granules
Also referred to as tubulovesicular structures or microgranules, are characterized by their small, dumbbell-shaped appearance and their albumin content
Secretory vesicles
Most abundant granules in number
Secretory vesicles
Principal stores of arachidonic acid; aso contain the enzymes cyclooxygenase, 5- and 15-lipoxygenase
Lipid bodies
Y/N: Eosinophils are present in blood permanently.
No - transiently, ranging from 8-18 hours
Eosinophils comprise _____% or less of circulating leukocytes
6
Eosinophils are primarily tissue-dwelling cells, with an average life span of
2-5 days; may reach up to 14 days
Only tissues in which eosinophils normally reside
Bone marrow Spleen Lymph node Thymus Gastrointestinal tract from the stomach to the colon, sparing the esophagus
Only organ other than the bine marrow in which extracellular eosinophil granule protein deposition is observed even under homeostatic conditions
Gastrointestinal tract
Eosinophils and their granule proteins are found in the _____ in normal gastrointestinal tract and are not found in _____
Lamina propria
Peyer patches or epithelium
The recruitment of eosinophils to the gastrointestinal, thymic, uterine, and mammary tissues is under the control of
CCL11
Eosinophils can migrate to areas of tissue injury or necrosis through the _____ released from necrotic cells
High-mobility group box-1 protein (HGMB1)
Y/N: Once eosinophils enter tissues, most do not recirculate
Yes
Among the products of eosinophils that are most damaging to the host are the
Cationic proteins (EPO, ECO, EDN, MBP-1)
All 4 of the cationic proteins (EPO, ECP, EDN, MBP-1) likely contribute to the edema observed in skin diseases because of their
Vasodilatory effect
Eosiniphil granule proteins induces direct tissue damage to
Host cellls and microbes
Comprises the crystalloid core of the specific eosinophil granule
Major basic protein
_____, but none of the other eosinophil granule proteins, stimulate histamine and LTC4 release from human basophils
MBP-1 and MBP-2
Key participant in generating reactive oxidants and free radical species in activated eosinophils
Eosinophil peroxidase
Protein that is present in the highest molar concentration in eosinophil granules
MBP
By weight, is the most abundant protein constituting approximatelt 25% of the specific eosinophil granule’s total protein mass
EPO
Play a role in viral host defense to RNA viruses
ECP and EDN
Functions as an alarmin, alerting the adaptive immune system to preferentially enhance antigen-specific Th2 responses
EDN
Y/N: No single surface protein is uniquely expressed in eosinophils
Yes
Most important selectin pair in eosinophil migration into tissues
P-selectin and PSGL-1
Among the nonselective drugs for eosinophil reduction, _____ generally are very effective
Glucocorticoids
Y/N: Glucocorticoids cause an immediate reduction in circulating eosinophils.
Yes - within 3 hours
Mutation in myeloproliferative hypereosinophilic syndrome (chronic eosinophilic leukemia)
FIP1L1-PDGFRA
Approved for the treatment of chronic myelogenous leukemia and hypereosinophilic syndrome
Imatinib mesylate
Monoclonal antibody to CD52; used in the treatment of chronic (B-cell) lymphocytic leukemia and T-cell lymphoma
Alemtuzumab
Eosinophils, but not _____, also express CD52
Neutrophils
First humanized monoclonal antibody against IL-5
Mepolizumab
Anti-IL-5 receptor alpha humanized monoclonal antibody
Benralizumab
Y/N: Pathogenic influence of eosinophils may be unrelated to their numbers in tissues
Yes