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62 Cards in this Set
- Front
- Back
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Who was the first person to describe mast cells? What year?
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Paul Erlich, 1878
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What does MAST mean?
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"feeding"
"fattening" |
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How big are mast cells?
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9-14 um
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What cells are precursors to mast cells? Where do they develop?
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pluripotent CD34+ stem cells,
bone marrow |
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List the 2 mast cell phenotypes.
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1) MCt (tryptase)
2) MCtc (typtase, chymase) |
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Where are MCt cells found?
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respiratory tract and intestinal MUCOSA
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Where are MCtc cells found/
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SUBmucosa of skin, blood vessels, eyes, synovium, intestine, respiratory tract
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The high affinity IgE receptor (tetrameric form) is composed of what subunits?
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alpha chain
gamma chain x2 beta chain |
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What cells express the tetrameric form of the high affinity IgE receptor?
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mast cells, basophils, eosinophils
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What cells express the trimeric form of the high affinity IgE receptor? What chain is absent?
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monocytes
dendritic cells -missing the beta chain |
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What does IgE bind to on the high affinity IgE receptor?
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alpha chain
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What is the signaling subunit of the high affinity IgE receptor?
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gamma chain
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What are the preformed mediators in mast cells?
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histamine, tryptase, chymase, heparin
-responsible for the immediate allergic reaction |
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What are the lipid derived mediators in mast cells?
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PGD2, LTC4, LTB4, PAF
-responsible for the late allergic reaction |
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What form(s) of typtase is/are elevated in systemic mastocytosis?
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alpha and beta tryptase
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What form(s) of tryptase is/are elevated in anaphylaxis?
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beta tryptase (mature)
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What is histamine's effect?
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smooth muscle contraction
mucus production vasodilation gastric acid secretion wakefulness |
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What is typtase's effect?
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protease
endopeptidase |
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What is carboxypeptidase's effect?
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peptidase (c-terminal end of peptide)
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What is prostaglandin D2's effect?
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increase vascular permeability
bronchoconstriction inhibits platelet aggregation chemoattraction |
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What is leukotriene C4/B4's effect?
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increase vascular permeability
bronchoconstriction |
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What is platelet activating factor's effect?
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bronchoconstriction
vasodilation platelet aggregation |
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What are the 3 types of cutaneous mastocytosis?
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1. urticaria pigmentosa
2. diffuse cutaneous mastocytosis 3. mastocytoma of the skin |
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What is Darier's sign?
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urticaria and erythema observed on and around a macule after stroking the lesion
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What are the 8 forms of systemic mastocytosis?
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1. indolent systemic mastocytosis (ism)
2. smoldering sm 3. isolated bone marrow mastocytosis 4. SM-AHNMD 5. Aggressive systemic mastocytosis 6. Mast cell leukemia 7. Mast cell sarcoma 8. Extracutaneous mastocytoma |
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What is the most common activating mutation in mastocytosis?
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ASP 816 VAL (substitute valine for aspartic acid)
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What are the 2 known mechanisms in the pathogenesis of mastocytosis?
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1. activating mutation in c-kit (ASP 816 VAL)
2. inhibition of mast cell apoptosis via constitutive expression of Bcl-XL adn Bcl-2 |
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What markers identify mast cells?
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CD117 (c-kit);
CD2 and/or CD25 |
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What will a bone marrow biopsy show in mastocytosis?
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focal infiltrates of positive spindle-shaped mast cells
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Name triggers that induce hypotension in patients with mastocytosis?
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insect stings
alcohol aspirin narcotics iodinated contrast material |
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T or F:
A patient with severe anaphylaxis following a hymenoptera sting should have a baseline tryptase done to screen for mastocytosis. |
True
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What are the major and minor criteria for the diagnosis of systemic mastocytosis?
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Major:
- biopsy with multifocal, dense infiltrates of mast cells (>15) Minor: ->25% mast cells with spindle shaped or atypical morphology -C-kit mutation at codon 816 -coexpression of CD117 and CD2 and/or CD25 -total serum tryptase >20ng/ml |
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How many major and/or minor criteria do you need for a systemic mastocytosis diagnosis?
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One major and one minor
OR three minor |
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How do you treat systemic mastocytosis?
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antihistamines
H2 antag Disodium cromoglycate Epinephrine Topical steroids Calcium supplementation |
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What variables are associated with a poor prognosis in mastocytosis?
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-male
-absence of cutaneous symptoms -presence of systemic symptoms -anemia/thrombocytopenia -abnormal LFTs -lobated mast cell nuclei -associated heme malignancy -low percentage of fat cells on bone marrow biopsy |
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What are mast cell stabilizer's mechanism of action?
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-inhibits IgE mediated calcium channel activation (necessary for degranulation of mast cells)
-inhibits chloride transport/channels that indirectly lower intracellular calcium levels -blocks eosinophil activation -inhibits mast cell mediator relaease -inhibitis neutrophil activation -inhibits IgE production |
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What is the most common adverse effect of mast cell stabilizers?
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unpleasant taste in mouth
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What is the cytokine important for basophil development? Eosinophil?
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Basophil- IL-3
Eosinophil- IL-5 |
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What are the typical ages of presentation in diffuse cutaneous mastocytosis? and mastocytoma?
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diffuse cutaneous mastocytoma= <3yr
mastocytoma = birth to three months |
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What activates all mast cells?
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substance P
IgE IgG |
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What activates tryptase chymase mast cells?
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opiates, C5a, C3a, vancomycin, IgE, TLRs (2/6 and 4)
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What activates typtase mast cells?
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substance P, IgE, TLRs
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What activates basophils that distinguishes it from mast cells?
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f-met-leu-phe receptor signaling
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What does Imatinib target?
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Kit receptor on mast cells (protoconogene)
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What subunits of the high affinity IgE receptor have ITAMs?
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beta and gamma chain
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What antibody do some chronic idiopathic urticaria patients have?
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IgG antibody to the alpha chain of the high affinity IgE receptor
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What cytokines and chemokines produce after mast cell activation?
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IL-4, 5, 13
TNF alpha Rantes MIP-1 alpha |
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What type of systemic mastocytosis is characterized by B findings and C findings?
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B findings- smoldering mastocytosis
C findings- aggressive mastocytosis |
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What are B findings?
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infiltration of mast cells into organs but no dysfunction.
smoldering mastocytosis |
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What are C findings?
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mast cells are causing dysfunction of target organ
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What cells decrease the high affinity IgE receptor first in patients on Omalizumab?
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basophils
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What is the differential diagnosis of an elevated tryptase?
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end stage renal disease
anaphylaxis leukemias refractory anemia stem cell factor administration |
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What does CD123 do?
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Binds IL-3 on basophils, important for basophil growth
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Mechanism of action of chromones.
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--inihibit IgE mediated calcium channel activation necessary for mast cell degranulation.
--inhibit choride transport which inhibit calcium levels |
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Do chromones block the early or late phase reaction?
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--both
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What bronchoprovocation testing does chromones not protect against?
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Direct Challenges (histamine, methacholine)
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What are uses of chromones?
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Asthma: all ages
any stage of persistent asthma (second line) Eye disease: AC, VKC, GPC Mastocytosis (gastrocrom) |
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When do monocytes committ to becoming a mast cell?
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develop high affinity IgE receptor in the blood and then are committed
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When do mast cells committ to a phenotype (MCtc/c/t)?
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in tissue
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What activates mast cells?
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allergens (via allergen IgE binding FcERI receptor)
IgG (binding FcGRI receptor) Bactria via TLR 2/6 or TLR 4 C3a, C5a Physical stimuli (heat, pressure) Drugs- contrast, opiod, muscle relaxants |
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What is cromolyn sodium inhaler's role in treating asthma?
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Can be steroid sparing but need to use 2-4 puffs TID to QID regularly for 2-4 weeks to see any effect (LABOR INTENSIVE)
**same with nedocromil sodium |
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Why is Cromolyn/Nedocromil's safety profile so good?
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Little to no systemic absorption.
**but unpleasant taste |
