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85 Cards in this Set
- Front
- Back
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what do myeloid stem cells give rise to?
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cells of the innate immne system
- neutrophils - eosinophils - basophils - mast cells - macrophages |
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what do lymphoid stem cells give rise to?
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cells of the adaptive immune system
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what are the three granulocytes?
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neutrophils
eosinophils basophils |
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what do basophils and mast cells bind to?
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IgE
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what do TH1 cells produce, and what do they affect?
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IFN-g, IL-2
influence cell mediated response of CD-8 and CD 4 cells |
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what do TH2 cells produce, and what do they affect?
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IL-4, IL-5, IL-10
enhance antibody production by B cells |
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which T cell subtype is more associated with autoimmunity?
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Th2
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where is histamine synthesized and stored?
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in granules of mast cells and basophils
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why is histamine called the vasoactive amine?
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dilation of arterioles and postcapillary venules
constriction of veins contraction of endothelial cells |
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what type of proteases make up the complement system?
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serine proteases
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what are the two ways in which complement can be activated?
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1. antigen-antibody interaction (classical)
2. interaction with foreign surfaces (alternative pathway) 3. interaction with mannose binding lectin (lectin pathway) |
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what does C3b do?
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opsonizes
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what do C3a and C5a do?
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mediate leukocyte chemotaxis
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what are eicosanoids?
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metabolites of arachadonic acid
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name two cytokines from the hematopoietic lineage that are not IL-1 and TNF-a
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GM-CSF (granulocyte-monocyte colony stimulating factor)
G-CSF (granulocyte colony stimulating factor) |
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what is a leukocyte
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a white blood cell
- monocyte - lymphocyte - granulocyte |
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name two inflammatory mediators that are important for chemotaxis
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C3a
leukotriene B4 (LTB4) |
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celecoxib
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COX-2 selective inhibitor
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etanercept
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TNF-a antagonist
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prednisone
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glucocorticoid
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what is arachadonic acid synthesized from?
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linoleic acid, which is derived only from dietary sources
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how does arachidonic acid exist in the membrane?
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esterified to the membrane phopholipids:
phosphatidylcholine phosphatidylethanolamine |
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how is arachadonic acid released from the cellular membrane?
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phospholipase A2
rate determining step |
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what induces phospholiase A2 release?
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TNF-a, CM-CSF, INF-g, EFG, MAPK-PKC cascade
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what inhibits phospholipase A2 release?
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glucocorticoids
induces synthesis of lipocortin- a family of phospholipase A2 inhibiting proteins |
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what are three proteins that act onunesterified arachidonic acid?
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1. cyclooxygenase
2. lipoxygenase 3. epoxygenase |
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lipoxygenase pathway
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lipoxins
leukotrienes |
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cyclooxygenase pathway
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prostaglandins
prostacyclin thromboxane |
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cytochrome P450 epoxygenases
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epoxyicosatetraenoic acids (EETS)
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what is the common chemical structure shared by prostaglandins?
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prostanoid: 20 carbion carboxylic acid
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synthesis pathway of prostaglandins
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PGG2 --> PGH2 --> PGD2,PGE2, PGF2, thromboxane A2, porstacyclin (PGI2)
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why is PGE2 important?
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cytoprotective roles for gastric mucosa, myocardium, and renal parenchyma
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what is the chief eicosanoid product of platelets?
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thromboxane A2 (TXA2)
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what does TXA2 do?
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vasoonstriction
promoter of platelet adhesion and aggregation |
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what is the chief eicosanoid product of the vascular endothelium?
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PGI2 (prostaglandin I2)
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what does PGI2 do?
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asodilator, venodilator, and inhibiotr of platelet aggregation
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what is the balance that mediates systemic blood pressure and thrombogenesis?
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TxA2 (vasoconstrictor and platelet activator) vs. PGI2 (vasodilator and platelet inhibitor)
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LTB4
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proinflammatory sequelae:
neutorphil chemotaxis aggregation transmigration through epithelium and endothelium upregulates free radical production for killing |
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what do lipoxins LXA4 and LXB4 do?
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modulate the effects of leukotrienes (possibly negative regulators, and a key player in the resolution of inflammation)
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what are EETs?
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epoxyeicosatetraenoic acid: derivatives from oxidized arachidonic acid (via cytochorme P450 epoxygenases)
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what do EETs do?
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also a negative regulator of inflammation
inhibit platelet COX and inhibot expression of ICAMs |
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what does the cytokine cascade in asthma cause?
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generation of PGD2 and leukotrienes (LTB2)
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give 2 extremely potent bornchoconstrictive compounds
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LTC4 and LTD4: 1000x more potent than histamine in asthma
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what is found in both UC and IBD?
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elevated LTB4 levels --> abnormal leukocyte infiltration into the parenchyma
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what type of cancer risk is exacerbated in UC and IBD?
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adenocarcinoma of the colon
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what is found to be elevated in the synovial fluid of patients with RA?
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COX-2 enyzme and PGE2
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what will autoimmune distruction show in blood tests?
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high erythrocyte sedimentation rate and low hematocrit
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give the mechanism of glomerulonephritis
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elevated levels of LTB4 leads to the synthesis of LTC4 and LTD4 --> facilitate neutrophil adhesion to clomerular mesangium and epithelium
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what role does LTC4 and LTD4 play in glomerulonephritis?
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decrease renal blood flow and GFR
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what type of cancer has COX2 inhibitors been approved for?
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familial adenomatous polyposis
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how do glucocorticoids work?
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induce a family of lipocortins, which inhibit the actin of Phospholipase A2 and thereby inhibits the release of arachadonic acid.
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what are the three functions of NSAIDs?
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1. anti-inflammatory
2. antipyretic 3. analgesic |
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what is the mechanism of NSAIDs?
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reversible, competitive inhibitor of COX1 and/or COX-2
(aspirin is non-reversible) |
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what is a caveat associated with NSAIDs?
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only suppress the signs of the underlying inflammatory disease
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what can COX-1 inhibitors precipitate?
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NSAID-induced gastropathy, since you've gotten rid of the protective effects of COX-1 eicosanoid products
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naproxen
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NSAID with long elimiation half life
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salicylate
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NSAID with long elimiation half life
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piroxicam
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NSAID with long elimiation half life
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phenylbutazone
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NSAID with long elimiation half life
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aspirin
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a salicylate
irreversible inhibitor of COX1/2 by acetylating the active site serine residue |
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how does aspirin act as a antithrombogenic agent?
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provents platelets from synthesizing TxA2
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what is the difference between aspirin's action on platelets and on endothelial cells?
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platelets are anuclear- cannot synthesize new TxA2
endothelial cells cna synthesize new COX1 protein and resume synthesis of PGI2 |
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what does aspirin do to COX-2
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only partially inactivates it. you get aspirin-triggere lipoxins (ATLs) that function lipoxins as anti-inflammatory agents
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what are the two side effects to aspirin?
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1. aspirin-induced airway hyperreactivity in asthmatics
2. Reye's syndrome` |
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what is Reye's syndrome?
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hepatic encephalopahty and liver steatosis in young children
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abatacept
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T cell costimulation modulator
treates RA |
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almotriptan
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treats migrane headaches
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alfuzosin
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a-adrenergic blocker for BPH
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aprepitant
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substance P antagonist
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balsalazide
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anti-inflammatory for IBD
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betaseron
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INF-b used to treat MS
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bivaldirudin
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anticoagulant
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bosentan
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endothelin receptor antagonist.
used for pulmonary artery hypertension |
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brinzolamide
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Carbonic anhydrase inhibitor
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candesartan
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angiotensin II receptor antagonist for treatment of HTN
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caspofungin
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antifungal against aspergillus and candida
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cefdinir
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broad spectrum antibiotic used for treatment of bacterial infections of ear, sinus, throat and skin
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cilostazol
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treatment for intermittent claudication
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darbpoetin
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stimulates erythropoiesis for anemia treatment
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darunavir
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protease inhibitor for HIV treatment
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Daytrana
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used to treat ADD (ritalin)
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dofetilide
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class III antiarrythmic
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dotrecogin alfa
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recombinant form of Protein C
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dutasteride
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5-alpha reductase inhibotor
used to treat BPH and male pattern baldness |
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efalizumab
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used to treat psoriasis
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