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101 Cards in this Set
- Front
- Back
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What two substances first cause vasodilation and where do they act first?
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1. NO and Histamine
2. Arterioles |
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What are the six ways endothelium becomes leaky?
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1. Gaps in Venules
2. Vascular Injury 3. Leukocyte mediated injury 4. Transcytosis 5. New Vessel Formation 6. Delayed prolonged leakage |
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What is the immediate transient response and what four things contribute to it?
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1. Leakage due to gaps in venules
2. Bardykinin, Histamine, Nueropeptide P and leuokotrines |
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What causes gaps in venules in about 4-6h after injury(3).
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1. IL-1
2. TNF 3. INF-Gamma |
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What is the immediate sustained response?
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Leakage after vessel injury
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Endothelial cell detachment is often associated with what(2)?
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1. Platelet aggregation
2. Thrombis |
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What causes the injuries in leukocyte mediated injury(2)?
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1. ROI
2. Lysosomal enzymes |
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Leukocyte mediated injury is restricted to what areas?
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Vascular sites (pulmonary and glomerular capillaries)
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What is the organelle in transcytosis? What factor does it respond to?
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1. Vesiculovacuolar organelle
2. VEGF and maybe histamine |
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New vessels have a high concentration of what?
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Vascular mediator receptors
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What causes the margination of leukocytes?
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Stasis
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What is called when a vessel wall starts to become covered in leukocytes?
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Pavementing
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What are the four classes of adhesion receptors?
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1. Selectins
2. Immunoglobin family 3. Integrins 4. Mucin-like glycoproteins |
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What are the two Beta-2 integrins? The one Beta-1?
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1. LFA-1 and Mac-1
2. VLA-4 |
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Mucin-like glycoproteins bind to what leukocyte adhesion molecule?
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CD44
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What causes P-Selectins to migrate to the surface of the endothelium(3)?
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1. PAF
2. Histamine 3. Thrombin |
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In regards to the activation of adhesion molecules for the initiation of inflammation, what causes CAMs to be expressed on post-capillary venules(2)?
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1. IL-1
2. TNF |
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What causes the expression of VCAM and ICAM on the surface of the endothelium(2)?
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1. IL-1
2. TNF |
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What causes the integrins VLA-4 and LFA-1 to change to a high affinity state?
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Chemokines binding to heparan sulfate GAGs.
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WHat is one homophilic molecule that helps in the process of diapedesis?
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PECAM or CD31
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Where does diapedesis mainly occur?
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The venules
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What surface molecule is used in the retention of leukocytes?
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CD44
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What enzyme is lacking in people with LAD-2?
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Fucosyl Transferase
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What are three examples of endogenous chemokines?
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1. Complement - 5a
2. LTB4 3. IL-8 |
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All chemokines activate what type of recptors?
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GPCR
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Name four Ca+ regulating proteins.
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1. Calmodulin
2. Gelosin 3. Filamin 4. Profilin |
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Elevated Ca+ levels activate what two enzymes?
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1. Phospholipase A2
2. Protein kinase C |
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When activated, leukocytes do what four things?
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1. Release metabolites of AA via phospholipase A2
2. Release lysosomal enzymes such and activate respiratory burst 3. Release cytokines 4. Change their CAMs |
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What two types of leukocyte receptors are involved in leukocyte activation?
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1. Toll-like Receptors
2. GPCR |
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TLRs are activated in response to what?
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Microbes and their products
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What is the most important cytokine receptor expressed by leukocytes? What produces it?
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1. INF-Gamma
2. NK cells and Activated T Cells |
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What is the most effiecent antibody for opsonization?
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IgG
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What complement product acts in opsonization?
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C3b
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What does C1q bind to for opsonization?
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Mannose binding lectin (MBL)
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What are the three steps in phagocytosis?
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1. Recognition and attachment
2. Engulfment 3. Killing and degradation |
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Recognition for phagocytosis is accomplished by what two types of receptors?
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1. Mannose Receptor
2. Scavenger Receptor |
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Engulfment in phagocytosis is dependent on what?
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Actin polymerization
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What enzyme produces ROIs for killing in phagocytosis?
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NADPH Oxidase
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What emzyme is the most efficient killer of microbes in neutrophils?
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Myeloperoxidase
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Name five oxygen independent killing mechanisms.
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1. Bacterial Permeability Increasing protein (BPI)
2. Major Basic Protein - parasites 3. Lactoferrin 4. Defensins 5. Lysozyme |
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Name four scenarios where leukocyte lysosomal products are released into the extracellular space.
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1. The phagolysosome is transinently open
2. The phagolysosome tries to eat something immobile or too big 3. The phagolysosome eats something that has membranolytic properties 4. Exocytosis |
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How is Chediak-Higashi Syndrome inherited? What is wrong in the disease? What is the major morphological feature?
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1. Autosomal recessive
2. Cannot get lysosomal enzymes into the lysosome 3. Giant granules in the cell |
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How is Chronic Granulomatous Disease inherited. What is the major inheritence? What is the problem in this disorder?
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1. X-Linked(gp91phox) and Autosomal Recessive (p47phox and p67phox)
2. X-Linked 3. NADPH Oxidase failure |
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What are the two sources of chemical mediators of inflammation? What is different about the mediators in each?
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1. Plasma
2. Cellular products 3. Plasma mediators have to be activated |
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What are the two causes of the termination of the actue inflammatory response?
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1. Reduction in the number of mediators in circulation
2. Release of anti-inflammatory mediators |
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What are three examples of anti-inflammatory mediators?
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1. TGF-Beta
2. Lipoxins 3. Neurologic inhibition (cholinergic) |
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Histamine is a major player in what? What is the major source of histamine? What are three effects of histamine? What type of receptors does histamine bind to?
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1. Immediate transient response
2. Mast cells 3. Vasodilation, Increased vascular permeability and vasoconstriction in large arteries 4. H1 receptors |
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What is the major source of seratonin?
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1. Platelets and enterochromaffin cells
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What substance is released from mast cells that causes platelets to aggregate?
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PAF
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The complement system bridges what two immune functions?
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1. Innate Immunity
2. Adaptive Immunity |
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What are the three main effects of the complement system?
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1. Increased membrane permeability
2. Opsonization 3. Chemotaxis |
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What is the most important step in the complement activation?
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Activation of C3
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C3a, C4a and C5a have what function?
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Anaphylatoxins - cause the release of histamine from mast cells
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C5a does what four things?
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1. Activates lipoxygenase system
2. Activates leukocytes 3. Chemotaxis 4. Enhances adhesion |
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Opsonization is accomplished by what product of the complement system?
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C3b and iC3b
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What factor converts prekallirein to kallikrein? What does kallikrein do next?
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1. Hageman factor
2. Converts HMWK to bradykinin |
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What are four functions of bradykinin? What two molecules degrade bradykinin?
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1. Pain
2. Vasodilation 3. Increased vascular permeability 4. Contraction of smooth muscle 5. Kininase and ACE |
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What produces the main link between inflammation and clotting?
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Thrombin (Factor IIa)
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What factor starts the clotting cascade?
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Hageman (12a)
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What action does thrombin take in the clotting cascade? What type of receptor does thrombin bind to and what is the result?
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1. Cleaving fibrinogen to form fibrin
2. Protease Activated Receptor (PAR - GPCR) 3. P-Selectin, Chemokines, COX, NO and PAF, Endo cell shape change and CAM changes |
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What are three functions of plasmin?
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1. Lyse fibrin clots (also produces fibrin split products which increase vascular permeability)
2. Activate complement C3 (inflammatory) 3. Activate Hageman (Factor XII) |
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Factor XII can activate what four systems?
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1. Clotting
2. Fibinrolytic 3. Kinin 4. Complement |
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What is an autocoid?
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Short range hormone
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Is AA free in cells? What enzyme releases it?
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1. No it is esterfied to cell membranes.
2. Phosphalipase A2 |
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What is the class of metabolites from AA breakdown called?
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Eicosanoids
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Which COX enzyme is constitutive?
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COX-1
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What product of COX is a pro-coagulant?
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TxA2
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What product of COX works against TxA2?
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PGI2
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What product of COX is hyperalgesic?
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PGE2
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What is the major metabolite of the COX pathway in mast cells? What does it do?
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1. PGD2
2. Vasodilation and increased vascular permeability |
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What is the predominant enzyme in the lipoxygenase pathway? What is its main product?
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1. 5-LO
2. 5-HETE |
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What are the two functions of LTB4?
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1. Chemotaxsis
2. Activator of neutrophils |
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What are the three functions of LTC4, LTD4 and LTE4?
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1. Vasoconstriction
2. Increased permeability 3. Bronchospasms |
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What type of receptors do leukotrines bind to?
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Cysteinyl receptors
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What produces lipoxins and what do they do? What also blocks leukocye recruitment?
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1. Platelets (12-LO)
2. Stop inflammatory responses 3. Resolvins |
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Glucocorticoids upregulate what substance which prevents AA from being freed from cell membranes?
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Lipocortin-1
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What does PAF cause?
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Activation of everything associated with inflammation
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What type of cells mainly produce IL-1 and TNF?
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Macrophages
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What are the major cytokines of inflammation(2)? What do they do to endothelium?
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1. IL-1
2. TNF 3. "Activate" it meaning up-regulate gene expression of inflammatory genes |
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What does TNF do to neutrophils?
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Prime them for attack
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What is system actuse phase response(6)? What causes it?
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1. Fever
2. Loss of appetite 3. Slow wave sleep 4. Release of neutrophils 5. Release of corticosteroids and tropins 6. Septic shock |
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What cytokine can contribute to cachexia?
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TNF
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What are the sour examples of chemokines and the examples of each?
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1. C-X-C: IL-8
2. C-C: MIP, MCP, Eotaxin, RANTES 3. C - specific for lymphocytes 4. C - X3 - C: Fractalkine - monocytes and T Cells |
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What kind of action does NO have? What induces the production from iNOS?
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1. Paracrine action that induces cGMP production that in turn causes vasodilation
2. Cytokines |
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Overall, what is NO? What are three functions of NO?
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1. Reducer of inflammation
2. Inhibits platelt aggregation 3. Inhibits mast cell induced inflammation 4. Regulates leukocyte recruitment |
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How is NO bacteriacidal?
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Combines with ROIs to make RNIs.
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What are the two types of neutrophil granules? What is different about the releasal of each?
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1. Primary/Azurophilic and Secondary/Specific
2. Azurophilic granules need high amounts of mediators present to cause their releasal |
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What cleaves elastase?
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Alpha-1 Antitrypsin
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High levels of ROI can do what three things?
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1. Damage endothelium (xanthine oxidation)
2. Damage antiproteases 3. Damage tissue |
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Name five antioxidants.
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1. Ceruloplasmin
2. Transferrin 3. GPoxidase 4. SOD 5. Catalase |
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What are the four functions of neuropeptide P?
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1. Regulate BP
2. Pain 3. Endocrine secretion 4. Increase vascular permeability |
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Hypoxia induced factor increases the release of what?
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VEGF
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Name three early vasodilators.
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1. Histamine
2. NO 3. Prostaglandins |
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Increased vascular permeability caused by what six things?
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1. Histamine
2. Kinins 3. Anaphylatoxins 4. LTE LTD LTC 5. PAF 6. Substance P |
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Chemotaxis is cause by what three things?
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1. C5a
2. LTB4 3. Chemokines - IL-8 |
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Prostaglandins cause what four things?
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1. Pain
2. Vasodilation 3. Fever 4. Edema |
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TNF and IL-1 cause what three things?
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1. Endo Leuko interactions
2. Active phase reactants 3. Leukocyte recruitment |
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What three situations lead to chronic inflammation?
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1. Persistent infections
2. Prolonged exposure to toxic agents 3. Auto-immunity |
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What are the three morphologic features of chronic inflammations?
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1. Mononuclear infiltration
2. Tissue distruction 3. Fibrosis |
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What are two endogenous pyrogens?
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1. TNF
2. IL-1 |
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What replaces apolipoprotein and causes HDLs to be the main NRG source for macrophages?
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Serum Amaloid A
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