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159 Cards in this Set
- Front
- Back
contain and isolate injury, destroy invading microorg. and inactivate toxins in prep for healing |
What is the purpose of inflammation?
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vascular wall response and inflam cell response
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What are the 2 main components of inflammation?
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early onset, short duration, fluid exudation and PMN emigration
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What are some characteristics of acute inflammation?
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later onset, longer duration, involves lymphocytes and macrophages and induces BV prolif and scarring
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What are some characteristics of chronic inflammation
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heat, redness, edema and pain plus loss of function
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What are the 4 classic signs of inflammation plus the 1 newly added one?
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edema
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excess fluid in interstitial tissue or body cavities
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exudate
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inflammatory extravascular fluid that has high protein concentration and cellular debris
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exudation
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extravasation of fluid, proteins, blood cells from vessels into intersitial tissue or body cavities
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pus
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purulent inflammatory exudate rich in neutrophils and cell debris
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transudate
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extravascular fluid with low protein content
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hydrostatic pressure
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causes fluid to move out of the circulation
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plasma colloid osmotic pressure
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causes fluid to move into capillaries
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decreases
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exudation of protein-rich fluid into intersitial space due to increased vascular permeability ____ osmotic pressure
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stasis
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occurs when fluid loss causes concentration of RBC and increased blood viscosity
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margination
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accumulation of WBC along the endothelium
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formation of venule intercellular endothelial gaps
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most common cause of increased vascular permeability
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chemical mediators
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What causes endothelial cells in venules to contract?
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release of ROS and proteolytic enzymes
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How do leukocytes increase vascular permeability?
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margination/rolling/adhesion, transmigration and migration
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What are the 3 steps in extravasation?
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selectins; sialylated Lewis X
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these bind via lectin domains on cell surface glycoproteins; give an example
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immunoglobulin family: ICAM and VCAM
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these bind integrins on leukocytes
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sialyl-Lewis X
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name the leukocytes receptor that interacts with P-selectin:
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sialyl-Lewis X and PSGL-1
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name the leukocytes receptors that interacts with E-selectin:
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beta integrins: Mac and IFA
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name the leukocytes receptor that interacts with ICAM:
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integrins
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name the leukocytes receptor that interacts with VCAM:
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integrins
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bind to members of the immunoglobulin family and to extracellular matrix:
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modulate the surface expression or avidity of adhesion molecules
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How do chemokines affect adhesion and transmigration?
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P-selectin
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Which receptor is rapidly translocated to the endothelial cell surface after histamine exposure?
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IL1 and TNF
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What mediators activate endothelial cells by inducing E-selectin, ICAM and VCAM expression?
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high-affinity binding form of LFA and Mac (integrins)
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What occur with activation of the leukocyte to allow firm adhesion?
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PECAM on both endothelial cells and leukocytes
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What receptor/molecule is responsible for diapedesis?
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neutrophils
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What leukocytes predominates during the first 6-24 hours of inflam response?
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monocytes
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What leukocytes predominates after 24-48 hours of an inflam response?
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leukocyte surface G-protein-coupled receptor
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To what do chemotactic agents bind to initiate chemotaxis?
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PLAc and kinase activation; increased cytosolic Ca and GTPase activity; polymerization of actin causing cell movement
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What happens when a G-protein-coupled receptor on a leukocyte becomes activated?
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by extending pseudopods that bind the ECM and pull the cell forward
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How do leukocytes move?
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TLRs
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these surface molecules mediate innate leukocyte responses to different classes of microbes
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recognition and binding, engulfment, killing and degradation
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What are the 3 steps of phagocytosis?
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opsonins
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These enhance phagocytosis by binding to the leukocyte receptors:
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Fc fragment and C3b
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What are the major opsonins?
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NADPH oxidase
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O2 dependent mechanisms of phagocytosis occur via activation of this oxidase:
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NADPH oxidase
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This converts O2 to superoxide anion and eventually produces hydrogen peroxide (during phagocytosis):
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myeloperoxidase (MPO)
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this converts hydrogen peroxide and Cl- to hydrochlorite and is the most effective means of killing bacteria
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frustrated phagocytosis (large undigestable material), premature fusion of lysosome, lysosome damage by ingested material (urate)
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lysosomal enzymes can be released into the extracellular space by:
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leukocyte adhesion deficiency type II
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defect in fucose metabolism causing loss of sialyl Lewis X
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leukocyte adhesion deficiency type I
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defective synthesis of beta2 integrins (LFA and Mac)
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Chediak-Higashi syndrome
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defect in phagolysosome formation
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chronic granulomatous disease
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defect in microbicidal activity of leukocyte (NADPH defect)
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histamine and serotonin
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these mediators cause vasodilation and increased cell permeability:
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C3a and C5a (anaphylatoxins)
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these complement fragments cause mast cell release of granules:
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contact with collagen, thrombin, ADP, Ag-Ab complexes and PAF
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these 5 things all cause platelet release of granules:
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complement, kinin and clotting systems
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these 3 plasma-derived mediators play key roles in inflammation:
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activation of C3
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this is the most important step in the complement cascade for its biologic functioning:
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binding of Ab-Ag complex to C1
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this is how the classical pathway of the complement system begins:
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binding of a microbe product (endotoxin) to C1
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this is how the alternative pathway of the complement system begins:
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plasma mannose-binding lectin binds to microbe carb and activates C1
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this is how the lectin pathway of the complement system begins:
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C3a: released; C3b: covalently attached to cell/molecule where complement is being activated
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What is the function of the 2 products of the cleavage of C3?
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C3b and other complement fragments
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These combine to cleave C5
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binds the late components (C5-9) to form the membrane attack complex (MAC)
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What does C5b do after the cleavage of C5?
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C3a and C5a (anaphylatoxins)
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these stimulate histamine release from mast cells and increase vascular permeability and vasodilation
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C5a
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This complement pathway product is a powerful leukocyte chemoattractant:
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C3b
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This complement pathway product is an opsonin:
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DAF (cell associated) and C1 inhibitor (circulating)
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regulates complement activation (2)
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paroxysmal nocturnal hemoglobinuria
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caused by a defect in DAF, characterized by recurrent complement-mediated red cell lysis and anemia
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hereditary angioneurotic edema
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caused by C1 inhibitor deficiency, characterized by episodic potentially life-threatening edema
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kininogens; to form bradykinin
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these plasma proteins are cleaves by kallikreins to form _____
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bradykinin
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causes BV dilation, increased vascular permeability and pain
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12
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Hageman factor
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12 (Hageman factor)
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this clotting factor converts prekallikrein to kallikrein
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12 (Hagemena factor)
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this clotting factor can also activate the fibrinolytic system
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eicosanoids
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these are derived from cell membrane-derived arachidonic acid and are signaling molecules
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cyclooxygenases and lipoxygenases
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2 major enzyme classes of eicosanoids
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prostaglandins and throboxanes
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2 enzymes in the cyclooxygenase class
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cyclooxygenase
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Aspirin inhibits what enzyme?
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leukotrienes and lipoxins
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2 enzymes in the lipoxygenase class
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prostaglandin I2 and E2
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these cyclooxygenases cause vasodilation
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prostaglandin E2
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this cyclooxygenase increases sensitivity to painful stimuli and mediates fever
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thromboxane A2
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this cyclooxygenase causes vasoconstriction
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leukotriene C4, D4 and E4
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these lipoxygenases causes vascular permeability
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leukotriene B4
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this lipoxygenase is a chemotactic agent
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lipoxins
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these lipoxygenases may be engogenous negative regulators of leukotriene action
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PAF
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phospholipid derived mediator produced by mast cells and other leukocytes
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PAF
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causes platelet aggregation, vasodilation, increased vascular permeability and increased leukocyte adhesion and chemotaxis
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cytokines
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these are produced mostly by activated lymphocytes and macrophages
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IL and TNF
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these are the major cytokines mediating inflammation
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activated macrophages
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TNF and IL are produced mainly by what cell?
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activate endothelial cells; induce acute-phase response; regulate body mass (TNF) by suppressing appetite
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these are the functions of TNF and IL:
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cachexia; TNF
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pathologic state characterized by weight loss and anorexia accompanying some infections and neoplasias; is caused by sustained production of ______
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CXC
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class of chemokine that acts to recruit neutrophils
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CC
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class of chemokine that recruit monocytes, eosinophils, basophils and lymphocytes
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C
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class of chemokine that are relatively specific for lymphocytes
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CX3C
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class of chemokine that promotes firm adhesion of lymphocytes and monocytes (cell surface form) and is a chemoattractant (soluble form)
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through G-protein-linked receptors
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How do chemokines mediate their activites?
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endothelium-derived relaxation factor
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What is an alternate name for NO?
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inhibits platelet aggregation and adhesion; kills certain microbes and tumor cells
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Actions other than vasodilation of NO include:
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eNOS
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Which type of NOS is responsible for maintaining vascular tone?
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iNOS
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What type of NOS is responsible for reducing leukocyte recruitment?
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specific (secondary) and azurophil (primary)
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What are the 2 granules types of the neutrophil?
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specific (secondary)
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What type of neutrophil granule contains lysozyme, collagenase, gelatinase, lactoferrin, plasminogen activator and histaminase
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azurophil (primary
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What type of neutrophil granule containsmyeloperoxidase, lysozyme, defensins, acid hydrolase, neutral protease
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Substance P
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neuropeptide that is a mediator of vascular permeability, transmits pain signals, regulates BP and stimulates immune and endocrine cell secretion
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prostaglandins, NO, histamine
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these mediators are important to vasodilation:
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vasoactive amines, C3a and C5a (liberate amines), bradykinin, leukotrienes, PAF, substance P
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these mediators are important to increased vascular permeability:
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C5a, leukotriene, chemokines, IL, TNF, bacterial products
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these mediators are important to chemotaxis:
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IL, TNF, prostaglandins
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these mediators are important to fever
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prostaglandins, bradykinin
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these mediators are important to pain:
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neutrophil and macrophage, lysosomal enyzmes, oxygen metabolites, NO
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these mediators are important to tissue damage:
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resolution, fibrosis, progression to chronic inflammation
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3 outcomes of acute inflammation:
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serous inflammation
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type of acute inflammation involving tissue fluid accumulation, indicates modest increase in vascular permeability
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fibrous inflammation
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type of acute inflammation involving marked increases in vascular permeability, exudates with fibrinogen
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suppurative or purulent inflammation
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type of acute inflammation involving production of purulent exudates consisting of leukocytes and necrotic cells
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infiltration with macrocytes, lymphocytes and plasma cells, tissue destruction, angiogenesis and fibrosis
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these are characteristics of chronic inflammation:
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cytokines produced by T cells (interferon gamma) and nonimmune factors (endotoxins)
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these 2 types of mediators activate macrophages:
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interferon gamma
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This is the most important activating factor for macrophages
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eosinophils
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this cell type is characteristic of immune reactions mediated by IgE and parasitic infections
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eotaxin (a CC chemokine)
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eosinophil recruitment is dependent on this chemokine:
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major basic protein (MBP)
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eosinophil granules contain this:
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granulomatous inflammation
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this distinctive form of chronic inflammation is characterized by focal accumulation of activated macrophages
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enlarged and flattened; epitheliod macrophages
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this is what macrophages look like and are called upon activation:
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TB
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a granuloma that is called a tubercle is caused by this:
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lymphoid follicle and sinusoidal phagocyte hyperplasia
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nodal enlargement during lymphadenitis is caused by:
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acute phase responses; severe cases are systemic inflammatory response syndrome (SIRS)
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systemic changes associated with inflammation are collectively known as:
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fever, production of acute phase proteins, leukocytosis, increased BP and HR, decreased sweating, anorexia
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what are some clinical and pathological acute phase responses?
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pyrogens
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substance that stimulate prostaglandin synthesis in the hypothalamus
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C-reactive protein, fibrinogen and serum amyloid A protein
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3 of the best known acute phase proteins are:
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leukemoid reactions
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extraordinary high levels of leukocytes
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neutrophilia
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bacterial infections usually cause this type of leukocytosis
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lymphocytosis
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viral infections usually cause this type of leukocytosis
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eosinophilia
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parasitic infections usually cause this type of leukocytosis
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DIC, hypoglycemia and septic shock
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sepsis induced release of large amounts of cytokines can cause this clinical triad:
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Vasodilation, edema, and tissue damage respectively
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To what tissue processes do the cardinal signs of inflammation, redness, heat and swelling correspond?
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Blood flow and plasma volume
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In considering the forces that regulate fluid distribution, what are the two determinants of hydrostatic pressure?
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By exposure to negatively charged surfaces
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How is the the Hageman factor (clotting factor 12) activated?
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By stimulating tissue and inflammatory cells to secrete additional inflammatory mediators
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How do kinins amplify the inflammatory response?
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Cell lysis by the membrane attack complex
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What is the end point of compliment binding to cells?
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One moleclule of C1q , two molecules of C1r and two molecules of C1s
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What are the components of the C 1 complex?
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By the action of activatated of C1 on C4
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How is C3 convertase produced?
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C6, C7, and C8 bind the cell membrane in sequence and C7 forms a channel through the lipid bilayer
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How does the membrane attack complex (MAC) lyse cells?
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Factor 1 and serum carboxypeptidase
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What two plasma enzymes inactivate complement?
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Some viruses and mycobacteria use cell bound complement components to facilitate their entry into cells
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How might complement be exploited by infectious agents?
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Membrane Phospholipids
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From what cell components are arachidonic acid and platelet activating factor derived?
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By inhibiting cyclooxygenases 1 and 2 (COX-1 and COX-2)
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How do non-steroidal anti-inflammatory drugs exert the effects on prostaglandin synthesis?
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A mixture of leukotrienes
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What is slow reacting substance of anaphylaxis?
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Heat Shock Proteins
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What stress induced protein family helps protect from inflammatory injury?
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Nervous, immune, and endocrine systems
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What systems are linked by neurokinins?
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By injury to nerve terminals during inflammation
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How are neurokinins released?
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They are potent vasoconstrictors and vasopressors
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What are the effects of endothelins?
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Dendritic cells
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Which cell type is the most effective antigen presenting population?
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Immunoglobulin E
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Which immunoglobulin type is found on the surface of mast cells and basophils?
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Contact with filbrillar collagen of with thrombin
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What are the main stimuli for platelet aggregation?
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Azurophillic granules
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Which neutrophil granules are most important in killing bacterial invaders?
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Serine proteinases and Metalloproteinases are neutral and act in the extracellular fluid. Cysteine and aspartic proteinases are acidic and act in the acidic environment of phagocytic lysosomes
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Where do the four types of neutrophil proteinases act?
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They reduce production of a powerful pro-inflammatory cytokine tumor necrosis factor alpha (TNF-a)
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How do anti-inflammatory cytokines like IL 6 limit inflammation?
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Infectious agents, trauma, cancer, and immune reactions
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What are the four major causes of chronic inflammation?
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Matrix Metalloproteinases and cysteine proteases
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The activities of what enzymes are central to the tissue destruction of chronic inflammation?
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By granuloma formation
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How does the body protect itself from chronic infection from organisms that cannot be destroyed by neutrophils?
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Langhans giant cells |
What are the characteristic cells in multinucleated granulomas formed in response to foreign infectious agents such as tuberculosis?
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IL 13 and transforming growth factor beta
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Which cytokines are most important in the progression of granulomas to fibrotic nodules?
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Pain
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What is the result of the stimulation of nociceptors?
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