Term
| what leads to production of inflammatory mediators? (4) |
|
Definition
| trauma, foreign body, infectious agents, necrosis (toxic, ischemic) |
|
|
Term
| 2 inflammatory mediator groups |
|
Definition
| chemical mediators and chemotactic factors |
|
|
Term
|
Definition
| changes in blood flow > heat, redness. pain. increased permeability > swelling |
|
|
Term
| chemotactic factors > > (2) |
|
Definition
| recruitment and stimulation of inflammatory cells > acute inflammation and chronic inflammation |
|
|
Term
| acute inflammation cells (3) |
|
Definition
| neutrophils, mast cells, platelets |
|
|
Term
| chronic inflammation cells (3) |
|
Definition
| macrophages, lymphocytes, plasma cells |
|
|
Term
| inflammation is a _ host response |
|
Definition
|
|
Term
| 2 major components of inflammation |
|
Definition
| vascular reaction and mobilization of cells |
|
|
Term
| vascular reaction and mobilization of cells are mediated by _ derived from _ (2) |
|
Definition
| chemical messengers, plasma proteins or host cells |
|
|
Term
| t/f usually the outcome of acute inflammation is successful in killing and eliminating the invading microorganism |
|
Definition
| true. it usually resolves and the tissue returns to normal or is repaired. |
|
|
Term
| inflammation is one component of |
|
Definition
| the innate immune response |
|
|
Term
|
Definition
| fibroblasts, connective tissue matrix - structural and adhesive proteins |
|
|
Term
| connective tissue matrix made from |
|
Definition
| elastic fibers, collagen fibers and proteoglycans |
|
|
Term
| another name for a neutrophil |
|
Definition
| polymorphonuclear leukocyte |
|
|
Term
| the most important chemical mediators of inflammation are derived from (2) |
|
Definition
| either a cellular source or from the plasma |
|
|
Term
| 2 types of chemical mediators derived from a cellular source |
|
Definition
| preformed mediators in secretory granules, newly synthesized mediators |
|
|
Term
| preformed mediators of inflammation in secretory granules (derived from a cellular source) (3) |
|
Definition
| histamine, serotonin, lysosomal enzymes |
|
|
Term
| newly synthesized chemical mediators of inflammation from a cellular source (6) |
|
Definition
| prostaglandins, leukotrienes, platelet-activating factors, activated oxygen species, nitric oxide, cytokines |
|
|
Term
|
Definition
| mast cells, basophils, platelets |
|
|
Term
|
Definition
|
|
Term
| source of lysosomal enzymes |
|
Definition
|
|
Term
|
Definition
| all leukocytes, platelets, EC |
|
|
Term
|
Definition
|
|
Term
| source of platelet-activating factors |
|
Definition
|
|
Term
| source of activated oxygen species |
|
Definition
|
|
Term
|
Definition
|
|
Term
|
Definition
| lymphocytes, macrophages, EC |
|
|
Term
| major source of chemical mediators to the plasma |
|
Definition
|
|
Term
| two types of plasma chemical mediators of inflammation |
|
Definition
| complement activation, factor XII (Hageman factor) activation |
|
|
Term
| (2) factor xii (hageman factor) activation |
|
Definition
| kinin system, coagulation/fibrinolysis system |
|
|
Term
| (4) complement activation |
|
Definition
| anaphylatoxins (bind neutrophils and macrophages): C3a, C5a. C3b (phagocytosis/opsonization), C5b-9 (MAC) |
|
|
Term
| the chemical mediators that are derived from plasma circulate as / act by |
|
Definition
| inactive precursors, activated by a cascad of proteases, and act by bindingto specific receptors on target cells |
|
|
Term
| plasma mediators are fast/slow |
|
Definition
| fast - don'tneed to be produced, just activted. have short lifespan |
|
|
Term
|
Definition
| Factor XIIa > kinin cascade (bradykinin, kallikrin>plasmin>complement cascade) and clotting cascade (thrombin>fibrin) |
|
|
Term
|
Definition
| causes increased vascular permeability and pain. created from HMWK in the kinin cascade of the kinin system |
|
|
Term
|
Definition
| RBCs and platelets in a mesh of fibrin |
|
|
Term
| functions of plasmin in inflammation |
|
Definition
| cleaves and activates C3. results in clot lysis and release of fibrin-split products. |
|
|
Term
|
Definition
| result in increased vascular permeability. are made because of plasmin. |
|
|
Term
| general principles of clotting cascade and fibrinolysis |
|
Definition
| amplification of response by positive feedback loops. release of secondary mediators that may dampen the response. |
|
|
Term
| 3 pthways that activate the complement system |
|
Definition
| classical pathwy - IgG or IgM + C1. alternative pathway - direct activation of cell wall components of bacteria, fungi or toxins (cobra venom), lectin pathway - mannose binding lectin attaches to mannose on bacterial cell wall +C1 |
|
|
Term
| bacteria that have evolved blocks to stop MAC (4) |
|
Definition
| salmonella, meningococcus, gonococcus, streptococcus (has C3b peptidase instead of physical block) |
|
|
Term
| resistance to phagocytosis example |
|
Definition
| pneumococcus - polysaccharide capsule |
|
|
Term
| resistance to complement activation examples (2) |
|
Definition
| menngitis- sialic acid inhibits C3 and C5 convertases. streptococcus - M protein blcks C3 and C3b binding |
|
|
Term
| release of histamine is triggered by |
|
Definition
| trauma, cold, igE receptors, C3a C5a, histamine-releasing actors, cytoknes IL1 IL8 and chemokines |
|
|
Term
|
Definition
| vasodilation, increase vascular pereability,bnd to H1 reeptors in vessel wall. acts locally, quickly degradded. |
|
|
Term
| release o serotonin triggered by / function |
|
Definition
| thrombn, exposed subendothelial collagen, PAF Platelet Activating Factor / increases vascular permeabiliy like histamine and fibrin splits |
|
|
Term
| arachidonic acid metabolites (2) |
|
Definition
| prostaglandins, leukotrienes |
|
|
Term
|
Definition
| rapidly synthesized by mast cells, neutrophils, platelets, macrophages, endothelial cells. increases vascular permeability like serotonin, histamine and fibrin splits. also activates platelets and leukocyte adhesion, chemotaxis, and activation |
|
|
Term
| arachidonic acid cascade / major categories of these drugs |
|
Definition
| major target for drugs that alleviate pain and suppress inflammation. 1. corticosteroids 2. aspirin and NSAIDs 3. selective COX2 inhibitors |
|
|
Term
| what do corticosteroids do |
|
Definition
|
|
Term
| what do aspirin and non-steroidal anti-inflammatory drugs do |
|
Definition
| inhbit COX1 (constitutive) and COX2 (inducible) > inhibit prostaglandins specifically |
|
|
Term
| selective cox2 inhibitors |
|
Definition
| fewer gastric side effects, possible prothrombotic effect > inhibit prostaglandins specifically |
|
|
Term
|
Definition
|
|
Term
|
Definition
| PGI2 nd TXA2, lead to PGD2 and PGE2, vasodilation and increased vascular permeability |
|
|
Term
|
Definition
| anti inflammatory (inhibit neutrophil adhesion and chemotaxis). come from arachidonic acid but not the COX pathway ( came from lipoxygenase pathway) |
|
|
Term
|
Definition
| enzyme activity issupressed by steroids. isthe rate limiting enzyme for arachidonic acid synthesis |
|
|
Term
|
Definition
| ajor target for anti inflammatory drugs |
|
|
Term
| the next gneration of anti inflammatory drugs |
|
Definition
|
|
Term
| there is cell and tissue _ in expression of enzymes in synthesis of prostaglandins and leukotrienes |
|
Definition
|
|
Term
|
Definition
| PL A2 has a calcium channel that pulls PLs off cell membranes |
|
|
Term
| 5 functions of arachidonic acid metabolites |
|
Definition
| vasoconstriction (TXA2, LTC4, LTD4, LTE4), vasodilation (PGI2, PGD2, PGE2) [die], incrased vascular permeability (LTC4, LTD4, LTE4), chemotaxis (LTB4, HETE), inhibition of chemotaxis (lipoxins) |
|
|
Term
| arachidonic acid metabolites fast/slow, act where |
|
Definition
| are rapidly synthesized, act locally at the site of synthesis, and are rapidly broken down |
|
|
Term
| prostaglandins and leukotrienes bind to |
|
Definition
| G-protein coupled receptors expressed on the surface of inflammatory cells. activation of these receptors is responsible for most of the key steps involved in acute inflammation. |
|
|
Term
| cytokines (2) / pathway (4) |
|
Definition
| IL-1, TNF-alpha. in the class of newly synthesized cell-derived mediators. / bacterial products, Ag-Ab complexes, toxins, physical injury > macrophage activation > IL1 and TNFa catalyze 1. leukocytes > cytokine secretion, 2. endothelial cells > cytokine secretion and leukocyte adhesion, 3. fibroblasts > wound healing, 4. systemic effects (fever, sleep) |
|
|
Term
|
Definition
| are critical cells in acute inflammation. they mediate the transition between innate and adaptive immunity and also initiate tissue repair and wound healing. |
|
|
Term
| molecules produced in active macrophages |
|
Definition
| phagocyte oxidase> ROS, iNOS> NO, cytokines (TNF, IL12), INF-gamma > fibroblast growth factors+ angiogenic factors+ metalloproteinases, increased MHC molecules and costimulators |
|
|
Term
| effector functions of activated macrophages |
|
Definition
| ROS+NO= killing of microbes, cytokines= inflammation and enhanced adaptive immunity, fibroblast gf+angiogenic factors+ metalloproteinases=tissue remodeling, increased MHC molecules and costimulators= enhanced antigen presentation. |
|
|
Term
|
Definition
| different ones are activated by different microbes. PAMPs bind to them. |
|
|
Term
|
Definition
| damage associated molecular patterns: necrosis produces them > acute inflammation |
|
|
Term
| gram positive bacteria / example |
|
Definition
| stains purple on gram staining because peptidoglycan in the cell wall is on the outside and thus accessible to stain. / staphylococcus |
|
|
Term
| gram negative bacteria / what is released |
|
Definition
| stain pink / lipopolysaccharides (LPS) are released from gram negative bacteria when they replicate and invade into tissues. |
|
|
Term
|
Definition
| IL-8, MCP-1, MIP-1alpha, RANTES, eotoxin, lymphotactin |
|
|
Term
|
Definition
| a family of small cytokines or proteins that are characterized by the presence of four cysteine residues in conserved domains that are important in their shape. all function to induce chemotaxis in nearby responsive cells = chemotactic cytokines. attract neutrophils, monocytes, basophils, eosinophils, and lymphocytes to the sites of inflammation. |
|
|
Term
|
Definition
| chemotactic for neutrophils |
|
|
Term
|
Definition
| Regulated upon Activation, Normal T cell Expressed and Secreted. released by CTLs and is a potent chemoattractant factor for monocytes and T cells. |
|
|
Term
|
Definition
| rapidly synthesized by endothelial cells and activated macrophages. local mediator for vasodilation, reduced leukocyte adhesion, reduced platelet adhesion. together with ROS can kill bacteria. see diagram p. 18 |
|
|
Term
| histologic landmark of acute inflammation |
|
Definition
| emigration of leukocytes (neutrophils, then macrophages) to the site of injury or infection |
|
|
Term
| etiologic agents of acute inflammation (5) |
|
Definition
| microorganisms (bacteria), physical agents (burns, radiation, trauma), chemical agents and microbial toxins, necrotic tissue, immunologic reactions (Ag-Ab complexes) |
|
|
Term
| stages of acute inflammation (3) |
|
Definition
| vascular changes, cellular responses: leukocyte recruitment and activation, resolution or repair |
|
|
Term
| vascular changes in acute inflammation (4) |
|
Definition
| vasodilation and increased blood flow, increased vascular permeability (edema) due to leakage of fluid and increased hydrostatic pressure, slowing of blood flow (stasis) due to increased viscosity, margination of leukocytes |
|
|
Term
| cellular responses (leukocyte recruitment and activation) in acute inflammation (4) |
|
Definition
| adhesion and transmigration, chemotaxis, activation, phagocytosis and killing |
|
|
Term
| what makes dilation of blood vessels remarkable in acute inflammation? |
|
Definition
| they are capillaries, so don't dilate and contract due to smooth muscle |
|
|
Term
|
Definition
| the unidirectional movement of cells along a chemical gradient (in the interstitium) |
|
|
Term
| heat and redness at sites of acute inflammation |
|
Definition
| = vasodilation and increased blood flow |
|
|
Term
| key mediators of vasodilation (3) |
|
Definition
| prostaglandins, histamine, NO |
|
|
Term
|
Definition
| = increased vascular permeability > accumulation of protein-rich fluid in the interstitium |
|
|
Term
| key mediators of increased vascular permeability (5) |
|
Definition
| histamine, bradykinin, C3a/5a, leukotrienes, PAF |
|
|
Term
| key mediators of pain (2) |
|
Definition
| bradykinin, prostaglandins |
|
|
Term
| defects in cellular responses in acute inflammation (3) |
|
Definition
| acquired - diabetes, alcoholism. congenital - rare. |
|
|
Term
| adhesion and transmigration (3) |
|
Definition
| attracting leukocytes and delivering them into the surrounding tissue. = extravasation: 1. margination, rolling and adhesion 2. transmigration or diapedesis, 3. migration in the interstitial tissues along a chemotactic gradient |
|
|
Term
|
Definition
| after rolling they enter a high-affinity state and bind to the integrin ligand (ICAM-1) on the vessel endothelium. = adhesion |
|
|
Term
|
Definition
| CD31 = protein on leukocyte that helps diapedesis, PECAM-1 = protein in the intercellular endothelial junction that helps diapedesis |
|
|
Term
| slowing of blood flow in dilated vessels causes |
|
Definition
| stasis and margination of leukocytes on the surface of endothelial cells |
|
|
Term
|
Definition
| stuff on endothelium that allows rolling of leukocytes on endothelium |
|
|
Term
|
Definition
| receptors on leukocytes - bind the selectins on the endothelium to permit rolling |
|
|
Term
| P-selectin is re-distributed to the surface of endothelial cells by (3) / how long does this take |
|
Definition
| local inflammatory mediators - histamine, thrombin and PAF / this occurs within minutes |
|
|
Term
| cytokines (IL-1 and TNF-alpha) are synthesized by macrophages when? and _ are released locally by macrophages, mast cells, and endothelial cells activated by cytokines. |
|
Definition
| after 1-2 hours into acute inflammation. / chemokines |
|
|
Term
| cytokines upregulate expression of |
|
Definition
| E-selectin, ICAM-1 = endothelial cell adhesion molecules |
|
|
Term
|
Definition
| promote firm adhesion by making integrins high affinity (increasing the avidity of integrins). promote transmigration. |
|
|
Term
|
Definition
| involves binding of CD31 on leukocytes to PECAM-1 in the intercellular junction. leukocytes secrete proteases locally to facilitate their migration across the basement membrane and into the extravascular CT. |
|
|
Term
| most important chemotactic factors in acute inflammation (3) |
|
Definition
| C5a/leukotriene B4, chemokines (IL8, MCP-1), bacterial products (N-formyl-methionyl peptides) |
|
|
Term
| general timeline of first three days of acute inflammation |
|
Definition
| edema peaks halfway through day 1. neutrophils peak at day 1. monocytes/macrophages peak at day 2 and make the transition to wound healing |
|
|
Term
| leukocyte activation is triggered by |
|
Definition
| binding of ligands to surface receptors of inflammatory cells. then production of ROS and phagocytosis of microbe into phagosome activates leukocytes. |
|
|
Term
|
Definition
| creates an influx of calcium |
|
|
Term
| see diagram on p. 25 of inflammation |
|
Definition
|
|
Term
| when microbe is phagocytosed, what happens |
|
Definition
| it fuses with a lysosome, where the acidic pH starts breaking it down. then ROIs and NO kill it. |
|
|
Term
| chronic granulomatous disease |
|
Definition
| when NO/ROIs don't kill the microbe after it is phagocytosed and fuses with a lysosome |
|
|
Term
| 2 mechanisms used to kill bacteria |
|
Definition
| oxygen-dependent and oxygen-independent |
|
|
Term
| oxygen-dependent bacteria killing |
|
Definition
| external COX > free radical within phagocytic vacuole |
|
|
Term
| oxygen-independent bacteria killing (5) |
|
Definition
| lysozyme, lactoferrin, bacterial permeability protein, major basic protein (eosinophils), defensins >>> make pores for lysis. |
|
|
Term
| after microbes are killed, they are degraded by |
|
Definition
| acidic hydrolases within phagolysosomes |
|
|
Term
| what has potential to damage host tissue? (4) |
|
Definition
| proteases, lysosomal enzymes, reactive oxygen metabolites and NO released from leukocytes |
|
|
Term
|
Definition
| dead tissue, dead neutrophils, and dead bacteria producing pus |
|
|
Term
| termination of acute inflammation (3) |
|
Definition
| breakdown of chemical mediators, restoration of normal vascular permeability, synthesis and release of endogenous anti-inflammatory agents |
|
|
Term
| endogenous anti-inflammatory agents (3) |
|
Definition
| lipoxins (arachidonic acid metabolites released by macrophages in late stages of inflammation), IL-10 (cytokine), TGF-beta (transforming growth factor beta) |
|
|
Term
| tissue damage is healed by |
|
Definition
| regeneration if CT framework remains intact; fibrosis or scarring in organs that cannot regenerate |
|
|
Term
| acute bacterial pneumonia |
|
Definition
| edema, accumulation of neutrophils in alveolar spaces |
|
|
Term
| key mediators responsible for acute inflammation? (7) |
|
Definition
| vasodilation, increased vascular permeability, chemotaxis, and leukocyte activation, pain, fever, tissue damage |
|
|
Term
| defects in leukocyte adhesion |
|
Definition
| (integrins LFA-1 and Mac-1 or sialyl-lewis x) > repeated bacterial childhood infections |
|
|
Term
| defects in leukocyte killing |
|
Definition
| (deficiency in NADPH oxidase subunits) > severe infections that do not resolve and cause granulomas (chronic granulomatous disease) |
|
|
Term
| defects in phagolysosome fusion |
|
Definition
| impaired innate and acquired immunity (Chediak-Higashi syndrome) |
|
|
Term
| acquired defects in acute inflammation (4) |
|
Definition
| secondary to chemo, diabetes, malnutrition, sepsis (severe systemic inflammation) |
|
|
Term
| excess fluid and dead neutrophils and stuff is cleaned by |
|
Definition
|
|
Term
| (2) cause fibrosis instead of resolution. t/f acute bacterial pneumonia resolves instead of fibroses |
|
Definition
| abscess, chronic inflammation / true |
|
|
Term
| acute inflammation is effective against (2) |
|
Definition
| extracellular bacteria, lytic viruses |
|
|
Term
| microorganisms that do not elicit acute inflammation / are controlled by |
|
Definition
| intracellular bacteria, non-lytic or persistent viruses / granulomatous inflammation |
|
|
Term
| normal functions of macrophages (3) |
|
Definition
| daily housekeeping (soot in lungs), cleaning up cell debris, killing microorganisms |
|
|
Term
|
Definition
| dust cells, osteoclasts, kupffer cells, microglia |
|
|
Term
|
Definition
| bigger, more diffuse contents and feet coming out. increased metabolic activity and lysosomal enzymes |
|
|
Term
| what activates macrophages |
|
Definition
| cytokine IFN gamma from activated T cell; also innate immunity like endotoxin, fibronectin, chemical mediators (TNF alpha) |
|
|
Term
|
Definition
| cluster or aggregate of activated macrophages (multinucleated giant cells) |
|
|
Term
| activated macrophages screte a range of cytokines (5) |
|
Definition
| IL1beta, TNFa, IL6, CXCL8, IL12 |
|
|
Term
|
Definition
| activates NK cells, induces the differentiation of CD4 t cells into TH1 cells |
|
|
Term
|
Definition
| chemotactic factor recruits neutrophils, basophils, and t cells to site of infection |
|
|
Term
|
Definition
| lymphocyte activation, increased antibody production > fever and systemic acute-phase protein production |
|
|
Term
|
Definition
| increases vascular permeability and activates endothelium > 1. increased entry of IgG, complement, and cells to tissues and 2. increased fluid drainage to lymph nodes >> fever, shock, mobilization of metabolites |
|
|
Term
|
Definition
| activates vascular endothelium, activates lymphocytes, local tissue destruction increases access of effector cells >>> fever + production of IL6 (>antibodies) |
|
|
Term
| common properties of etiologic agents of granulomatous inflammation |
|
Definition
| foreign or endogenous materials that are poorly degradable, irritating, and persistent in the body for several weeks up to many years |
|
|
Term
| granulomatous inflammation is frequently potentiated by |
|
Definition
| an immune response to the stimulus, usually cell-mediated immunity |
|
|
Term
| examples of etiologic agents of granulomatous inflammation (5) |
|
Definition
| sutures (exogenous), keratin/lipids (endogenous materials), antigenic exogenous metals (beryllium), infectious agents (MYCOBACTERIUM TUBERCULOSIS), sarcoidosis (mechanism unknown) |
|
|
Term
|
Definition
| infection with mycobacterium tb |
|
|
Term
| host defenses against mycobacteria include (7) |
|
Definition
| TNF, IFN gamma, ROS, NO, Th1 (CD4 + T lymphocytes), activated macrophages. LOTS OF DESTRUCTION |
|
|
Term
| why don't dust cells kill mycobacteria |
|
Definition
| because they replicate within the phagosomes. phagosomes spread through lymph to blodd to spleen, marrow etc. = bacteremia |
|
|
Term
| what causes tuberculin positivity (hypersensitivity) |
|
Definition
|
|
Term
| in granulomatous inflammation, infected macrophages produce / what kills mycobacteria |
|
Definition
| cytokines to recruit t cells > Th1 release cytokines to activate infected macrophages: free radicals and NO help to kill mycobacteria |
|
|
Term
|
Definition
| histologic appearance of NO, ROS and TNF all killing the infected macrophages in TB (lungs+kidneys) |
|
|
Term
|
Definition
| the immune system is succesfful and the infection remains latent |
|
|
Term
|
Definition
| nodules of healed, fibrosed, calcified granulomas. can be detected on chest xray. |
|
|
Term
|
Definition
| drug to treat TB through TNF response. (doesn't work if you have rheumatoid arthritis and are taking anti-TNF meds) |
|
|
Term
|
Definition
|
|
Term
|
Definition
| sub-saharan africa, SE asia, western pacific |
|
|
Term
| if you get a positive PPD test, what are the next steps in diagnosing TB? |
|
Definition
| use PCR machine with your spit. takes less than 2 hours |
|
|
Term
| host factors that favor reactivation or reinfection of TB (4) |
|
Definition
| HIV, exogenous corticosteroids, advanced age, malnutrition |
|
|
Term
|
Definition
| caused by massive hematogenous dissemination = progressive primary or secondary tb with low immunity. (spleen and liver) |
|
|
Term
| hallmark of CHRONIC inflammation |
|
Definition
| dense infiltration of tissues with lymphocytes, plasma cells, and macrophages. |
|
|
Term
| reciprocal interaction between lymphocytes and macrophages that prolong their activation (in chronic inflammation) via |
|
Definition
| release of INF gamma and IL 12, respectively |
|
|
Term
| "alternatively activated" macrophages in chronic inflammation (M2) release |
|
Definition
| TGF beta and other mediators that stimulate fibrosis |
|
|
