Term
|
Definition
| nonspecific cellu;ar & molecular rxn to injury of vascularized tissue, beneficial in intent, and also potentially damaging to the host |
|
|
Term
| What are the 2 types of inflammation? |
|
Definition
|
|
Term
When does acute inflammation occur as opposed to chronic?
How long do they persist for? |
|
Definition
acute: soon after injury & resolves relatively quickly
chronic: after prolonged injurous event & persists in the tissue |
|
|
Term
| When do leukocytes infiltrate in acute inflammation? |
|
Definition
| after initial vascular response |
|
|
Term
| How is leukocyte infiltration different in actue & chronic inflammation? |
|
Definition
acute: neutrophils first, then monocytes => macrophages
chronic: macrophages, lymphocytes & plasma cells |
|
|
Term
|
Definition
| rubor, tumor, calor, & dolor |
|
|
Term
| What happens to vasculature in acute inflammation? |
|
Definition
| dilation & increased permeability |
|
|
Term
| When does tissue repair occur? |
|
Definition
| With inflammation, but usually finishes after inflammation has gone |
|
|
Term
| What is included in tissue repair? |
|
Definition
1) regeneration of injured cells
2) formation of scar tissue |
|
|
Term
| What occurs as a result of vasodilation + increased vascular permeability in acute inflammation? |
|
Definition
| increased extravascular fluid with high protein content (edema) & intravascular stasis of blood (increased pressure) |
|
|
Term
| What mediates vasodilation in acute inflammation? |
|
Definition
| chemical mediators (histamine, NO) |
|
|
Term
| What are the 4 pathogenic mechaniss of increased vascular permeability in acute inflammation? |
|
Definition
1)*formation of gaps b/w endothelial cells of venules
2)injury to endothelium of microcirculation
3) increased endothelial transcytosis
4) secondary to angiogenesis (repair) |
|
|
Term
| How long can gap formation b/w endothelial cells of venules last? |
|
Definition
delayed, longer lasting response
immediate transient response |
|
|
Term
| What causes delayed, longer lasting response gap formation b/w venule endothelial cells? |
|
Definition
| cytoskeletal changes of endothelium resulting in retraction |
|
|
Term
| What causes immediate transient response gap formation b/w venule endothelial cells? |
|
Definition
| endothelial cell contraction (retraction) |
|
|
Term
| What can cause injury to endothelium of microcirculation? |
|
Definition
1) bacterial toxins, tissue necrosis, cell damage of some type, etc
2) activated leukocytes |
|
|
Term
| What causes increased edothelial transcytosis? |
|
Definition
| changes in the cytoplasmic vesiculovacuolar channels |
|
|
Term
| What is the most common cause of increased vascular permeability in acute inflammation? |
|
Definition
| retraction of endothelial cells |
|
|
Term
| What is the most common leukocyte response in acute inflammation? |
|
Definition
| neutrophils for 1st 2 days & then monocytes |
|
|
Term
| *What in acute inflammation leads to leukocyte margination, rolling, adhesion, diapedesis, chemotaxis, activsation, phagocytosis & release of toxic products? |
|
Definition
| intravascular stasis of blood |
|
|
Term
| How does stasis or blood promote margination of WBCs & leukocytes? |
|
Definition
| disrupts normal axial flow |
|
|
Term
|
Definition
| low-affinity, transient attachment of leukocytes to endothelium via interaction b/w selectins & their ligands |
|
|
Term
| What promotes/mediates rolling of leukocytes in inflammation? |
|
Definition
| chemical mediators released in response to injury promote increased expression of P- & E- selectins on endothelial cell surface => weakly bind to ligands on leukocyte, WBC cell membrane => transient attachement (rolling) |
|
|
Term
|
Definition
| high affinity, firm attachment of leukocytes to endothelium b/w integrins & lignads |
|
|
Term
| What promotes/mediates adhesion of leuokocytes in inflammation? |
|
Definition
on endothelium: various cytokines => increased integrin ligans on endothelial cell surface
and
on leukocytes: binding of chemokines to endothelial proteoglycans => activation of leukocyte transmembrane integrins to a high-affinity state |
|
|
Term
| What promotes diapedesis of leukocytes in inflammation after adhesion? |
|
Definition
| chemokine response => migration b/w endothelial cells thru basement membrane & into extravascular CT matrix |
|
|
Term
| What in the intracellular junctions of endothelial cells has a role in diapedesis? |
|
Definition
|
|
Term
| What is secreted to promote diapedesis thru the basement membrane of endothelial cells? |
|
Definition
|
|
Term
| When in diapedesis are leukocyte adhesion molecules required again? |
|
Definition
| in the extravascular CT matrix |
|
|
Term
|
Definition
| movement in response to a chemical gradient |
|
|
Term
| How do chemotactic agents (exogenous & endogenous) cause contraction of the filopodium (i.e. causing leukocytes to move)? |
|
Definition
| chemotactic agents bind leukocyte G protein coupled receptors => cellular activation => actin reoganization => regulated interaction b/w polymerized actin & myosin => contraction of filopodium |
|
|
Term
| What causes cellular activation? |
|
Definition
| binding of receptors to various ligands => cellular modifications |
|
|
Term
| What do TLRs (toll-like receptors) bind to cause cellular activation? |
|
Definition
| microbial products s.a. LPS |
|
|
Term
| What do G protein coupled receptors bind to cause cellular activation? |
|
Definition
| substances s.a bacterial peptides, chemokines, C5a, arachidonic acid metabolites |
|
|
Term
| What do receptors for cytokines bind to cause cellular activation? |
|
Definition
|
|
Term
| What do receptors for opsonins bind to cause cellular activation? |
|
Definition
| substances s.a. IgG, C3b, certain plasma lectins |
|
|
Term
| What are the 2 consequences of cellular activation? |
|
Definition
1) amplification of inflammatory response
2) initiation of phagocytosis with release of toxic products |
|
|
Term
| What increases phagocytosis? |
|
Definition
|
|
Term
| How are items recognized for phagocytosis? |
|
Definition
|
|
Term
| What needs to be modified in order for engulfment to occur? |
|
Definition
| cytoskeletal & cell membrane modifications |
|
|
Term
| How does engulfment occur? |
|
Definition
| cytoplasmic pseudopods surround particle => formation of phagosome => fusion with lysosome => degranulation into resultant phagolysosome |
|
|
Term
| What are the 2 mechanisms of cellular killing? |
|
Definition
*oxygen dependent
oxygen-independent |
|
|
Term
def
*oxygen-dependent killing mechanism |
|
Definition
activation of NADPH oxidase in phagolysosomal membrane => formation of surperoxide anion => formation of hydrogen peroxide =>
a) hydroxyl free radical
b) hypochlorite (when myeloperoxidase is combined with a halide) |
|
|
Term
def
oxygen independent killing |
|
Definition
| proteins in leukocyte granules s.a. bactericidal premeability increasing protein, enzymes, lactoferrin, etc |
|
|
Term
| How does degradation occur after killing? |
|
Definition
| lysosomal acid hydrolysis |
|
|
Term
| Where are 2 places toxic products can be released to? |
|
Definition
1) phagolysosome
2) extracellular tissue |
|
|
Term
| What are the 3 ways toxic products are released to the extracellular tissue? |
|
Definition
1)regurgiation during feeding
2)frustrated phagocytosis
3)cytotoxic release |
|
|
Term
| What causes termination of acute inflammation? |
|
Definition
| removal of initial stimulus, short-lived chemical mediators, apoptosis of neutrophils, & production/release of various agents (anti-inflammatories) |
|
|
Term
| What are the 5 sources of chemical mediators of acute inflammation? |
|
Definition
1) preformed cellular stores
2) plasma proteins
3) newly synthesized cellular products
4) phagolysosome components of activated leukocytes
5) other pro-inflammatory mediators |
|
|
Term
| What source of chemical mediation of acute inflammation are the early responders? |
|
Definition
| preformed cellular stores |
|
|
Term
| What do the preformed cellular stores chemical mediators of acute inflammation consist of? |
|
Definition
*vasoactive amines
a) histamine
b) serotonin |
|
|
Term
Function
vasoactive amines |
|
Definition
| vasodilation & increased vascular permeability via endothelial cell contraction |
|
|
Term
| What is the source of histamine as a chemical mediator of acute inflammation? |
|
Definition
| mast cell degranulation triggered via multiple stimuli |
|
|
Term
| What is the source of serotonin as a chemical mediator of acute inflammation? |
|
Definition
|
|
Term
| How are plasma proteins chemical mediators of acute inflammation? |
|
Definition
| they're inactive precursors |
|
|
Term
| What happens when plasma protein precursors of chemical mediators of acute inflammation are activated? |
|
Definition
| they regulate systems of enzymatic cascades to amplify the inflammatory response |
|
|
Term
| What are the 3 systems of plasma protein chemical mediators of acute inflammation (i.e. cascades that amplify acute inflammatory response)? |
|
Definition
1) complement system
2) kinin system
3) coagulation systems |
|
|
Term
| What are the 3 pathways of activation of the complement cascade? |
|
Definition
classical, alternative, or lectin pathways
(also C3 & C5 can be activated via proteolytic enzymes within inflammatory exudate) |
|
|
Term
| How is the classical complement system activation? |
|
Definition
| C1 fixation to Ag-Ab complex |
|
|
Term
| How is the alternative complement system activated? |
|
Definition
| direct activation by microbial products |
|
|
Term
| How is the lectin complement pathway activated? |
|
Definition
| C1 activation via plasma lectin binding to microbial sugars |
|
|
Term
| Where do all 3 complement pathways coverge? (i.e. what step is the same) |
|
Definition
| formation of C3 covertases to cleave C3 |
|
|
Term
| What happens when C3 is cleaved? |
|
Definition
| release of C3a & binding of C3b |
|
|
Term
| What is formed once C3b binds? |
|
Definition
| C5 convertases to cleave C5 |
|
|
Term
| What happens when C5 is cleaved? |
|
Definition
| release of C5a & binding of C5b |
|
|
Term
| What happens ince C5b binds? |
|
Definition
| C6-C9 follow the same formation => formation of membrane attack complex (MAC) to form pores |
|
|
Term
| What are the 4 major effects of the activated complement system? |
|
Definition
1) vasodilation & increased vascular permeability (via C3a & C5a => stimulate mast cell degranulations => histamine release)
2) leukocyte chemotaxis & activation (via C5a)
3) opsonization (via C3b) => phagocytosis
4) cell lysis (via MAC) |
|
|
Term
| What activated the kinin system? |
|
Definition
| contact of factor XII (hageman factor) |
|
|
Term
| What does activation of factor XII cause? |
|
Definition
| production of factor XIIa |
|
|
Term
| What does factor XIIa cause? |
|
Definition
| coversion of prekallikrein to kallikrein |
|
|
Term
| What does kallikrein cause? |
|
Definition
| proteolytic cleavage of high-molecular wt (HMW) kininogen |
|
|
Term
| What does proteolytic cleavage of HMW kininogen cause? |
|
Definition
|
|
Term
| What are the 3 major effects of activation of the kinin pathway? |
|
Definition
1) HMW kininogen & kallikrein => increased XII activation
2) kallikrein => chemotaxis & generation of plasmin
3) bradykinin => vasodilation, increased vascular permeability & pain |
|
|
Term
| What 2 systems are coagulations systems? |
|
Definition
1) clotting system
2) fibrinolytic system |
|
|
Term
| What 2 pathways converge in the clotting system? |
|
Definition
| interconnected intrinsic & extrinsic pathways |
|
|
Term
| What plays a key role in the clotting system? |
|
Definition
|
|
Term
| What is thrombin generated from? |
|
Definition
| prothrombin near the end of the coagulation cascade that results in fibrin formation |
|
|
Term
| What does thrombin bind to in the clotting system? |
|
Definition
| protease-activated receptors (g protein coupled receptors) on many cells |
|
|
Term
| What does thrombin binding cause in the clotting system? |
|
Definition
| increased inflammatory response |
|
|
Term
| What plays a key role in the fibrinolytic system? |
|
Definition
|
|
Term
|
Definition
| cleavage of plasminogen by plasminogen activator |
|
|
Term
| What does plasmin formation cause? |
|
Definition
| increased inflammatory response |
|
|
Term
| What are the 4 newly synthesized chemical mediators of acute inflammation? |
|
Definition
1) eicosanoids
2) PAF (platelet activating factor)
3) cytokines
4) NO |
|
|
Term
| What eicosanoids are chemical mediators of acute inflammation? |
|
Definition
| arachidonic acid metabolites |
|
|
Term
| What activates arachidonic acid production & release from the cell membrane? |
|
Definition
| mutiple stimuli => increased cytosolic Ca2+ & phospholipase A2 activation |
|
|
Term
| How does arachidonic acid mediate the acute inflammatory response? |
|
Definition
| => metabolic rxns by enzymes => production of mediators to amplify inflammatory response (via G protein coupled receptors) |
|
|
Term
| What arachidonic acid metabolites are synthesized by cyclooxygenases (COX 1 & COX 2) induction? |
|
Definition
| prostaglandins & thromboxane |
|
|
Term
| What is the effect of prostaglandins? |
|
Definition
1) vasodilation, increased vascular permeability, pain, & fever
2) inhibit platelet aggregation |
|
|
Term
| Where is thromobane mainly produced? |
|
Definition
|
|
Term
| What effect does thromboxane have? |
|
Definition
| vasoconstriction & platelet aggregation (opposite effect of prostaglandins) |
|
|
Term
| What arachidonic acid metabolite is synthesized by lipoxygenases? |
|
Definition
|
|
Term
| What happens to metabolite production due to the selective presence of various lipoxygenases in different cell types? |
|
Definition
| can only occur in thru the mutual interation of neutrophils & platelets |
|
|
Term
| What leukotriene is produced mostly by neutrophils? |
|
Definition
|
|
Term
|
Definition
| chemotactic & activated other neutrophils |
|
|
Term
| Function
Leukotrienes: LTC4, LTD4, LTE4 |
|
Definition
| vasoconstriction, bronchospasm & increased vascular permeability |
|
|
Term
|
Definition
| inhibt acute inflammatory leukocyte response |
|
|
Term
| What so anti-inflammatory drugs target? |
|
Definition
| newly-synthetic reactions |
|
|
Term
| What does aspirin & other NSAIDs inhibit? |
|
Definition
| COX (and therefore prostaglandins & thromboxane) |
|
|
Term
| What do steroids inhibit? |
|
Definition
| phospholipase (and therefore all arachidonic acid & it's metabolites) |
|
|
Term
| What is PAF synthesized from? |
|
Definition
|
|
Term
| What leads to PAF production? |
|
Definition
| stimulation of multiple cell types |
|
|
Term
| How does PAF mediate the acute inflammatory response? |
|
Definition
| binds to G protein coupled receptor => increased inflammatory response |
|
|
Term
|
Definition
| secreted proteins that alter the activity of other cell types |
|
|
Term
| What are the 3 cytokines? |
|
Definition
1) TNF (tumor necrosis factor)
2) Interleukins
3) chemokines |
|
|
Term
| What produces TNF & IL-1? |
|
Definition
| macrophages activated at inflammatory sites |
|
|
Term
| What 3 local effects are seen by TNF & IL-1? |
|
Definition
1) leukocyte stimulation (inflammation)
2) endothelial activation (inflammation)
3) stimulation of fibroblasts (repair) |
|
|
Term
| What acute systemic effects are seen by TNF & IL-1? |
|
Definition
| fever, anorexxia, fatigue, increased # circulating neutrophils, APP production, potential hemodynamic alterations |
|
|
Term
| What chronic systemic effects are seen by TNF & IL-1? |
|
Definition
| cachexia (altered metabolic state => wasting) |
|
|
Term
|
Definition
|
|
Term
| What cells secrete chemokines? |
|
Definition
| various cells activated by inflammation |
|
|
Term
| What happens when chemokines bind to their receptors? |
|
Definition
| leukocyte chemotaxis (can be selective) |
|
|
Term
| What increases NO production? |
|
Definition
|
|
Term
| *What 3 actions does NO have? |
|
Definition
1) vasodilation
2) inhibition of inflammation
3) antimicrobial activity |
|
|
Term
| How does NO cause vasodilation? |
|
Definition
| relaxation of vascular smooth muscle |
|
|
Term
| How does NO inhibit inflammation? |
|
Definition
| decrease WBC & platelet adhesion |
|
|
Term
| How does NO have antimicrobial activity? |
|
Definition
|
|
Term
| Why are phagolysosome components of activated leukocytes critical in host defense? |
|
Definition
1) killing &/or degradation of phagocytosed material
2) amplification of inflammatory response |
|
|
Term
What is present in the serum &/or tissue to counteract agents in phagolysosome?
Why are they necessary? |
|
Definition
| essential inactivators (s.a. antiproteases & antioxidants) to protect neiboring cells & ECM |
|
|
Term
| What are the 2 degradative components of phagolysosome of activated leukocytes that can regulate the acute inflammatory response? |
|
Definition
| lysosomal enzymes & oxygen-derived free radicals |
|
|
Term
| *What are the 3 key lysosomal enzymes? |
|
Definition
1) acid hydrolases
2) neutral proteases
3) phospholipase |
|
|
Term
| How are oxygen-derived free radicals formed in the phagolysosome? |
|
Definition
| secondary to NADPH oxidase activation |
|
|
Term
| What are the 3 "other" pro-inflammatory mediators? |
|
Definition
1) neuropeptides
2) hypoxia-induced factor 1α
3) uric acid |
|
|
Term
| Where are neuropeptides (s.a. substance P) produced? |
|
Definition
|
|
Term
| What cells generate hypoxia-induced factor 1α? |
|
Definition
| cells with inadequate oxygen |
|
|
Term
| What is uric acid the end product of? |
|
Definition
|
|
Term
| What is uric acid derived from? |
|
Definition
| breakdown of nucleic acids |
|
|
Term
*Function
thrombin & plasmin |
|
Definition
| amplify multiple steps in the acute inflammatory response |
|
|
Term
|
Definition
| anti-inflammatory function |
|
|
Term
| What 7 chemical mediators of acute inflammatory response are responsible for that vascular changes (vasodilation/increased vascular permeability)? |
|
Definition
| 1) vasoactive amines (preformed histamine & serotonin)
2) anaphylatoxins (C3a & C5a)
3) bradykinin
4) prostaglandins
5) NO (vasodilation only)
6) Leukotrienes (increased vascular permeability only) - except LTB4
7) PAF (increased vascular permeability only) |
|
|
Term
| What 7 chemical mediators of acute inflammatory response are responsible for leukocyte activation? |
|
Definition
| 1) C3b (opsinization)
2) C5a (chemotaxis)
3) LTB4
4) PAF
5) TNF & IL-1
6) chemokines (chemotaxis)
7) lysosomal enzymes & oxygen derived free radicals |
|
|
Term
| What 2 chemical mediators of acute inflammatory response are responsible for platelet activation? |
|
Definition
1) thromoxane (platelet aggregation)
2) PAF |
|
|
Term
| What 2 chemical mediators of acute inflammatory response are responsible for pain? |
|
Definition
1) bardykinin
2) prostaglandins |
|
|
Term
| What 2 chemical mediators of acute inflammatory response are responsible for tissue destruction? |
|
Definition
1) lysosomal enzymes
2) oxygen derived free radicals |
|
|
Term
| What 2 chemical mediators of acute inflammatory response cause systemic effects? |
|
Definition
1) prostaglandins (fever)
2) TNF & IL-1 |
|
|
Term
| *How do small lymphatics eventually drain into the systemic venous circulation? |
|
Definition
| Sm. peripheral thin-walled lyphatic capillaries => larger lyphatic vessels w/ one-way valves => filtration thru lymph nodes => eventual drainage |
|
|
Term
| Why are lymphatics important in acute inflammation? |
|
Definition
| it's a potential source for dissemination of initially local processes |
|
|
Term
| What 2 roles (besides potential dissemination route) does lymphatics have in acute inflammation? |
|
Definition
1) clearance of excess interstitial fluid (edema)
2) enhancement of host response by adaptive & mononuclear phagocytic systems |
|
|
Term
| How do lymphatics cause enhancement of hose response by adaptive imune & mononuclear phagocytic systems? |
|
Definition
| exposure of Ag, Ag processing cells & activated lymphocytes drained from injured site to lymph nodes |
|
|
Term
| *What are the consquences of acute inflammation dependent on? |
|
Definition
| severity, duration & site of inciting stimulus and effectiveness of host inflammatory response |
|
|
Term
| What are the 3 potential consequences of acute inflammation? |
|
Definition
1) complete resolution
2) healthing with fibrosis
3) persistent inflammation |
|
|
Term
|
Definition
| restoration of tissue back to normal morphology & function |
|
|
Term
| What causes healing with fibrosis? (scarring?) |
|
Definition
| more significant tissue damage, as well as sites with limited regeneration |
|
|
Term
| What are the 4 distinctive variations of acute inflammation? |
|
Definition
1) Serous inflammation
2) fibrinous inflammation
3) suppurative (purulent) inflammation
4) ulceration |
|
|
Term
|
Definition
| responsed to injury characterized predominately by an accumulation of sparsely cellular fluid (i.e. superficial burn, blister) |
|
|
Term
def
fibrinous inflammation |
|
Definition
| an acute inflammatory response process in which extravascular fibrin deposition plays a prominent role (esp. on tissue surfaces within body cavities) |
|
|
Term
def
suppurative (purulent) inflammation |
|
Definition
| dense collection of acture inflammatory cells with accomplanying proteinaceous edema fluid and necrotic cellular debris (exudate) |
|
|
Term
| What often causes suppurative (purulent) inflammation? |
|
Definition
|
|
Term
| What type of suppurative inflammation is in its own distinctive category? |
|
Definition
|
|
Term
|
Definition
| focal accumulation of suppurative inflammation within an organ that destroys the resident tissue => liquefactive necrosis |
|
|
Term
| What surround abcess if it's long lasting? |
|
Definition
|
|
Term
|
Definition
| erosion of an organ's epithelial surface & subjacent tissue dur to shedding of necrotic cells & debris, accompanied by an acute inflammatory exudate |
|
|
Term
| What happens in ulceration is long-standing? |
|
Definition
| chronic inflammation & fibrosis develop at the base |
|
|
Term
| What causes realease of acute inflammatory mediators? |
|
Definition
|
|
Term
| What do inflammatory mediators promote in the inflammatory response? |
|
Definition
| vasodilation & increased vascular permeability => influx & activation of acute inflammatory cells (neutrophils & macrophages) |
|
|
Term
| What does activation of inflammatory cells lead to? |
|
Definition
| dilution/phagocytosis of initiating insult & amplification of the inflammatory response (via formation of additional mediators) => 1 of 3 consequences of acute inflammation |
|
|
Term
| What are the 7 vascular mediators in acute inflammation? |
|
Definition
1) Prostaglandins
2) Leukotrienes (C,D,E)
3) Anaphlatoxins (C3a, C5a)
4) NO
5) Bradykinin
6) PAF
7) Vasoactive amines (serotonin & histamine)
(PLAN BP Vasodilation - and every other letter starting with L does NOT do BOTH vasodilation & increase permeability)
Leukotrienes C,D,E (C=vasoConstrict therefore vascular permeability)
NO (vasodilation only)
PAF (vascular permeability) |
|
|
Term
| What are the 7 leukocyte mediators of acute inflammation? |
|
Definition
1) Chemokines (chemotactant)
2) C5a (chemotactant)
3) C3b (Obsonization)
4) Leukotriene B
5) Lysosomal enzymes/Oxygen free radicals
6) IL-1/TNP
7) PAF
(CCCLLIP - you clip things on)
*notice PAF is the past P for both PLAN BP Vasodilation & CCCLLIP |
|
|
