Cell Events in Acute Inflammation & Outcomes Flashcards
Vasoactive Amines
- Preformed molecs in granules
- Se from platelets
- His from mast cells & other cells
- physical trauma or heat
- IgE on mast cells
- complement C3a, C5a
- leukocyte derived his releasing proteins
- neuro peptides substance P
- IL-1, IL-8
Arachidonic Acid metabolites
- vasodilation- PGI2, PGE1, PGE2, PGD2
- vasoconstriction- Thromboxane A2, leukotrienes C4,D4,E4
- increased vascular permeability- leukotrienes C4,D4,E4
- Chemotaxis, leukocyte adhesion- luekotriene B4
PAF
- mem phospholipid derived mediator
- aggregate platelets & cause degranulation
- acetyl glycerol ether phosophrylcholine
- from neutrophils, monocytes, basophils, endoth cells, & platelets
- acts on GPCR
- vasoconstriction & bronchoconstriction
- 100-1000 more potent than his in inducing vasodilation & increase vascular perm
- enhanced leukocyte adhesion, chemotaxis, leukocyte degranulation & ox burst
- stimulates syn of eicosanoids
ROS
- NADPH oxidase pathway makes it
- from neutrophils & macrophages when killing microbes, immune omplexes, cytokines & other inflamm stimuli
- ROS are produced w/in lysosomes to destroy microbes & necrotic cells
- Increase chemokine, cytokine & adhesion molec expression= amplify cascade of inflamm mediators
ROS
@ higher levels
- endoth damage w/ thrombosis & increased perm
- protease activation & antiprotease inactivation, breakdown of ECM
- direct injury to cells like tumor cells, RBCs, parenchymal cells
- antiox protective mech in place= catalase, SOD, glutathione
NO
- regulate NT release in CNS
- macrophage-cytotoxic metabolite against microbes & tumor cells
- endoth cells it causes smooth m. relaxation & vasodilation
- NO syn from L- arg, O2 & NADPH by NOS
NO 3 isoforms
- type I nNOS- constitutively expressed neuronal NOS
- type II iNOS- inducible enz present in macrophages & endoth cells, induced inflamm cytokines & mediators (IL-1, TNF, IFN-g) & bac endotoxin.
- Type III eNOS- constitutively syn NOS found w/in endothelium
NO
Cytokines
- Polypep products of many cell types that f as mediators
- some stim bone marrow precursors to produce more leukocytes
- interleukins b/c mediate b/t leukocytes
- Many act on leukocytes but not call ILs
- TNF, IL- & chemokines= acute inflammation
- IFN-g & IL-2 in **chronic inflammation **
TNF
Found in macrophages, mast cells, T lymph
Action:
- stim expression of endoth adhesion molec
- secretion of other cytokines
- systemic effects!
- acute inflamm
IL-1
Found in macrophages, endoth cells, epith cells (some)
Action:
- similar to TNF
- greater role in fever
- acute inflamm
Chemokines
Found in macrophages, endoth cells, T lymph, mast cells, other cell types
- recruite leukocytes to sites of inflamm
- migration of cells to normal tissues
- acute inflamm
IL-6
Found in macrophgaes, other cells
- produce systemic effects
- acute inflamm
IL-12
found in dendritic cells, macrophages
Action:
- increae IFN-g production
- chronic inflamm
IFN-g
Found in T lymph, NK cells
Action:
- activation of macrophges (increased killing of microbes & tumor cells)
- chronic inflamm
IL-17
Found in T lymphocytes
Action:
- recruit of neutrophils & monocytes
- chronic inflamm
Chemokines
- small protein- chemo attractant
- leukocyte recruitemnt in inflamm & other cells in lymphoid & other tissues
- activate leukocytes
- produced constitutively in tissues & responsible for T & B lymphocyte segregation in diff areas of LN & spleen
- mediate via GPCR
- CXCR4 & CCR5 are coR for binding & entry of HIV into lymphocytes
Lysosomal Enz of Leukocytes
- neutrophils & monocytes lysosomal granules release molecs
- acid protease pH optima limit activity only w/in phagolysosomes
- neutral protease- elastase, collagenase & cathepsin. Active in ECM & degrade matrix proteins
- Neutral Protease cleaves complement proteins directly to generate C3a & C5a & directly generate bradykinin from kininogen
Antiprotease check damaging effects of lyssomal enz
- a1 antitrypsin- major I of neutrophil elastase & a2 macroglobulin
- deficiencies of these inhibitors leads to tissue destruction @ sties of luekocyte accumulation
- a1 antitrypsin def in lung can cause sever panacinar emphysema
Neuropeptides
- substance P, transmit pain signals, reg vessel tone & modulate vascular perm
- n. fibers secrete neuropeptides prominent in lung & GI
Complement Sys
- Found in plasma
- produced in liver
action:
- leukocyte chemotaxis, activation, opsonization
- vasodilation
Bradykinin
- found in plasma
- produced in liver
action:
- increased vascular perm
- smooth m. contraction
- vasodilation
- pain
Proteases activated during coagulation
- found in plasma
- produced in liver
action
- endoth activation
- leukoyte recruitment
Complement
Complement
- complement prot present in circulation
- classic pathway when Igs are attached
- Cascade generates C3b which acts like opsonin or C5a (neutrophil attractant)
- C5-9 complex is known as Mem Attack Complex MAC
- When MAC attaches, lysis by perforation of cell mem
Alternate Pathway
- Generate C3b oR C5a via bacterial products
- NOT Ig mediated
- Still create MAC & lyse cell mem by perforation
Clotting Cascade
Phagocytosis & clearance
Acute inflammation
- resolution
- exudate- serous, fibrinous, purulent
- suppurative inflamm
- abscess
- ulcer
*neutrophils at first
Serous exudate
sqamous mucosa separated from dermis
2nd degree burn blister
Serous exudate pleural effusion
Fibrinous exudate
contains fibrin
fibrinous pericarditis w/ strangs of fibrin b/t visceral & pareital pericardiaum
Bread & butter pericarditis of uremia
Fibrinous exudate
fibrinous pericarditis- uremia
Purulent Pericardial Effusion
Purulent Ascites Abdomen
Purulent exidate inflammation
acute bacterial meningitis
Acute meningitis
Acute bronchopneumonia
Acute Bronchopneumonia
Bronchopneumonia
productive cough- large amts of purulent sputum
suppurative inflamm (w/ pus)
G+ cocci in pneumonia gram stain
Abscess
localized collection of pus
liquefactive necrosis of abascess is apparent b/c purulent contents are draining out to leave a cavity
Acute Pneumonia Abscess formation
loss of alveolar spaces & liquefactive necrosis
acute inflammation ulcer
local mucosal defect of surface of organ or tissue
produced by sloughing of necrotic tissue
Found in an ulcer base:
- fibrin
- neutrophils
- active granulation tissue
- collagen
Gastric ulcer
Gastric ulcer micro
Skin Ulcer
Cardinal Signs of Inflammation
- red- hyperemia (increase BF) & vasodilation (his, PG, NO)
- PAIN- swelling from stretch sensory R & inflamm mediators
- heat- increased BF to body periph
- swelling- due to his, SE, C3a & 5a, bradykinin, leukotrienes, PAF, SP
- loss of f- from mech/structural necrosis or healing
