inflammation Flashcards
____, ____, and _____ are due to vascular changes; ____ and _____ are due to chemical mediators and infiltration of leukocytes
heat (calor); redness (rubor); swelling (tumor)
pain (dolor); loss of function
acute inflammation is characterized by ____ and ____
exudation (emitting fluid); neutrophil infiltration
chronic inflammation is characterized by _____ with _____ and _____ in later stages
mononuclear inflammatory cell infiltration (lymphocytes, macrophages, plasma cells); vascular proliferation; fibrosis
fever is mediated by:
IL-1, TNF, and PGE2
vascular changes in acute inflammation include _____ and ______
vasodilation; increased vascular permeability
vasodilation is mediated by endothelial cell release of ____ which induces vascular smooth muscle relaxation and _____ release of ____; vasodilation is maintained by ______
NO; mast cell; histamine; prostaglandins (PGI2, PGD2, PGE2, and PGF2)
vasodilation beings in the _____ and results in engorgement of ______
pre-capillary arterioles; capillary beds
movement of inflammatory cells out of the vessels (bc of increased vascular permeability), called ____, occurs at the level of _____
diapedesis; post-capillary venules
transudate usually accumulates due to _____ (due to ______) and/or _____
increased hydrostatic pressure (usually due to reduced venous return); decreased serum oncotic pressure
exudate is indicative of ____ and _____ damage
tissue; endothelial cell
increased vascular permeability may be due to _____ or ____ to the endothelial cells
inflammatory mediators; direct injury
endothelial cell contraction forms _____ (mainly in ______) due to reversible contraction; occurs rapidly and lasts for 15-30 min
intercellular gaps; post-capillary venules
endothelial cell contraction is mediated by ____ and ____ early, and later on by ____ and _____; ____ and ____ induce vasoactive amine release which leads to edema
histamine; bradykinin; leukotrienes; PAF; C3a and C5a
endothelial cell retraction due to ____ of _____ is mediated by _____; takes 4 to 6 hours to develop and lasts for 24 hours or more
restructuring; cytoskeletal proteins; IL-1, TNF, and IFNgamma
direct venule endothelial cell injury may occur from _____ of _____ and ______ during the inflammatory response
neutrophilic release of ROS and lysosomal enzymes (proteases)
3 cellular changes during inflammation
- endothelial cell activation
- leukocyte extravasation
- leukocyte activation/phagocytosis
factors that will activate endothelial cells
histamine, thrombin, complement factors, cytokines (IL-1, TNF), bacterial products, hypoxia, viruses, PAF
activated ECs are characterized by production of ___ and ___ that induce vasodilation, ____, rearrangement of cytoskeletal proteins leading to ____, increased expression and affinity of _____, and synthesis and release of ____
PGI2; NO contraction/retraction retraction surface cell adhesion molecules inflammatory mediators: IL-1, IL-6, PGI2, PAF, chemokines
sequence of leukocyte extravasation
- leukocyte margination
- leukocyte rolling
- leukocyte adhesion
- emigration or transmigration
- chemotaxis
_____ mediate the processes involved in the movement of leukocytes from the blood stream into the extravascular tissue
cell adhesion molecules (CAMs)
in rolling, _____ mediate a weak, transient sticking that slows the cells forward progression
selectins (adhesion molecules)
adhesion is mediated by _____
integrins (ICAM and VCAM on endothelial cells)
emigration/transmigration of ECs through the vessel wall (diapedesis) mediated by _____; occurs mainly in the ____ of the systemic vasculature
PECAM-1; venules
chemotactic factors involved in chemotaxis
PAF (potent)
LTB4- leukotriene B4 (potent)
C5a, chemokines, bacterial lipids and peptides, fibrin degradation products (FDP)
factors that activate leukocytes during an inflammatory reaction
bacterial products, cellular debris, Ab-Ag complexes, cytokines and chemokines, chemotactic factors
activation of leukocytes characterized by production of ____ and ____ from _____; degranulation and release of _____; production of ____; synthesis and secretion of ____; altered expression of _____
leukotrienes and prostaglandins from arachidonic acid lysosomal enzymes ROS cytokines cell adhesion molecules
4 steps of phagocytosis
- attachment
- engulfment
- lysosomal degranulation
- oxidative burst
attachment mediated by ____ on targets and specific _____; engulfment into a _____; lysosomal degranulation by fusion with the ____; oxidative burst releasing ____
opsonins (IgG, C3b, collectins); specific leukocyte receptors (Fc receptor for IgG, complement receptors)
phagocytic vacuole
phagosome
ROS (superoxide, hydrogen peroxide, hypochlorous radical)
other mechanisms of intracellular killing by leukocytes
lysozyme, major basic protein, defensins, bactericidal permeability-increasing protein
cells of acute inflammation
neutrophils (morphologic hallmark of acute inflammation)
monocytes (macrophages/histiocytes)
activated macrophages have several functions including ____ and ____ cellular debris and organisms; they also take up and metabolize ____ and present _____ to immunocompetent T cells
phagocytize; digest
antigens; membrane-bound Ag
activated macrophages elaborate various factors including:
enzymes (proteases); complement and coagulation factors; cytokines (IL-1, TNF), ROS and NO, prostaglandins, growth factors
other inflammatory cell types
- lymphocytes, plasma cells (immune functions)
- eosinophils (allergic rxns, parasitic infections)
- mast cells- surface IgE- release histamine
while prostaglandins generally cause vasodilation, ____ causes vasoconstriction; another example of opposing effects: _____ promotes platelet aggregation and ____ inhibits platelet aggregation
thromboxane A2; thromboxane A2 ; prostacyclin
cells of chronic inflammation
lymphocytes
macrophages
plasma cells
eosinophils
role of growth factors and cytokines in wound healing
epithelial proliferation monocyte chemotaxis fibroblast proliferation angiogenesis collagen synthesis
3 types of exudate
- fibrinous- high protein (fibrin), few cells, cloudy
- purulent (pus)- contains cells (neutrophils); opaque
- sanguineous- pink/red fluid due to blood
neutrophils infiltrate tissue in response to _____ and _____ infections
tissue necrosis; bacterial (some fungal) infections
in acute inflammation, neutrophils begin to accumulate within ____ hours; neutrophils are replaced with monocytes/macrophages within ____ hours
4-6; 48
diffuse, permeative infiltration of neutrophils with edema
cellulitis
localized area of neutrophils or liquefactive necrosis (pus)
abscess
erosion of an epithelial surface exposing underlying connective tissue
ulcer
causes for chronic inflammation include:
- persistent infections
- prolonged exposure to a toxic agent
- immune-mediated inflammatory disease
non-specific chronic inflammation often assoc with _____
tissue repair (granulation tissue/fibrosis)
granulomatous inflammation linked to the _____
delayed type IV hypersensitivity immune reaction
morphology of granulomatous inflammation includes:
- epithelioid (activated) histiocytes
- central caseous necrosis
- multinucleated giant cells (langhans)
- collar of mononuclear cells
- heal by fibrosis
diseases characterized by granulomatous inflammation include:
- bacterial infection- M. tuberculosis
- parasitic infection
- fungal infection
- inorganic matter
- unknown etiology
PGs and LTs are derived from arachidonic acid through the action of ____ or ____
cyclo-ocygenase (PGs) ; lipo-oxygenase (leukotrienes)
aspirin and non-steroidal anti-inflam drugs reduce inflammation by ______; steroids inhibit release of ____ from _____
blocking cyclo-oxygenase activity; arachidonic acid; cell membrane phospholipids
factors that affect wound healing
- infection
- nutrition
- steroids
- mechanical factors
- poor tissue perfusion
- DM, atherosclerosis
increased vascular permeability- immediate transient- EC contraction mediated by:
histamine, BK, PAF, leukotrienes
in direct EC injury, increased vascular perm med by _____ or _____
injurious agents; ROS/enzymes from PMNs
EC retraction mediated by:
IL-1, TNF, IFN gamma
pain mediated by:
BK and PGE2