Unit II: Inflammation key points/overview Flashcards
3 initiators of inflammation
- tissue damage
- bacteria
- activation of local mast cells or tissue macrophages
What can initiate histamine release from mast cells?
Direct injury, cold innervation, cross linking of IgE
Margination
Margination
- cells/proteins fall out of axial flow due to hemostasis
- Stasis due to: increased blood delivery to capillaries, but efflux remains the same
Endothelial activation occurs in…..
POST CAPILLARY VENULES==> vasodilation, increased local blood flow, increased vascular permeability
Transudate
passage of FLUID due to increased hydrostatic pressure across endothelial tight junctions
Exudate
passage of fluid, protein, and cells due to increased vascular permeability
wheal (from “wheal and flare”)
- what is it?
- pathophysio
- raised pale area around the injured skin
- caused by edema at dermal/epidermal border (causing them to seaparate)==> paleness and swelling
Flare
- what is it
- what causes it/pathophysio (x2–injury vs ice)
- bothcy red area around the “wheal”
- ice: local release of histamine from mast cells that covers area greater than ice contact
- axonal reflex= peripheral nerve stimulation opens up arterioles around the injured area
increased vascular permeability:
- Immediate transient
- augment immediate transient response
- delayed prolonged
- immediate sustained leakage
- histamine- acts within minutes but reversed within an hour
- cell derived plasma proteins augment histamine response
- inflammatory cell mediators
- physical disruption of vessel wall
Cellular phase=
Order of cells after injury
Cellular phase= passage of cells from vasculature to extracellular phase, and activation of local cells.
- Immediately: platelets (activated when exposed to ECM)
- 24hrs: Neutrophils- venous stasis and mediators help them into tissue
- 24-48 hrs: monocytes==> macrophages; tissue macrophages
- 72 hrs: Lymphocytes
diapedesis
movement of cells through the vascular wall
Neutrophil extravasation
- margination- fall out of axial flow
- weak adhesion (selectins)
- strong adhesion= ICAM and LFA-1
- e-selectin and ICAM (on endothelium) enhanced by inflammatory mediators
- LFA-1 (integrin) on neutrophils expressed when activated by local inflammatory mediators
- diapedesis toward chemotactic signal
Weibel-Palade bodies
make p-selectin and von willebrand factor
After 24 hours, inflammation is mediated by…..
tissue macrophages and monocytes- they dictate continuation or resolution (healing and regeneration) of immune response
two cells important for resolution of immune response
Macrophages and neutrophils= phagocytosis of harmful debris
2 mechanisms neutrophils kill with
- enzyme release from membrane bound granules into phagolysosomes
- ROS in azurophilic granules
Most effective method of killing in macrophages
making hyperchlorus acid from myeloperoxidase and chloride
chronic granulomatous disease- what is it, diagnosis?
inability to make ROS, nitroblue tetrazolium or neutrophil oxidative burst assay
Chronic inflammation is always accompanied by _____. Why?
FIBROSIS
chronically activated macrophages==> more activation of macrophages==> chronic stimulation of fibroblasts
- Selectins bind to ______, 3 examples.
- integrins bind to____. 2 examples
- Selectins bind to carbs–P (platelet and endothelium), E (endothelial), L (leukocyte)
-
integrins bind to immunoglobin like molecules (Ig family)
- LFA-1 (PMN) to ICAM (endothelial cell)
- VLA-4 (monocyte) to VCAM (endothelial cell)
6 Benefits of inflammation
- dilution of harmful influence
- localization of injury
- destruction of bacteria/etc
- delivery of plasma protiens and cirulating cells
- clearing of debris
- intiation of healing
- Seconds to minutes=
- Amplification of above mediators=
- histamine, serotonin
- serum proteins= hageman factor (XII), complement, coagulation facotrs, kinins
Minutes to hours after inflammation begins-
- process, mediators and morphology
- process, mediators and morphology
- Process: reflex vasoconstriction followed by vasodilation
- Mediators: Axonal reflex, histamin PGs
- Morphology: Vascular congestion, vasodilation
- Process: increased vascular permeability
- Mediators: Histamin, C3a, C5a, kinins Pgs
- Morphology: edema
Hours to Days from inflammation
Process: activation and migration of cells
- Mediators: leukotrienes, prostaglandins, cytokines
- Morphology: emigration of neutrophils, monocytes, lymphocytes
Days- process, mediators, morphology
- Process: phagocytosis and cytokine production
- mediators: PGs, cytokines,
- Morphology: Cell adaptation, necrosis, infiltrate
Days to weeks
Process, mediators, morphology
- Process: clearing of debris, cell proliferation- regeneration, scarring, immune response)
- Mediators: cytokines, growth factors
- Morphology: Angiogenesis, fibroblast proliferation, collagen synthesis, epithelial proliferation
fluid movement through cells
via increased pinocytosis
Immediate transient permeability changes (15-30 mins)
- where do they occur
- mediators
- blocked by?
Formation of endothelial gaps in venules
- post-capillary venules
- histamine, bradykinin, leukotrienes, substance P
- antihistamies
delayed prolonged leakage (hours to days)
2 causes- mediators?
cytoskeletal reorganization
- mediators: PGs, cytokines
- leukocyte–mediated endothelial injury
Immediate sustained permeability changes
Cause?
DIRECT damage to endothelial cells–affects all levels of vasculature
Factors that slow the inflammatory process
acute phase proteins, TGF-B
4 causes of chronic inflammation
- persistent injury
- persistent infection
- inability to neutralize toxin
- persistence of immune response
E-selectin is stimulated by ___(1)____. Time course (2)?
- IL-1
- peaks at 4 hrs, reversed by 24 hrs
inhibition of neutrophil rolling on endothelium
antibodies to L-lectin
