Acute Inflammation (3) Flashcards
3 major components of acute inflammation
- Dilation of blood vessels
- Increased permeability in vasculature
- Emigration of leukocytes from vascular into injury site
Exudate
Fluid with HIGH concentration of proteins and cells
Exudate implies?
Increased vascular permeability seen with an inflammatory response!
Transudate
Fluid with LOW concentration of proteins and cells
Transudate implies?
NO increase in vascular permeability
Edema
Excess fluid in interstitial tissue; can be exudate or transudate
Pus
Purulent Exudate
What is pus rich in?
Neutrophils, cell debris, microbes
How does the lymphatic system help during acute inflammation?
Increases lymph flow to drain edema fluid that accumulates due to increased vascular permeability
As the lymphatic system helps during acute inflammation, the lymph vessels and nodes may also become inflamed. What can be seen?
Red streaks
3 phases of leukocyte recruitment in the acute inflammatory response
- Margination, rolling, adhesion
- Diapedesis
- Chemotaxis
Diapedesis
Migration through the endothelium
Chemotaxis
Leukocytes more toward offending agent
Macrophages release _____ during leukocyte recruitment
IL-1 and TNF
Job of IL-1 and TNF during leukocyte recruitment?
Increase expression of P and E selectins
(Adhesion molecules)
P and E selectins job during Leukocyte recruitment?
Rolling of the leukocyte - bind, detach, bind, detach = slows them down!
Macrophages release _____ that increase the affinity of the integrins on leukocytes during recruitment
Chemokines
What receptor do integrins bind?
ICAM-1
During leukocyte recruitment, P and E selectins increase adhesion molecules, chemokines increase affinity of leukocyte integrins. What does this cause?
Leukocyte ADHESION
Once the leukocyte is adhered to the endothelium, what occurs next?
Diapedesis
What molecule controls Diapedesis?
PECAM-1 (CD31)
After Diapedesis, what occurs next?
Chemotaxis
What are chemoattractants that stimulate chemotaxis?
IL-8, Complement C5a and AA metabolites
Describe Chemotaxis
IL-8, C5a and AA metabolites bind GPCR on leukocyte surface
- Causes Actin polymerization at leading end
- Causes Myelin localization at back
- Leading edge extends filopodia that pull the leukocyte forward towards microbes
Main Leukocytes during the Acute inflammatory response?
Neutrophils
Monocytes
Lifespan of Neutrophils during Acute inflammatory response?
6-24 hours; soon replaced by Monocytes
Monocytes survive longer and become dominant cell in acute inflammatory responses. What did they replace?
Neutrophils
What are the Main Phagocytes during the Acute inflammatory response?
Neutrophils
Macrophages
Mechanisms of action of Neutrophils while acting as phagocytes during phagocytosis?
ROS, Degranulation and NET formation
Mechanisms of action of Macrophages while acting as phagocytes during phagocytosis?
NO, Cytokine release
What are the 3 steps to Phagocytosis?
- Recognition and attachment of particle to be ingested by leukocyte = Leukocyte activation
- Engulfment with formation of Phagocytic Vacuole
- Killing of microbe and degradation of ingested material
During Phagocytosis, what are the cell surface receptors that recognize microbes?
GPCR
TLR
Cytokine receptor
Phagocyte Receptor **
Types of Phagocyte Receptors?
Macrophage Mannose Receptor
Scavenger Receptor
Opsonin Receptor
What does the Macrophage Mannose Receptor bind?
Mannose and Fucose residues on glycoproteins expressed on microbes surface
Describe the Engulfment process during phagocytosis
- Binding of microbe to phagocyte receptor
- Phagocyte membrane zips up around microbe
– Creates a Phagosome - Phagosome fuses with Lysosome
= Killing of Microbe
What are the 3 things that do most of the killing and digestion of the microbe during phagocytosis?
ROS
NO
Lysosomal enzymes
Where are ROS, NO and lysosomal enzymes contained during phagocytosis?
Lysosome
What are ROS, NO and lysosomal enzymes tagged with in order to get from the ER to the lysosome?
M6P
Th___ also contributes to acute inflammation
Th17
Job of Th17 during acute inflammation?
Recruit more leukocytes
Without Th17 during acute inflammation, what results?
COLD abscesses
How is the acute inflammatory response terminated?
Inflammation decreases after removal of mediators and offending agents
Inflammation itself can produce “stop signals” to terminate the acute inflammatory response. What are those?
IL-10 and TGF-beta
Neutrophil nuclei are ____ when NETs are formed
Lost
Formation of NETs is dependent on?
Platelet activation
