Chapter 3: Inflammation and repair
Inflammation: major players:
1. Mediators: Cell derived mediators can release histamine, serotonin, leukotrienes, and
prostaglandins. Plasma derived mediators are produced by the liver and result in the
complement (C5a, C3a) or factor XII.
2. Receptors: like TLR or lectin (extracellular) or NLPR-3 (intracellular).
3. Vessel wall: the endothelium wall. Locally increased blood flow, dilatation of vessels,
increased permeability, and accumulation of exudate (protein rich fluid with mostly white
and red blood cells).
4. Migration of leukocytes through vessel wall: P and E-selectin causing the leukocyte to roll
along the vessel wall. Via integrin the leukocyte stops rolling and adheres. Upon histamine
the P-selectin goes to surface of endothelial cell.
Diapedesis = the migration of leukocyte from blood to tissue
Chemotaxis = the targeted migration via chemical gradient of (C5a, leukotriene B4 and some
cytokines like Il-8).
Phagocytosis and the destruction of microorganisms:
1. Recognition and attachment of microbe to receptor
2. Engulfment of microbe, phagocyte membrane zips around
3. Fuses with lysosome and becomes phagolysosome
4. Via NO and ROS in phagolysosome killing of the microbe
5. Degradation of microbe by enzymes in the phagolysosome.
NADPH oxidase = killing of microbe, happens in macrophage and neutrophil.
MPO = killing of microbe, need of chloride. Only happens in neutrophil.
Neutrophil: has specific granule and azurophilic granule. When neutrophil dies after releasing its
granules it ejects NET, nuclear protein trap around the pathogen.
Eosinophil: major function is the destruction of extracellular pathogens, mostly larger ones.
Tissue damage by leukocyte:
1. Regurgitation, lysosome fuses with phagosome before closing, result in the enzymes of the
lysosome being released
2. Frustrated phagocytosis, the surface is to big to phagocytose, and thereby releasing its
enzymes in the extracellular surface
3. Release of dead leukocytes
Body protects itself from this by circulation of a1-antitrypsin and antioxidative species against ROS.
Morphological patterns of acute inflammation:
1. Serous: a lot of exudate, relative few inflammatory. Heals very slow. Example is blister or
burn
2. Fibrinous: high protein exudate including fibrinogen to make fibrin.
3. Purulent: exudate with numerous inflammatory cells, a lot of dead cells with the
accumulation of pus, abscess
4. Ulcerous: necrotizing inflammation that leads to a surface defect, happens upon damage.
Cytokines (TNF or Il-1):
- Local inflammation, increase permeability and activation of leukocytes
- Protective effects, brain results in fever, liver results in acute phase proteins and bone
marrow in more leukocyte production.
- Pathological effects, low heart output, pro-clotting, and increased insulin resistance in the
muscle.
Inflammation: major players:
1. Mediators: Cell derived mediators can release histamine, serotonin, leukotrienes, and
prostaglandins. Plasma derived mediators are produced by the liver and result in the
complement (C5a, C3a) or factor XII.
2. Receptors: like TLR or lectin (extracellular) or NLPR-3 (intracellular).
3. Vessel wall: the endothelium wall. Locally increased blood flow, dilatation of vessels,
increased permeability, and accumulation of exudate (protein rich fluid with mostly white
and red blood cells).
4. Migration of leukocytes through vessel wall: P and E-selectin causing the leukocyte to roll
along the vessel wall. Via integrin the leukocyte stops rolling and adheres. Upon histamine
the P-selectin goes to surface of endothelial cell.
Diapedesis = the migration of leukocyte from blood to tissue
Chemotaxis = the targeted migration via chemical gradient of (C5a, leukotriene B4 and some
cytokines like Il-8).
Phagocytosis and the destruction of microorganisms:
1. Recognition and attachment of microbe to receptor
2. Engulfment of microbe, phagocyte membrane zips around
3. Fuses with lysosome and becomes phagolysosome
4. Via NO and ROS in phagolysosome killing of the microbe
5. Degradation of microbe by enzymes in the phagolysosome.
NADPH oxidase = killing of microbe, happens in macrophage and neutrophil.
MPO = killing of microbe, need of chloride. Only happens in neutrophil.
Neutrophil: has specific granule and azurophilic granule. When neutrophil dies after releasing its
granules it ejects NET, nuclear protein trap around the pathogen.
Eosinophil: major function is the destruction of extracellular pathogens, mostly larger ones.
Tissue damage by leukocyte:
1. Regurgitation, lysosome fuses with phagosome before closing, result in the enzymes of the
lysosome being released
2. Frustrated phagocytosis, the surface is to big to phagocytose, and thereby releasing its
enzymes in the extracellular surface
3. Release of dead leukocytes
Body protects itself from this by circulation of a1-antitrypsin and antioxidative species against ROS.
Morphological patterns of acute inflammation:
1. Serous: a lot of exudate, relative few inflammatory. Heals very slow. Example is blister or
burn
2. Fibrinous: high protein exudate including fibrinogen to make fibrin.
3. Purulent: exudate with numerous inflammatory cells, a lot of dead cells with the
accumulation of pus, abscess
4. Ulcerous: necrotizing inflammation that leads to a surface defect, happens upon damage.
Cytokines (TNF or Il-1):
- Local inflammation, increase permeability and activation of leukocytes
- Protective effects, brain results in fever, liver results in acute phase proteins and bone
marrow in more leukocyte production.
- Pathological effects, low heart output, pro-clotting, and increased insulin resistance in the
muscle.
