7 - Inflammation (early events) Flashcards
Goal of inflammatory reaction
To bring leukocytes and plasma proteins normally circulating in blood to the site of infection of tissue damage, eliminate the causative agent an initiate healing
Types of inflammation
Acute or chronic
onset of acute and chronic inflammation
- Acute: Fast (minutes or hours)
- Chronic: Slow (days, months or years)
Cells involved in acute and chronic inflammation
- Acute: Mainly neutrophils
- Chronic: Monocytes/macrophages, lymphocytes
Tissue injury, fibrosis of acute and chronic inflammation
- Acute: Mildm self limited
- Chronic: Often severe, progressive
Local and systemic signs of acute and chronic inflammation
- Acute: Prominent
- Chronic: less prominent
Cardinal signs of inflammation
- Redness (increased blood flow)
- Heat (increased blood flow)
- Swelling (leakage of cells and fluid into tissues)
- Pain (increased nerve sensitivity due to chemical mediators)
- Loss of function
Causes of inflammation
- Infective agents
- Foreign bodies (dirt, splinters, implants)
- Immune reactions (hypersensitivity & autoimmune)
- Tissue necrosis (death)
- Physical agents (trauma, heat, cold)
- Chemical agents (drugs, toxin)
Inflammatory process
- Offending agent is recognised by Macrophages, dendritic cells and mast calls which then produce chemical mediators (cytokines)
- Leukocytes (neutrophil and monocytes) are recruited from the circulation to the site where the offending agent is located
- Leukocytes and proteins are activated to destroy and eliminate the offending substance
- The reaction is controlled and terminated
- The damaged tissue is repaired
Two components of inflammatory responses
Vascular changes and cellular events
Vascular changes
Maximise movement of proteins and leukocytes from circulation to site of infection/injury.
Examples of vascular changes
Vasodilation, increased bloodflow and permeability
Vasodialtion
- Action of mediators (histamine) on vascular smooth muscle
- Initial constriction (transient)
- Arterioles dilate followed by capillary bed expansion
- Increased blood flow → redness & heat
Increased permeability
- Outpouring of protein rich fluid into extravascular tissues (exudate)
- causes swelling
Two ways permeability is changed
- Retraction of endothelial cells (gaps appear between endothelial cells)
- Endothelial injury (Direct damage)
End result of change permeability
- Fluid and proteins escape
- small molecules first, fibrinogen last
- ↑ osmotic pressure of tissue
- swelling
Cellular events
- Leukocytes that are recruited to sites of inflammation eliminate the offending agents following their activation
- Most important leukocytes in typical inflammatory reactions are the ones
capable of phagocytosis - Neutrophils and macrophages (slower responders)
Which cells produce growth factors that aid in repair
Macrophages, stay longer than other cells
Role of cytokines in leukocyte emigration
TNF and IL-1 act on the endothelium of venules near the site of infection to initiate leukocyte emigration into tissues
Role of chemokines in leukocyte emigration
Provide signals to leukocytes to help them traffic to the site of infection once they have migrated into
tissues (chemotaxis)
TNF and IL-1 actions
Endothelial activation (pain, fever, metabolic abnormalities)
Loose attachment and rolling of leukocytes
- In response to cytokines, endothelial cells upregulate expression of adhesion molecules called selectins
- selectins bind to surface carbohydrates on leukocytes
- repetitive process of leukocytes becoming tethered to the endothelium, flowing blood disrupting binding and bonds reforming downstream
Firm adhesion
- in response to chemokines, integrins expressed on leukocytes assume a highaffinity state
- endothelial cells upregulate expression of adhesion molecules ICAM-1 and
VCAM-1 that bind to integrins expressed by leukocytes - firm binding of integrins to their ligands arrests the rolling, cytoskeleton of
leukocytes is reorganised such that they spread out on the endothelial surface
Leukocyte migration
- chemokines stimulate the motility of leukocytes, as do bacterial products and products of complement activation
- leukocytes begin to migrate between endothelial cells, through the vessel wall
and along the concentration gradient of these chemoattractants
Chemotaxis
Movement of leukocytes after emigration towards an
increasing concentration of a chemotactic agent (usually a protein or polypeptide)
Chemoattractants
Both exogenous and endogenous substances can
act as chemoattractants (e.g. bacterial products, chemokines, complement components)
Leukocyte activation
- Leukocytes require activation in order to perform functions
- Neutrophils and macrophages can become activated
- Induced by a variety of chemical mediators
- Functions following activation include phagocytosis, lysis/killing of injurious particles and release of further chemical mediators
Phagocytosis
The process by which neutrophils and macrophages ingest debris / foreign particles
3 phases of phagocytosis
- Recognition and attachment by receptors on
surface of macrophages - Engulfment
- Killing and degradation
Phagocytosis engulfment
- Pseudopods form around organism
- Foreign material incorporated within cell vacuole (phagosome)
- Fusion with lysosomes and release of lysosomal contents
phagocytosis killing and degradation
Reactive oxygen species, nitric oxide, lysosomal enzymes
Resolution
Restoration of tissue to a completely normal state after acute inflammation or other tissue damage or death
When is resolution most likely to occur
- when cell death and tissue damage is minimal
- when damaged cells are capable of regeneration
- when causative organism is rapidly eliminated
- where local conditions favour removal of exudate
Process of resolution
- Return to normal permeability
- Drainage of fluid & proteins into lymph
- Pinocytosis into macrophages
- Phagocytosis of apoptotic neutrophils
- Phagocytosis of necrotic debris
- Disposal of macrophages
Serous inflammation
- Characterised by presence of thin, watery fluid in exudate
- Commonly seen in blisters from burns or viral infections
Purulent inflammation
- Large amounts of pus (dead leukocytes & bacteria), neutrophils, necrotic cells, edema fluid
- Caused by pyogenic bacteria (staph spp.)
- Central region of necrotic cells with infiltration of neutrophils
Fibrinous inflammation
- Characterised by entry of fibrinogen (clotting factor) into tissues
- Fibrinogen is cleaved to form fibrin and when not
removed it can lead to scarring - Inflexible sheets of fibrin
Ulcerative inflammation
- Excavation in tissue surface produced by shedding of necrotic inflammatory tissue
- Commonly seen in mucosa of mouth, stomach and
intestines
