What is the difference between acute inflammation and chronic inlfmammtion?
Acute inflammation has a rapid onset, short duration and results in fluid, plasma protein and cellular exudate to site of injury. Results in neutrophilic leukocyte accumulation.
Chronic inflammation has an insidious onset, long duration, attracts lymphocytes and macrophages to site of injury and results in scarring.
Define inflammation:
A protective response intended to eliminate the cause and consequence (necrotic cells and tissue) of cell injury.
List the 5 stages of acute inflammation:
- Recognition
- Recruitment
- Removal
- Resolution
- Regulation
How are PRR used to recognise the cause and consequence of injury?
They detect the cause or consequence of injury and release chemical mediators that initiate vascular and cellular changes that lead to the recruitment of leukocytes to the site of injury.
How do PAMPS recognise the cause and consequence of injury?
- They are toll like receptors: Recognise patterns that are unique to bacteria, viruses and other pathogens.
- detect eg. Lipopolysaccharides (LPS), Lipoteichoic acid, unique surface glycans, viral RNA.
How do DAMPS recognise the cause and consequence of injury?
- They are Inflammasomes: recognise products of dead cells and some microbial products.
- detect eg. Uric acid, ATP, decreased K+ concentration
Define vascular change:
Rapid response designed to deliver leukocytes and plasma protein to the site of injury.
Provide examples of vascular change:
- vasodilation
- increased vascular permeability
- stasis
What are the mediators of vascular change?
Immediate and short term mediators:
- histamine, bradykinin, leukotrienes (chemical mediators)
- endothelial cell contraction
Slow, prolonged mediators:
- IL-1 and TNF
- Changes in cytoskeleton
What are the features of vascular change?
- increased hydrostatic pressure
- accumulation of interstitial fluid
- ultrafiltrate
- low protein concentration, few cells
List the 5 steps leading to leukocyte recruitment at site of injury:
- Margination
- Rolling
- Adhesion
- Transmigration
- Migration/chemotaxis
What is leukocyte adhesion in inflammation mediated by?
Integrins, which have a low affinity until activated by chemokines.
What is chemotaxis?
A chemical gradient produced by exogenous (infection) and endogenous (host factor) sources.
What are the cardinal signs of inflammation?
- heat : vasodilation causes increased blood flow to region
- redness: vasodilation, congestion
- swelling: vasodilation and vascular permeability leading to extravasation of fluid.
- pain: compression of tissues and direct effect of inflammatory mediators
- loss of function: direct effect of injury, or due to pain and swelling.
Define opsonization:
a process by which a pathogen is marked for ingestion and destruction by phagocytes.
Which cellular functions do leukocyte activation enhance?
- phagocytosis
- intracellular destruction of phagocytosed microbes and debris
- release of substances that destroy extracellular microbes and degrade tissue
- produce cellular mediators to amplify the inflammatory response
What does the phagolysosome do?
facilitates killing and degradation of the phagocytosed material (by the production of free radicals and the action of powerful enzymes)
What occurs when phagocytosis is initiated?
the signalling cascade that leads to cytoskeletal rearrangements and assembly of actin by the phagosome is activated.
What is the respiratory burst?
A reaction that leads to the production of reactive oxygen species (ROS) through the action of an enzyme called NADPH oxidase/phagocytic oxidase.
How do lysozyme kill?
Oligosaccharide coat degradation
How do Major basic protein kill?
Cytotoxic to parasites
How do defensins kill?
Create holes in microbe membranes
Why is activity of neutral proteases (eg. elastase, collagenase, cathepsins) checked by anti-proteases?
in order to limit damage to host tissue
What happens in resolution of inflammation?
Damage can effectively be replaced or regenerated with same cells or repaired by scar formation, so that the function of the tissue is restored.
