What is inflammation ?
- it is a non specific, localised and complex biological response of tissues to harmful stimuli such as pathogens, damaged cells and irritants
- the biological response involves blood vessels, immune cells an molecular mediators
What is the role of inflammation ?
- eliminates the initial cause of injury
- removes necrotic cells and tissues
- initiates and regulates repair and recovery
- it is a protective mechanism
What is an infection ?
infection describes the interaction between the invading pathogen and the inflammatory response
What are the 5 cardinal signs of inflammation ?
- Pain (dolor)
- Redness (rubor)
- Loss of function (functio laesa)
- Swelling (tumor)
- Heat (calor)
What causes redness and heat ?
- increased blood flow to the site of injury
- blood is brought from the centre of the body to the surface
What causes swelling ?
- accumulation of fluid at the site of injury
- leakage of fluid from the blood vessels to the tissues
What causes pain ?
the release of chemical mediators e.g. histamine or bradykinin
What causes the acute inflammatory response ?
1) it is initiated by mast cells, macrophages and dendritic cells
2) these will interact with pattern recognition molecules e.g. PAMPs and DAMPs
3) this results in the release of inflammatory mediators e.g. histamine and bradykinin
4) this causes the distinct vascular and cellular components
Describe the distinct vascular components
- vasodilation of blood vessels will increase blood flow and lead to redness and heat
- vascular permeability will lead to swelling
- blood stasis causes the loss of fluid from vessels allowing the accumulation of leukocytes
Describe the acute inflammatory response
1) the cut will create an opening in the skin allowing pathogens to enter the skin and cause infection
2) mast cells and macrophages will release histamine etc
3) these chemical mediators will stimulate endothelial cells of blood vessels
4) this causes vasodilation of blood vessels
5) this allows the movement of phagocytic cells into the tissue to remove pathogens
6) the wound will begin to heal and the infection is under control - homeostasis is restored
7) phagocytes will undergo apoptosis
Describe the process of extravasation
1) neutrophils are normally in an axial stream but blood stasis will force leukocytes to the vessel walls and this is known as margination
2) leukocytes will roll along the vessel wall
3) there will be adhesion of leukocytes to the endothelium
4) transmigration will occur
5) once the leukocytes are in the tissue they will carry out chemotaxis
Describe leukocyte adhesion deficiency
- there are 3 types : LAD 1, 2 and 3
- it is very rare
- the hallmarks are delayed umbilical cord sloughing and recurrent bacterial infections
- it is underpinned by defects in neutrophil adhesion
- it is an autosomal recessive mutation in the ITGB2 gene
- neutrophils are trapped in the blood vessels and they cannot reach the site of infection
How is the surrounding tissue protected in the resolution of inflammation ?
- it eradicates the threat and restoration of tissue homeostasis
- the inflammatory response is actively terminated
- anti inflammatory cytokines and chemokines are produced to terminate the inflammatory process
- apoptosis of inflammatory cells
What is chronic inflammation ?
This happens when things go wrong and it is quite destructive to the body
Describe differences between acute and chronic inflammation
- rapid onset v slow onset
- short duration v long duration
- predominantly neutrophil driven v monocyte and lymphocyte driven
- involves apoptosis v necrosis, fibrosis and angiogenesis
What causes chronic inflammation ?
- persistent injury
- prolonged toxic agent disposure
- autoimmune disease states
Give examples of pathologies in which inflammation plays a role
- diabetes
- cancer
- autoimmune diseases
- pulmonary diseases
