Accute Inflammation Flashcards
What is acute inflammation?
It’s the body’s initial response to tissue injury. It takes minutes/hours to develop and stays for a short duration, hours/days.
It’s an innate immune response, thus it is relatively non-specific as it will respond to several types of injury.
List three triggers of acute inflammation.
1) INFECTIONS
such as bacteria, viruses, parasites, fungi, toxins
2) TISSUE DAMAGE DUE TO:
- Physical Agents: such as frost bites, burns, radiation
- Chemical Agents: such as chemical burns and irritants
- Mechanical Injury and Ischaemia: trauma, tissue crash, reduced blood flow
3) FOREIGN BODIES:
such as splinters, sutures, dirt, swallowed bones, dentures
What are a few general purposes of acute inflammation (i.e. how does it benefit the body)?
- it alerts the body
- it limits the spread of infection or injury
- it protects the injured site from becoming infected
- it eliminates dead cells/tissue
- it creates conditions required for healing
What are some local signs of acute inflammation?
- REDNESS (RUBOR): increased blood flow (hyperaemia) to injured area
- SWELLING (TUMOR): fluid accumulation because of increased permeability of vessels
- HEAT (CALOR): increased blood flow and metabolic activity
- PAIN (DELOR): release of pain mediators, and increased pressure on nerve ends
- LOSS OF FUNCTION (FUNCTIO LAESA): due to excessive swelling and pain
List some systemic changes that occur in acute inflammation.
- A fever will be caused due to pyrogens [such as IL-1, TNF-α, which are both endogenous pyrogens], which are substances that induce fever.
- As well as this, neutrophil synthesis, called neutrophilia will be increased. This occurs by G-CSF (a protein, which appears as part of the inflammation response) stimulation of bone marrow. These neutrophils are needed to replenish dead neutrophils as well as releasing immature neutrophils into the blood.
- Acute phase reactants/proteins are substances involved in the inflammatory response, these include: C-reactive protein, fibrinogen, complement and serum amyloid A protein (SAP). These are produced in the liver and their production is induced by IL-6, IL-1 and TNF-α. An increase in fibrinogen (which is sticky) will cause stacking of the RBC’s (called rouleaux) resulting in a faster sedimentation rate (which is used when the blood is centrifuged to see how fast this occurs).
- If the infection is very severe it can lead to a more generalised effect on the body sepsis/septic shock.
What are the vascular events that occur in acute inflammation?
- Vasodilation will occur due to histamine and serotonin released from injured cells, as well as sentinel cells that respond to trauma such as mast cells and macrophages.
- There will also be increased blood flow to the injured area, which results in an influx of white blood cells, oxygen and nutrients to that area.
- Fibrinogen clots are formed in order to wall off the injured area.
- The blood vessel permeability also increases due to contraction of endothelial cells; this results in leakage of fluid and cells into the injured tissue.
Inflammatory exudate is fluid that gets into the tissue. The contents of this include- water, salts, small plasma proteins (e.g. fibrinogen) and inflammatory cells.
List the different types of inflammatory exudate.
- SEROUS: clear, thin, watery
- PURULENT: contains pus (pus contains dead neutrophils, microbes, etc.), opaque, thick, viscous
- FIBRINOUS: composed mainly of fibrin and fibrinogen
- HAEMORRHAGIC: bloody, as red blood cells predominate
What are some cellular events that occur in acute inflammation?
As well as there being vascular events, there are also processes the cells go through.
First, there is the migration and accumulation of cells into the area that is affected; the first cells to populate the damaged area are the neutrophils.
Their exit from the blood vessel is quite complex. The reason for this is they can help remove dead or injured cells as well as combat infection inflicted by the pathogens by phagocytosing the dead pathogens and dead tissue. They only live briefly, and dead neutrophils form the pus.
There is then migration and accumulation of monocytes at the injured site, which differentiate into macrophages. Macrophages are very good at phagocytosis and help clear up the injured site. They also release factors that promote tissue repair (TGF- β)
What are the five steps of neutrophil recruitment?
Acute inflammation involves neutrophil recruitment, which is very important. It is a multistep process involving the neutrophils having to adhere to the luminal surface of the endothelium and then migrate through the vessel wall.
1) Margination and rolling
2) Integrin activity by chemokines
3) Firm adhesion to endothelium
4) Transmigration through endothelium into tissue
5) Chemotaxis to inflamed site
Describe the neutrophil recruitment to the endothelial cells on the blood vessel wall.
When the leucocytes travel in the blood vessel, they generally travel in the middle to avoid hitting the wall. Upon inflammation, the blood vessels dilate in the inflamed area and the blood travels slower. The leucocytes, as a result, start leaving the centre and going towards the wall of the blood vessel (endothelial layer).
Next, a series of molecules will regulate the transient adhesion of the leucocyte to the endothelial cells that have been changed/activated. It is a transient process, so when the leucocyte binds the flow of the blood causes it to soon detach and re-attach and repeat as it starts rolling down the endothelium.
Then if the conditions are right and there are chemokines present, the integrins will get activated and the cell will be immobilised and stay fixed to the endothelial cell. Without this step, there can be no progression to the cell squeezing through the blood vessel wall and into the tissue.
What are the three molecules involved in neutrophil recruitment?
- SELECTINS
- INTEGRINS
- IMMUNOGLOBULIN SUPERFAMILY CELL ADHESION MOLECULES (CAMs)
Describe what selectins do, and the different types of selectins.
They mediate the rolling of neutrophils on the surface of endothelial cells. They are expressed by the activated endothelium (i.e. endothelium in an area of the blood vessel where there is acute inflammation, because in a normal blood vessel leucocytes should not adhere to the vessel wall).
There are two types: P-selectin and E-selectin.
P-selectin is present in pre-formed granules.
E-selectin is actively induced by IL-1 and TNF-α
The selectins bind to ligands on the neutrophils. These ligands are carbohydrate molecules(PSGL-1, sialyl-Lewisx).
This is a low-affinity interaction and so is disrupted by blood flow causing repetitive binding and detaching of the neutrophil which is why it rolls down the endothelium.
Describe integrin activation via chemokines.
The rolling neutrophils express integrins (LFA-1). These integrins are initially in a low-affinity configuration and so there is no binding to ligands on the endothelium.
Activated endothelial cells produce chemokines, these chemokines bind to receptors on the neutrophils. This causes integrin activation and they move up to a high-affinity configuration.
Now the integrins on the neutrophil can bind to the ligands on the endothelium; this is a firm adhesion of the neutrophils to the endothelium. The integrin ligands are called ICAM-1 and VCAM-1.
Describe neutrophil transmigration and phagocyte mobilisation (chemotaxis).
Neutrophils migrate through the interendothelial spaces, pass through the vessel wall and enter the tissue. They then migrate (chemotaxis) through the tissue towards inflamed site.
The neutrophils leave the blood vessel wall and once in the tissue, they follow the chemoattractant gradient towards the site of infection. This would’ve been detected by sentinel cells like dendritic cells and macrophages that are present and then release chemokines to alert the rest of the immune system. The chemokines act on the endothelial cells which cause them to do various things.
The chemoattract molecules [chemokines (IL-8), complement components (C5a), bacterial components (formyl-methionyl peptides) are released by the microbe/ macrophages. The neutrophils bind to these chemoattractant molecules and move closer to the site of infection.
Monocytes use a similar mechanism to leave the blood vessels and enter the sites of inflammation.
How do neutrophils destroy pathogens?
To destroy the pathogen, the neutrophils may release their granule content (which contains enzymes that are toxic to the pathogen), phagocytose the pathogen, or they may generate reactive oxygen species to destroy it.
They could also form neutrophil extracellular traps (NETs), which are very sticky that pathogens stick to and get trapped.
Examples of neutrophil granules include: Azurophil granules, specific granules, gelatinase granules, secretory granules.
