What are the cellular events in inflammation
General Principles
The influx of the leukocytes ( neutrophils & Monocytes) to the site of injury
These leukocytes ingest and destroy the injurious agents ( microbes/necrotic tissue/foreign bodies), The process is known asPHAGOCYTOSIS.
Also these leukocytes secrete growth factors needed for repair.
How does leukocytes travel from vessel lumen to the site of injury??
It is a Multistep process
Mediated and controlled by ADHESION MOLECULES and CHEMOKINES. Chemokines are Chemoattractant cytokines Which play a role in leukocyte migration
The journey of leulocytes include
a. In the lumen of blood vessels
b. Migration across the endothelium
c. Migration in the tissues towards the stimulus
Describe The events involved in the journey of leukocytes in the lumen of the blood vessels?
The steps include
a. MARGINATION: As teh blood slows down due to the changes in vascular caliber and flow,The leukocytes which normally are in the center Move towards the peripheral column & Gather along the endothelial cells. This step is known as margination.
b. ROLLING: movement of leukocytes along the endothelial surface, which is due to weak alternate weak attachment and detachment to the endothelium.
The molecules and the chemical mediators involved are shown in the illustration below
c. ADHESION: firm binding of leukocytes to the endothelium is called as adhesion.
The molecules and the chemical mediators involved are shown in the illustration below
what is diapedesis
the transmigration of leukocytes across the endothelium by squeezing through the endothelial cells is called as diapedesis.
The molecules involved are shown in the illustration below
Discuss Chemotaxis
The movement of leukocytes, in the extravascular space Towards the direction of the source of chemoattractants is called as chemotaxix
The steps involved are
chemoattractants Bind to specific receptors on leukocytes
Polymerization of actin and localization of myosin in leukocytes
Leukocytes extend filopodia
Pulls the cell in the direction of extension
Leukocytes MOVES forward
Towards the direction of the source of chemoattractants
What are chemoattractants
Exogenous:The bacterial products
Endogenous : Cytokines, C3a, C5a,Leukotriene B4
Why neutrophils predominate early in acute inflammation??
This is because
They are more in number
Respond more rapidly to chemokines than others
Attach more firmly to adhesion molecules
BUT, They are short lived!! Undergo apoptosis and disappear in 24-48 hrs
Replaced by monocytes, as they survive longer and can proliferate in tissues
The exeptions for the above rules are
Pseudomonas infections : neutrophils continues to be recruited for several days
Viral infections: lymphocytes predominate
Allergic infections: eosinophils predominate
What is the therapeutic implication of understanding this whole process??
The understanding Helped in finding the therapeutic targets for controlling harmful inflammation
Eg: TNF blockers
Integrin antagonists: Approved.. And in clinical trials.
What NEXT? After recruitment of leukocytes?
To recognize the microbes/necrotic cells/foreign bodies
Activation of Leukocytes
Phagocytosis & intracellular Killing
Click here to watch the Video tutorials of INFLAMMATION Part 2: INFLAMMATION Part 2: Cellular Events- Leukocyte Recruitment.