Inflammation
Is provoked in response to tissue injury
with microbes chemical agents cold, heat trauma
Infection
serves to destroy, dilute or wall off the injurious agent induces repair
can be potentially harmful
Introduction:
“Inflame” – to set fire.
Inflammation is “ response of vascularised tissue to injury.”
Nomenclature
Inflammation is usually indicated by adding the “-itis”
Dermatitis
Appendicitis
Tonsillitis Meningitis
Congested red mucosa
Infection forming pus
Inflammation
Acute
Chronic
Acute versus chronic inflammation are distinguished by the duration and the type of inflammatory cells
Types of inflammation
Acute inflammation short duration (hours to days) characterized by the presence of NEUTROPHILS Chronic inflammation is of longer duration (days to years) and is characterized by chronic inflammatory cells
Cells involved in inflammation
ACUTE INFLAMMATION
Neutrophils Macrophages Eosinophils occasionally
CHRONIC INFLAMMATION
Lymphocytes Plasma cells Macrophages
5 Cardinal signs of (acute) inflammation
Rubor Tumor Calor Dolor
= redness = swelling = heat = pain
Functio laesa = loss of function
The 5 Cardinal Signs of
ACUTE INFLAMMATION
Acute inflammation has two major components: 1.Vascular component 2.Cellular (leukocytes) component
ACUTE INFLAMMATION
Major events
1. Alterations in the vascular caliber & flow
2. Increased vascular permeability
3. Emigration of the leucocytes to the site of injury
Vascular events
Brief arteriolar vasoconstriction followed by vasodilation Occurs due to release in the histamine, prostaglandins & Nitrous Oxide from damaged cells
Increased intravascular pressure causes outpouring of protein-poor filtrate of plasma into interstitium-known as TRANSUDATE
Vasodilatation
Increased Vascular Permeability
It is the hall mark of acute Inflammation
1.Gaps due to endothelial cell contraction
The most common cause of increased vascular permeability Elicited by histamine, bradykinin, leukotrienes etc
•Rapid and short-lived reaction (minutes), hence immediate transient response
Direct endothelial Injury
Damage to vessels due to burns, infections, etc. - results in immediate increase in permeability and lasts until vessels are repaired, hence “ Immediate sustained response”
Leukocyte induced endothelial damage
Endothelial damage resulting from the action of activated leukocytes Delayed sustained response
Leukocyte cellular events
Leukocytes leave the blood vessels to arrive to the site of injury, through the following sequence of events:
Margination
and rolling Adhesion and transmigration Chemotaxis
Rolling
Activated endothelial cells and leucocytes express adhesion molecules - Selectins
Injurious agent
Cells normally roll past resting endothelial cells Rolling
Rolling is mediated by SELECTINS
Activation & adhesion
Expression of endothelial adhesion molecules Injurious agent
Rolling
Neutrophil Selectin is shed is activated INTEGRIN has low affinity for ICAM
high affinity format
Transmigration and diapedesis
Firm adhesion causes the leukocyte to flatten and migrate between the endothelial cells
Injurious agent
~10 Minutes
Transmigration(Diapedesis)
PECAM expressed at intercellular junctions of endothelial cells
Metalloproteases digest the basement membrane
Margination and Rolling
With increased vascular permeability, fluid leaves the vessel causing leukocytes to settleout of the central flow column and “marginate” along the endothelial surface Endothelial cells and leukocytes have complementary surface adhesion molecules which briefly stick and release causing the leukocyte to roll along the endothelium -Rolling
Margination and Rolling
Rolling is mediated by adhesion molecules known as selectins:
E-selectin (endothelium) P-selectin (platelets, endothelium) L-selectin (leukocytes) The selectins bind to complementary molecules
Adhesion
Rolling comes to a stop and adhesion results
Other sets of adhesion molecules participate:
Endothelial adhesion molecules : ICAM-1, VCAM-1 Leukocyte: Integrins
Adhesion is mediated by adhesion molecules on endothelial cells (ICAM-1, VCAM-1) that interact with integrins on the leucocytes,which are complementary to each other These adhesion molecules are ordinarily down-regulated or in an inactive conformation, but inflammation alters these to high affinity format
Transmigration (diapedesis)
Movement of leucocytes out of the vessel Occurs after firm adhesion Adhesion molecules such as PECAM help in migration of leukocytes across the vessel wall Must then cross basement membrane
Collagenases Integrins
Adhesion molecules are involved in leukocyte migration
Selectins E-selectin (endothelium) P-selectin (endothelium & platelets) L-selectin (leukocytes) Immunoglobulin family ICAM-1 (intercellular adhesion molecule 1) VCAM-1 (vascular adhesion molecule 1) Are expressed on activated endothelium Ligands are integrins on leukocytes
Integrins (a + b chain)
Expressed on leukocytes
b1 integrin binds to VCAM-1
b2 integrin binds to ICAM
Neutrophil Margination
The fluid accumulation in inflammation which is rich in proteins and inflammatory cells is
EXUDATE
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