Acute inflammation

Cellular events in acute inflammation

Cellular phases of inflammation comprises of two processes

•       Exudation of leucocytes

•       Phagocytosis

Exudation of leucocytes

1. Changes in the formed elements of blood

•       Early stage of inflammation

•       Increased rate of blood flow – vasodilatation – slowing or stasis of bloodstream

•       Central stream of cells widens and peripheral plasma zone becomes narrower – exudation

•       Margination – redistribution – neutrophils of the central column come close to the vessel wall – pavementing

2. Rolling and adhesion:

Selectins – Helps rolling of neutrophills  over endothelial cells

–       P-selectin – rolling

–       E-selectin – associated with both rolling and adhesion

–      L-selectin – responsible for homing of circulating lymphocytes to the endothelial cells in lymph nodes

Integrins

•       Activated during the process of loose and transient adhesions

•       Between endothelial cells and leucocytes

•       Stimulation receptors for integrins on the neutrophils

•       Firm adhesion between leucocyte and endothelium

Immunoglobulin gene superfamily adhesion molecule intercellular adhesion molecule-1 (ICAM-1),

•       Vascular cell adhesion molecule-1 (VCAM-1) – tighter adhesion and stabilise the interaction between leucocytes and endothelial cells

•       Platelet-endothelial cell adhesion molecule- 1 (PECAM-1) or CD31 – leucocyte migration from the endothelial surface

3. Emigration and diapedesis :

•       Sticking of neutrophils to the endothelium

•       Movement along the endothelial surface

•       Cytoplasmic pseudopods – cross the basement membrane – damage – collagenases – extravascular space – emigration

•       Neutrophils are dominant first 24 hours

•       Monocyte-macrophages  – 24-48 hours

Diapedesis – passive phenomenon

•       RBCs being forced out

•       Raised hydrostatic pressure

•       Escape through the endothelial defects

•       Diapedesis gives haemorrhagic appearance to the inflammatory exudate

4. Chemotaxis:

Chemotactic factor-mediate transmigration of leucocytes

•       Leukotriene B4 (LT-B4)

•       Components of complement system (C5a and C3a)

•       Cytokines (Interleukins, in particular IL-8)

•       Soluble bacterial products (such as formylated peptides)

•       Chemokines e.g. monocyte chemoattractant protein (MCP-1), eotaxin – eosinophils, NK cells-  virally infected cells

Phagocytosis

Engulfment of solid particulate material by the cells – phagocytes

•       Polymorphonuclear neutrophils (PMNs) – acute inflammatory response – microphages

•       Circulating monocytes and fixed tissue mononuclear phagocytes –  macrophages

Process involves 4 stages

•       Recognition and attachment

•       Engulfment

•       Degranulation

•       Killing and degradation

1.   Recognition and attachment

•       Phagocytes & microorganism – have similar charges

•       Phagocytes covered with opsonin to facilitate bond

•       IgG opsonin

•       C_3b fraction of complement system

2. Engulfment

•       After opsonisation, particle ready to be engukfed

•       Cytoplasmic pseuodopods extend out from phagocytes

•       Phagocytic vacuole

•       Plasma membrabe enclosing phagocytic vacuole breaks

•       Engulfed material lies free in cytoplasm

•       Lysosome + Phagocytic vacuole = Phagolysosome

3.  Secretion (Degranulation)

•       Enzyme stored with in preformed granule are secreted into phagosome & extracellular environment

•       Primary or azurophillic granules – fuse with lysosome

•       Secondary or specific granules are discharged

4. Killing and degradation

Microorganisms – killed by antibacterial substances – degraded by hydrolytic enzymes

•       Oxygen dependent bactericidal mechanism

•       Oxygen independent bactericidal mechanism

•       Nitric oxide

MPO-dependent killing:

•       Enzyme MPO acts on hydrogen peroxide in the presence of halides to form corresponding hypohalous acid – potent antibacterial

MPO  independent bactericidal mechanism

•       Mature macrophages lack the enzyme MPO

•       OH^—  – Bactericidal activity

Oxygen independent killing bactericidal mechanism:

•       Liberated lysosomal granules –

•       lysis within phagosomes – 

•       lysosomal hydrolases,

•       permeability increasing factors,

•       cationic proteins (defensins),

•       lipases, ptoteases, DNAases

Nitric oxide:

•       Endothelial cells and activated macrophages

•       Nitric oxide reactive free radicals – nitric oxide synthase –  potent mechanism of microbial killing

Fate of acute inflammation

Summary

•       Cellular phases of inflammation comprises of two processes -exudation of leucocytes and phagocytosis

•       Exudation of leucocytes involves-  changes in formed elements, rolling & adhesion, emmigration& diaphesis and invasion

•       Phagocytosis involves cell eating

•       Fate of acute inflammation may be healing, regeneration, suppuration or may develop into chronic inflammation

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