Vasodilatation induced by Chemical mediators: Histamine &

Nitric oxide

Initially starts in the Arterioles later in the Capillaries.

Followed by Increased vascular permeability.

Stasis of blood, Loss of Plasma, Proteins and later the

WBCs.

Immediate Transient Response: 30 min. Mediated by

Histamine & leukotrienes.

Delayed response: 2 Hrs. Mediated by Kinins, complements.

Prolonged response: Mediated by direct endothelial Injury.

Regulated by the binding of complimentary Adhesion

molecules on WBC & Endothelial surface.

Surface expression is modified by Chemical mediators like

cytokines which causes Chemoattraction.

There are Four classes of Cell Adhesion Molecules

i. Selectins:: L, E, P types

ii. Immunoglobulin family:: ICAM, VCAM

iii. Integrins:: Beta-1 & Beta- 2 types.

iv. Mucin like Glycoproteins:: CD 44

1. Rolling of WBCs in Lumen

2. Adhesion to Endothelium

3. Arrest of motion

4. Activation

5. WBC migration

6. Leukocyte Homing.

Is Migration of WBCs in tissue towards the site of Injury

LOCOMOTION oriented along the CHEMICAL GRADIENT.

Chemoattractants can be Exogenous or Endogenous.

Bacterial products, Complements, leukotriens, Cytokines

are Chemoattractants.

Chemotaxis is the directional and purposeful

movement of cells by amoeboid movement

toward an area of injury in response to a

chemical mediator.

WBCs move by extending the filopodia.

Rapid assembly of Actin monomers into Actin polymers

occurs

Actin regulating proteins are ::

-Filamin

-Gelsolin

-Profilin

-Calmodulin.

Activated by Microbes, Necrotic cells, Ag-Ab complexes,

Chemotactic factors, Cytokines.

Activation leads to::

-Production of Arachidonic acid metabolites

-Secretion of Lysosomal enzymes

-Degranulation

-Secretion of cytokines

-Modulation of CAM

Movement of neutrophils toward the endothelial lining

Causes of margination

electrical charge on the endothelial cells changes

blood viscosity increases

chemical mediators

Diapedesis means “cell-walking”

When activated, neutrophils squeeze through the

endothelial gaps into the tissues by a process known as

Diapedesis

1. Recognition & Attachment of the particles to be

ingested by the leukocytes.

2. Engulfment, with subsequent formation of a phagocytic

vacuole.

3. Killing & Degradation

Mannose Receptors & Scavenger Receptors

Best attachment if the Microbe is Opsonised

by the Immunoglobulin (Ig G) or by

Complements C3b.

Extensions of the cytoplasm –pseudopods –flow around the

particle to be engulfed

Formation of phagosome: Created by plasma membrane of cell

Phagolysosome formation: fusion of phagosome membrane

with Lysosomal membrane.

Release of lysosomal granules.

Oxygen dependent Killing mechanisms

Burst in O2 consumption, Reactive O2 species.

Increased production of Hydrogen peroxide, Hydroxyl

ions, Superoxide ions, Halide ions.

“H2O2 + MPO + Halide” is the most efficient Bactericidal

mechanism in us.

H2O2: is broken down by catalase into H2O and O¨2

NADPH gets oxidizes into NADP by NADPH oxidases and

releases Superoxide anion (O¨2 ) which further converts

H2O2 into highly reactive hydroxyl radical (OH¨)

MPO: present in Neutrophils: converts H2O2 into HOCl in

presence of halides Cl.

Reactive O2 radicals:

O2 independent Mechanism of killing:

Lysozymes

Lactoferrin

Major Basic protein

Defensins

Elastase

Substance released during phagocytosis:

1. Lysosomal enzymes

2. Reactive oxygen intermediates

3. Products of arachidonic acid metabolites (prostaglandins and

leukotrienes)

These products causes endothelial damage and tissue damage.

So---Persistent/ unchecked leukocyte infiltrate itself can become an

offender.

Leads to Increased susceptibility to Infections

Defects have been identified in all levels of WBC function

Defects can be genetically inherited or Acquired.

Defects in WBC Adhesion, Phagolysosome function,

microbicidal activity

Defects in phagolysosome formation

Neutropenia, defective degranulation, delayed microbial

killing

Neutrophils –with giant granules

Increased susceptibility to infections, Albinism (due to

defect in melanocytes), nerve defects.

Also platelet dysfunction—leading to bleeding disorders.

Due to defect in microbicidal activity

Inherited defects in the genes encoding the NADPH oxidase—

which generates Superoxide.

Patients are susceptible for recurrent bacterial infections.

Acute

Inflammation

Resolution/Healing

& Repair

Chronic

Inflammation

Abscess

SinusFistula

Ulcer

Injury

Definition: Dynamic, vascularized, injury

Calor, Rubor, Dolor, Tumor, Loss of function

Vasodilatation, exudation, chemotaxis, phagocytosis.

Chemical mediators – Prostaglandins, Kinins, etc

Types Acute/Chronic, Suppurative, serous, fibrinous.

Acute / Chronic differences.

Acute & Chronic inflammation.

Suppurative

Fibrinous

Serous

Granulomatous

Eosinophilic

Exudative Inflammation:

Suppuration – Purulent - Bacterial

Fibrinous – pneumonia – fibrosis

Serous – excess clear fluid – lung

Haemorrhagic – >Damage - anthrax.

Chronic inflammation: with healing.

Granulomatous – clusters of epitheloid* cells eg. TB, Fungus,

Foreign body.