Inflammation

SIR RAO SHAHEER

Inflammation: Definition.

(Leukocytes,
Complement
Antibodies,
Etiological

Defense
System
Agent

etc..)
• Inflammation is defined as the local response
of living mammalian tissues to injury from
any agent.

WAR
• It is a body defense reaction.
– Eliminates injurious agent,
– Limits the spread of Injurious Agent.
– Followed by removal of the necrosed cells and
tissues.
Inert materials such as foreign bodies.
Chemical agents like organic and inorganic poisons
Physical agents like Heat, Cold, Radiation, Mechanical Trauma
Immunological agents like cell-mediated and antigen-antibody
reactions.
Infective agents : Bacteria, Viruses And Their Toxins, Fungi,
INJURIOUS AGENTS CAUSING INFLAMMATION:
Parasites.
SIGNS OF INFLAMMATION

• The Roman writer Celsus in 1st century A.D. named

the famous 4 cardinal signs of inflammation as:
I) Rubor (Redness)
II) Tumor (Swelling)
III) Calor (Heat)
IV) Dolor (Pain).
• To these, fifth sign Functio Laesa (loss of function)
was later added by Virchow.
TYPES OF INFLAMMATION

• Depending upon the defense capacity of the

host and duration of response, inflammation
can be classified as
1. ACUTE INFLAMMATION
2. CHRONIC INFLAMMATION
 Acute Vs Chronic
Feature Acute Chronic

Onset Rapid; Mins to Hrs. Slow, Takes days

Cells Neutrophils Lymphocytes,

Macrocytes/Monocytes

Tissue Injury Mild, Self Limited Severe, Progressive

Signs: Local, Systemic. Prominent Less Prominent

ACUTE INFLAMMATION
Characteristics of Acute Inflammation:

- Short Duration- < 2 weeks

- Early Body Reaction
- Resolves Quickly
- It is followed by Healing
• It can be divided into following two events:
I. Vascular events
II. Cellular events
 Events
VASCULAR CELLULAR
•Increased Blood flow to the •Recruitment of the Leukocytes
Injured Area
•To bring the Cells and Proteins to •Activation of Leucocytes- which
Site of Injury. will destruct the invaders, produce
the mediators.
•Vasodilatation and Increased
Vascular Permeability of the Blood •Phagocytosis.
Vessels near the Site.
I. VASCULAR EVENTS

• Alteration in the microvasculature (arterioles,

capillaries and venules) is the earliest response
to tissue injury.
• These alterations include:
A. Haemodynamic changes.
B. Changes in Vascular Permeability.
A. Haemodynamic Changes:
• Sequence of changes are under:
1. Transient vasoconstriction of arterioles.
• Immediate vascular response.

3-5 SECONDS FOR MILD INJURY

5 MINS FOR SEVERE INJURY

2. Persistent Progressive Vasodilatation:
• Mainly Arterioles, less extent Venules and
Capillaries.
• Occurs after 30 mins/ Half an Hour of Injury.
• Causes increased blood volume in the injured area
• Responsible for the signs: RUBOR AND CALOR
3. Progressive Vasodilatation- Increased Local
Hydrostatic Pressure:
• Results in transudation of fluid into Extracellular
Space.
• This leads to local swelling- TUMOR
4. Stasis of Microcirculation:
• Increased concentration of RED CELLS
• Leading to Increased Viscosity of the Blood at
the site of Inflammation.
5. Leucocytic Margination:
• Peripheral orientation of leucocytes (mainly
neutrophils) along the vascular endothelium.
• The leucocytes stick to the vascular
endothelium briefly, and then move and
migrate through the gaps between the
endothelial cells into the extravascular space.
• This process is known as emigration.
2. Altered Vascular Permeability

• Increased vascular permeability in acute

inflammation by which normally non-permeable
endothelial layer of microvasculature becomes leaky
can have following patterns and mechanisms.
MECHANISMS OF INCREASED VASCULAR PERMEABILITY:

i) Contraction of Endothelial cells.

ii) Mild Endothelial Damage.
iii) Leucocyte-mediated endothelial injury.
iv) Leakiness in neovascularisation/Transcytosis
1) Contraction of Endothelial cells.
• Most common mechanism.
• Affects Venules exclusively while capillaries
and arterioles remain unaffected.
• Temporary in nature.
• Mediated by the histamine, bradykinin and
other chemical mediators.
• Reversible.
• Short duration (15-30 minutes).
• Eg: Thermal injury of skin
Normal Venule
Leaky Venule
2. Mild Endothelial Damage.

• Affects Venules and Capillaries.

• Seen in Burns/Sun Burns/UV radiation.
• Mediated by cytokines such as Interleukin-1 (IL-1)
and tumour necrosis factor (TNF)-a.
• Seen after 4-6 hours following injury and lasts for
several hours to days.
Damaged Venule
iii) Leucocyte-mediated endothelial injury.

• Adherence of leucocytes to the endothelium at

the site of inflammation may result in
activation of leucocytes.
• The activated leucocytes release proteolytic
enzymes and toxic oxygen species which may
cause endothelial injury and increased
vascular leakiness.
• This form of increased vascular leakiness
affects mostly venules and is a late response.
Damaged Venule
iv) Leakiness in Neovascularisation/Transcytosis.

• Increased transport of Fluids and Proteins

across the intracellular channels
(Transcytosis).
• The newly formed capillaries under the
influence of Vascular Endothelial Growth
Factor (VEGF) during the process of repair
and in tumours are excessively leaky.
Transcytosis.
 II. CELLULAR EVENTS
• The cellular phase of inflammation consists of
2 processes:
1. Exudation of Leucocytes. (Influx to the site
of Injury)
2. Phagocytosis. (Ingestion and Destruction of
injurious Agents)
1. Exudation of Leucocytes.
• The escape of leucocytes from the lumen of
microvasculature to the interstitial tissue is the
most important feature of inflammatory
response.
• In acute inflammation, polymorphonuclear
neutrophils (PMNs) comprise the first line of
body defense, followed later by monocytes
and macrophages.
CHANGES LEADING TO MIGRATION OF
LEUCOCYTES:

I. Margination and Pavementing of Blood

Elements.
II. Rolling and Adhesion.
[Link].
IV. Chemotaxis.
Margination and
Pavementing of
Blood Elements. Rolling and Adhesion Emigration.
I. Margination and Pavementing of Blood Elements.
VASODILATATION

INCREASED RATE OF FLOW OF BLOOD

STASIS

CHANGES IN THE NORMAL AXIAL FLOW OF BLOOD

i.e. central stream of cells widens and peripheral plasma zone
becomes narrower because of loss of plasma by exudation. This
phenomenon is known as MARGINATION.

REDISTRIBUTION OF NEUTROPHILS OF THE CENTRAL

COLUMN TO THE VESSEL WALL : PAVEMENTING.
NORMAL AXIAL FLOW OF BLOOD
MARGINATION. PAVEMENTING.
II. Rolling and Adhesion

• Peripherally marginated and pavemented

neutrophils slowly roll over the endothelial
cells lining the vessel wall (rolling phase).
SELECTINS ROLLING
SELECTINS ROLLING
SELECTINS ROLLING
SELECTINS ROLLING
 CELL ADHESION MOLECULES (CAMS) EXPRESSED ON
ENDOTHELIAL CELLS GETS ACTIVATED BY TNF & IL-1 AND
BRING ABOUT ROLLING OF LEUCKOCYTES (WEAK BONDING)

SELECTINS
(3 types of Selectins)

P- SELECTIN (CD62)- INVOLVED IN ROLLING

E-SELECTIN (E-CAM)- INVOLVED IN BOTH ROLLING

AND ADHESION

L-SELECTIN (L-CAM)- ON THE SURFACE OF

LYMPHOCYTES AND NEUTROPHILS (HELPS IN
HOMING OF LEUKOCYTES TO LYMPH NODES)
This is followed by transient bond between the
leucocytes and endothelial cells becoming firmer-
ADHESION PHASE.

Integrin Ligand

Integrins
ADHESION
Integrins proteins gets activated (by IL-1, TNF)
during the process of loose and transient
adhesions between endothelial cells and
leucocytes.
III. Emigration.

• After sticking of neutrophils to endothelium,

they move through a suitable site between the
endothelial cells by cytoplasmic pseudopods.
• Neutrophils lodged between the endothelial
cells and basement membrane cross the
basement membrane by damaging it locally
with secreted collagenases and escape out into
the extravascular space; this is known as
EMIGRATION.
• Simultaneous to emigration of leucocytes,
escape of red cells through gaps between the
endothelial cells, diapedesis, takes place.

diapedesis
IV. Chemotaxis
• The transmigration of leucocytes after crossing
several barriers to reach the interstitial tissues is a
chemotactic factor mediated process called
chemotaxis.
• The following agents act as potent chemotactic
substances for neutrophils:
i) Leukotriene B4 (LT-B4)
ii) Components of complement system (C5a and C3a
in particular)
iii) Cytokines (Interleukins, in particular IL-8)
iv) Soluble bacterial products
2. Phagocytosis.
• Phagocytosis is defined as the process of
engulfment of solid particulate material by the
cells (cell-eating).
• The cells performing this function are called
phagocytes.
• There are 2 main types of phagocytic cells:
• i) Polymorphonuclear neutrophils (PMNs)
which appear early in acute inflammatory
response, sometimes called as microphages.
• ii) Circulating monocytes and fixed tissue
mononuclear phagocytes, commonly called as
macrophages.
Phagocytosis of the microbe by polymorphs and
macrophages involves the following 3 steps:

1. Recognition and attachment.

2. Engulfment.
3. Killing and degradation.
1. Recognition and Attachment:

• Special receptors on the phagocytes recognize

the microbes/necrotic cells.
Phagocytic Receptors:
1. Mannose Receptors
2. Scavenger Receptors
3. Opsonin Receptors- IgG Opsonins, C3b
Opsonin, Lectins.
2. Engulfment.
Microbes recognized by receptors are ready to be engulfed by
PMN/Macrophage

Cytoplasmic pseudopods of Phagocytes formed

from activated actin filaments of cell wall will engulf the microbe

Phagocytic vacuole (Phagosome) is formed in the cytoplasm from

the detached cell membrane which previously engulfed microbe by
its pseudopods.

The phagosome fuses with one or more lysosomes of the cell and
form bigger vacuole called phagolysosome.
3. Killing and degradation.
• Destruction of Phagocytosed microbes/Dead
cells by following mechanisms:
A. Intracellular mechanisms: (in Phagolysosomes)
1. Oxidative Bactericidal Mechanism
a. By Oxygen Free Radicals.
• Myeloperoxidase (MPO)-dependent
• Myeloperoxidase (MPO)-independent
b. By Lysosomal granules.
2. Non-oxidative Bactericidal Mechanism
B. Extracellular mechanisms:
THANK YOU