1. Inflammation is the body's protective response to rid itself of harmful stimuli like infections, toxins, and tissue damage.
2. Acute inflammation is characterized by increased blood flow, vascular permeability, and recruitment of leukocytes to the site of injury over a short period of time.
3. Chronic inflammation differs in that the inflammatory response and tissue damage persist for weeks or months, as the body attempts repair.
2. Inflammation
Overview of Inflammation
Inflammation is a protective response, designed to
rid the organism of both the initial cause of cell
injury (e.g., microbes, toxins) and the
consequences of such injury (e.g., necrotic cells
and tissues)
it can sometimes be inappropriately triggered or
poorly controlled, and is thus the cause of tissue
injury in many disorders.
Inflammation is a complex reaction in tissues that
consists mainly of responses of blood vessels and
leukocytes
may be acute or chronic
is terminated when the offending agent is
3. Acute Inflammation
Acute inflammation is a rapid host response
that serves to deliver leukocytes and plasma
proteins, such as antibodies, to sites of
infection or tissue injury
Figure: major local manifestations of acute inflammation, compared to normal. (1) Vascular dilation and increased blood flow (causing erythema
and warmth); (2) extravasation and extravascular deposition of plasma fluid and proteins (edema); (3) leukocyte emigration and accumulation in
the site of injury.
Local manifestations of acute inflammation:
1. Vascular dilation and increased blood
flow (causing erythema and warmth);
2. Extravasation and extravascular
deposition of plasma fluid and proteins
(edema);
3. Leukocyte emigration and accumulation
in the site of injury
4. STIMULI FOR ACUTE
INFLAMMATION
Infections (bacterial, viral, fungal, parasitic)
and microbial toxins
Tissue necrosis from any cause, including
ischemia
Foreign bodies (splinters, dirt, sutures)
Immune reactions (also called hypersensitivity
reactions)
5. REACTIONS OF BLOOD
VESSELS IN ACUTE
INFLAMMATION
Changes in Vascular Flow and Caliber
Vasodilation &
increased blood
flow
increased
permeability of the
microvasculature
outpouring of
protein-rich fluid
into the
extravascular
tissues
stasis: vascular
congestion
(producing
localized redness)
Increased Vascular Permeability (Vascular Leakage)
6. REACTIONS OF LEUKOCYTES
IN INFLAMMATION
A critical function of inflammation is to deliver
leukocytes to the site of injury and to activate the
leukocytes to eliminate the offending agents
Most important leukocytes in inflammation are the
ones capable of phagocytosis, namely neutrophils
and macrophages
These leukocytes ingest and kill bacteria and other
microbes, and eliminate necrotic tissue and foreign
substances.
Leukocytes also produce growth factors that aid in
repair.
Downside: may also injure normal host tissues
7. Processes involving leukocytes in
inflammation
Processes involving leukocytes
1. Recruitment of Leukocytes from the blood into
extravascular tissues (Sites of Infection and Injury)
2. Recognition of microbes and necrotic tissues
3. Removal of the offending agent
8. Processes involving leukocytes in
inflammation
Recruitment of
Leukocytes
Leukocyte
activation
(Recognition of
Microbes and
Dead Tissues)
Removal of the
Offending Agents
Vascular endothelium is
activated and can bind
leukocytes
Migration of leukocytes
across the endothelium
and vessel wall
Migration of leukocytes
in the tissues toward a
chemotactic stimulus
Recognition of the
offending agents, which
deliver signals
Activate the leukocytes
to ingest and destroy
the offending agents
and amplify the
inflammatory reaction
Phagocytosis and
intracellular killing
9. The journey of leukocytes from the vessel lumen to the
interstitial tissue is called extravasation. Extravasation can
be divided into the following steps:
i. In the lumen: In normally flowing blood in venules, red
cells are confined to a central axial column, displacing the
leukocytes toward the wall of the vessel. Because blood
flow slows early in inflammation (stasis), hemodynamic
conditions change (wall shear stress decreases), and more
white cells assume a peripheral position along the
endothelial surface. This process of leukocyte redistribution
is called margination. Subsequently, individual and then
rows of leukocytes adhere transiently to the endothelium,
detach and bind again, thus rolling on the vessel wall. The
cells finally come to rest at some point where they adhere
firmly.
Extravasation
10. ii. Migration across the endothelium and vessel
wall (transmigration or diapedesis): Chemokines
act on the adherent leukocytes and stimulate the
cells to migrate through inter endothelial spaces
toward the chemical concentration gradient, that is,
toward the site of injury or infection where the
chemokines are being produced.
iii. Migration in the tissues toward a chemotactic
stimulus: After exiting the circulation, leukocytes
emigrate in tissues toward the site of injury by a
process called chemotaxis. Both exogenous and
endogenous substances can act as
chemoattractants. The most common exogenous
agents are bacterial products. Endogenous
chemoattractants include several chemical
Extravasation (contd.)
11. Fig: The multistep process of leukocyte migration through blood
vessels
12. Phagocytosis
Engulfment of microorganisms or other cells and
foreign particles by phagocytes is called
phagocytosis. Phagocytosis involves three
sequential steps:
1. Recognition and attachment: Phargocytosis of
microbes and dead cells is initiated by
recognition of the particles by receptors
expressed on the leukocyte surface. Mannose
receptors and scavenger receptors are two
important macrophage receptors that recognize,
13. 2. Engulfment: During engulfment, extensions of
the cytoplasm (pseudopods) flow around it, and
the plasma membrane pinches off to form a
vesicle (phagosome) that encloses the particle.
The phagosome then fuses with a lysosomal
granule, resulting in discharge of the granule's
contents into the phagolysosome.
3. Killing and Degradation: Microbial killing is
accomplished largely by oxygen dependent
mechanism. Microbial killing can also occur
through the action of other substances in
leukocyte granules.
Phagocytosis (contd.)
15. Chronic Inflammation
Chronic inflammation is inflammation of
prolonged duration (weeks or months) in
which inflammation, tissue injury, and
attempts at repair coexist, in varying
combinations.
Causes:
Persistent infections (certain viruses, fungi,
and parasites)
Immune-mediated inflammatory diseases
Prolonged exposure to potentially toxic
agents