237
execution. Several of these cellular components serve as the major mediators of
both immune response and inflammation. Cytokines, a prominent inflammatory
mediator class, regulate differentiation of various cellular components of innate and
adaptive immunities.
10.1.2 Inflammation and Its Players
Inflammatory response upon pathogenic encounter is evoked when the host cells
recognize specific, conserved molecules termed as PAMPs (pathogen-associated
molecular pattern) present on the surface of the pathogen and express PRRs (pattern
recognition receptors), which belong to the Toll-like family of receptors (TLRs).
The TLRs recognize the lipopolysaccharide-like PAMP present on the surface of
microorganisms. On the other hand, injured tissue following mechanical or chemical exposure expresses damage-associated molecular patterns (DAMPs) that can be
recognized by the TLRs (El-Asrar 2012). This would initiate the release of inflammatory mediators to recruit more immune cells to the site in order to re-establish
homeostasis via remodeling or elimination of damaged cells or pathogens by complement activation and phagocytosis respectively.
Inflammatory response is broadly divided into acute and chronic on account of
its duration. Acute inflammation sets off once the irritant has been removed and the
body is adequately protected. However, chronic inflammation occurs when the
acute response fails to remove the noxious agent or if the tissue homeostasis is not
re-established, eventually leading to undesired immune reactions which may impair
tissue or organ function. Persistent inflammatory responses act as catalysts for the
development of many pathological manifestations. The link between inflammation
and the development of various pathogeneses is shown in Fig. 10.1.
Acute inflammation proceeds through vascular and cellular events. Vascular
events are the initial response to inflammatory stimuli and are induced by the
plasma-derived factors released by the injured tissue. Histamine and bradykinin are
the important mediators of vascular events. During vasodilation, volume of blood in
the area near the injury increases, resulting in redness (erythema). Vascular permeabilization facilitates influx of fluid and cells from the dilated capillaries into the site
of injury, resulting in edema. Endothelial gap formation facilitates neutrophil leakage, extravasation to the site of injury for phagocytosis, and clearance of the pathogen. Exudation of fluid activates kinin, clotting, and fibrinolytic systems which
facilitate the cellular events associated with acute inflammation. Cellular events
encompass the influx of leukocytes from the capillaries into the site of injury (leukocyte extravasation) facilitated by chemokines. They could accomplish phagocytotic clearance of the foreign component or damaged cells. However, in case of
chronic inflammatory response, either of the immune responses or both are activated in an attempt to counteract the cause of inflammation. Inflammation is initiated by the release of a vast array of mediators or effectors from injured tissues or
invading pathogens and immunologically activated cells.
10 Anti-inflammatory Molecules: Immune System Mediators
execution. Several of these cellular components serve as the major mediators of
both immune response and inflammation. Cytokines, a prominent inflammatory
mediator class, regulate differentiation of various cellular components of innate and
adaptive immunities.
10.1.2 Inflammation and Its Players
Inflammatory response upon pathogenic encounter is evoked when the host cells
recognize specific, conserved molecules termed as PAMPs (pathogen-associated
molecular pattern) present on the surface of the pathogen and express PRRs (pattern
recognition receptors), which belong to the Toll-like family of receptors (TLRs).
The TLRs recognize the lipopolysaccharide-like PAMP present on the surface of
microorganisms. On the other hand, injured tissue following mechanical or chemical exposure expresses damage-associated molecular patterns (DAMPs) that can be
recognized by the TLRs (El-Asrar 2012). This would initiate the release of inflammatory mediators to recruit more immune cells to the site in order to re-establish
homeostasis via remodeling or elimination of damaged cells or pathogens by complement activation and phagocytosis respectively.
Inflammatory response is broadly divided into acute and chronic on account of
its duration. Acute inflammation sets off once the irritant has been removed and the
body is adequately protected. However, chronic inflammation occurs when the
acute response fails to remove the noxious agent or if the tissue homeostasis is not
re-established, eventually leading to undesired immune reactions which may impair
tissue or organ function. Persistent inflammatory responses act as catalysts for the
development of many pathological manifestations. The link between inflammation
and the development of various pathogeneses is shown in Fig. 10.1.
Acute inflammation proceeds through vascular and cellular events. Vascular
events are the initial response to inflammatory stimuli and are induced by the
plasma-derived factors released by the injured tissue. Histamine and bradykinin are
the important mediators of vascular events. During vasodilation, volume of blood in
the area near the injury increases, resulting in redness (erythema). Vascular permeabilization facilitates influx of fluid and cells from the dilated capillaries into the site
of injury, resulting in edema. Endothelial gap formation facilitates neutrophil leakage, extravasation to the site of injury for phagocytosis, and clearance of the pathogen. Exudation of fluid activates kinin, clotting, and fibrinolytic systems which
facilitate the cellular events associated with acute inflammation. Cellular events
encompass the influx of leukocytes from the capillaries into the site of injury (leukocyte extravasation) facilitated by chemokines. They could accomplish phagocytotic clearance of the foreign component or damaged cells. However, in case of
chronic inflammatory response, either of the immune responses or both are activated in an attempt to counteract the cause of inflammation. Inflammation is initiated by the release of a vast array of mediators or effectors from injured tissues or
invading pathogens and immunologically activated cells.
10 Anti-inflammatory Molecules: Immune System Mediators