Monday, November 15, 2010

Activation of immune system and inflammation mediators (from Holgate 2003)

The Human Immune System is an extremely sophisticated chemical signaling systems, with the capacity to produce almost unlimited variability within a homeostatic regulatory framework that is just being glimpsed. Innate and acquired immunity are mediated by a large number of systems and subsystems, including the complement system, chemokines, cytokines, lipid-signalling molecules, etc. Inflammation, the process of capillary dilation, smooth muscle contraction, and recruitment of immune cells, utilizes seven major pathways.

Cellular and Plasma Inflammation Mediators:

Plasma Inflammation Mediators

COX/LOX Lipid Inflammation Pathway

"It is unclear to what extent the nature of an inflammatory trigger dictates the type of mediator induced. In addition, many (but not all) mediators not only have direct effects on target tissues but also themselves induce the production of additional mediators.
It will be important to understand the logic underlying this hierarchy of mediators."(Medzhitov, 2008)

Seven types of Inflammation Mediators (Medzhitov, 2008):
1. Vasoconstrictive amines: histamine, serotonin
2. Vasoactive Peptides: Substance P, etc
3. Complement Fragments: C3a, C4a, C5a
4. Lipid Mediators: eicosanoids,
5. Cytokines: TNF, IL-1, IL-6, etc
6. Chemokines
7. Proteolytic enzymes

1. Baroody FM, Naclerio RM. Antiallergic effects of H1-receptor antagonists. Allergy. 2000;55(s64):17-27.
2. Holgate ST, Broide D. New targets for allergic rhinitis a disease of civilization. Nat Rev Drug Discov. 2003 November;2(11):903-915.
3. Medzhitov R. Origin and physiological roles of inflammation. Nature. 2008 July 24;454(7203):428-435.

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