Complement: a unique innate immune sensor for danger signals

The complement (C) inflammatory cascade is part of the phylogenetically ancient innate immune response and is crucial to our natural ability to ward off infection. It has three critical physiologic activities: (i) defending against microbial infections by triggering the generation of a membranolytic...

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Bibliographic Details
Published in:Molecular immunology 2004-11, Vol.41 (11), p.1089-1098
Main Author: Gasque, Philippe
Format: Article
Language:English
Subjects:
Animals
Apoptosis
Biological Evolution
Carbohydrates
Clearance
Complement
Complement C1q - immunology
Complement C1q - physiology
Complement System Proteins - immunology
Complement System Proteins - physiology
Cytotoxicity
Humans
Immunity, Innate - immunology
Inflammation
Innate immunity
Membrane Glycoproteins - immunology
Membrane Glycoproteins - physiology
Phagocytosis
Phagocytosis - immunology
Receptors, Complement - immunology
Receptors, Complement - physiology
Repair
Scavenging
Signal Transduction - immunology
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Summary:The complement (C) inflammatory cascade is part of the phylogenetically ancient innate immune response and is crucial to our natural ability to ward off infection. It has three critical physiologic activities: (i) defending against microbial infections by triggering the generation of a membranolytic complex (C5b9 complex) at the surface of the pathogen and C fragments (named opsonins, i.e., C1q, C3b and iC3b) which interact with C cell surface receptors (CR1, CR3 and CR4) to promote phagocytosis. Soluble C anaphylatoxins (C4a, C3a and C5a) greatly control the local pro-inflammatory response through the chemotaxis and activation of leukocytes; (ii) bridging innate and adaptive immunity (essentially through C receptor type 2, CR2, expressed by B cells) and (iii) disposing of immune complexes and the products of the inflammatory injury (i.e., other danger signals, e.g., toxic cell debris and apoptotic corpses) to ensure the protection and healing of the host. The regulatory mechanisms of C are finely balanced so that, on the one hand, the deposition of C is focused on the surface of invading microorganisms and, on the other hand, the deposition of C on normal cells is limited by several key C inhibitors (e.g., CD46, CD55 and CD59). Knowledge of the unique molecular and cellular innate immunological interactions that occur in the development and resolution of pathology should facilitate the design of effective therapeutic strategies to fight selectively against intruders.
ISSN:0161-5890
1872-9142
DOI:10.1016/j.molimm.2004.06.011