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      The complement system: History, pathways, cascade and inhibitors

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          Since its discovery in the 19th century, the complement system has developed into a clinically significant entity. The complement system has been implicated in a variety of clinical conditions, from autoimmune diseases to ischemia-reperfusion injury in transplantation. This article charts the historical progress of our understanding of the complement system and provides a synopsis on the activation pathways and its inherent regulators.

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          Complement. Second of two parts.

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            Complement control protein factor H: the good, the bad, and the inadequate.

            The complement system is an essential component of the innate immune system that participates in elimination of pathogens and altered host cells and comprises an essential link between the innate and adaptive immune system. Soluble and membrane-bound complement regulators protect cells and tissues from unintended complement-mediated injury. Complement factor H is a soluble complement regulator essential for controlling the alternative pathway in blood and on cell surfaces. Normal recognition of self-cell markers (i.e. polyanions) and C3b/C3d fragments is necessary for factor H function. Inadequate recognition of host cell surfaces by factor H due to mutations and polymorphisms have been associated with complement-mediated tissue damage and disease. On the other hand, unwanted recognition of pathogens and altered self-cells (i.e. cancer) by factor H is used as an immune evasion strategy. This review will focus on the current knowledge related to these versatile recognition properties of factor H. Copyright 2010 Elsevier Ltd. All rights reserved.
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              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 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.

                Author and article information

                European Journal of Microbiology and Immunology
                Akadémiai Kiadó
                1 June 2012
                13 June 2012
                : 2
                : 2 ( otherID: K022535X4502 )
                : 103-111
                [ 1 ] University Hospital of Wales Cardiff Transplant Unit Cardiff UK
                [ 2 ] Cardiff University Institute of Molecular and Experimental Medicine, School of Medicine Cardiff UK
                [ 3 ] University Hospital of Wales Dept of Transplant Surgery Cardiff CF10 5NQ UK
                Review Articles

                Medicine,Immunology,Health & Social care,Microbiology & Virology,Infectious disease & Microbiology
                complement activation,complement system,complement cascade,complement inhibitors,complement history


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