Immunology 9 - Immunology 9-The Complement System...

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Immunology 9-The Complement System Complement Heat labile component of plasma that complements killing of bacteria by antibodies Participates in both innate and adaptive immune responses A large number of proteins (48) that interact in a hub-like network as well as with other systems The function of complement proteins is to opsonise pathogens to combat infection= irreversibly mark pathogens by covalent linkage of complement components to surface Both plasma and serum have complement factors but serum doesn’t have clotting factors Proteins in several complement pathways function as zymogens: proteases that themselves have to be activated by other proteases IgM very efficient at activating classical complement pathway; less efficiently activated by IgG1, 2 and 3 Not activated by: IgA, IgE, IgD or IgG4 Nomenclature C designates proteins belonging to the classical pathway Number designates the name of the component; number is in order of discovery NOT activation Products of cleavage reactions are designated by adding a lower case letter as a suffix; ex C3a/b The complement system recognizes features of microbial surfaces and marks them for destruction by the deposition of C3b The 3 pathways are initiated in different ways: 1. Lectin pathway= initiated by soluble carbohydrate binding proteins (mannose binding lectin and the ficolins) that bind to particular carb structures on microbial surfaces; proteases associated with these recognition proteins then trigger the cleavage of complement proteins and activation of the pathway 2. Classical pathway= initiated when complement component C1 , which comprises a recognition protein (C1q) associated with proteases (C2r and C1s), either recognizes a microbial surface directly or binds to antibodies already bound to a pathogen 3. Alternative pathway= initiated by spontaneous hydrolysis and activation of the complement component C3 , which can then bind directly to microbial surfaces All 3 pathways converge at the central and most important step; when any of the pathways interact with a pathogen surface, an enzymatic activity called a C3 convertase is generated; each is a multisubunit protein with protease activity that cleaves complement component 3 (C3); C3 convertase is covalently bound to the pathogen surface, where it cleaves C3 to generate large amount of C3b (main effector molecule of the complement system) and C3a (a peptide that helps induce inflammation **cleavage of C3 leads directly or indirectly to all effector activities of the complement system: C3b binds covalently to the microbial surface and acts as an opsonin, enabling phagocytes that carry receptors for complement to take up and destroy the C3b-coated microbe; can also bind to the C3 convertases formed by the classical and lectin pathways, forming another multiunit enzyme= C5 convertase =cleaves C5 liberating the highly inflammatory peptide C5a and generating C5b (initiates the late events of complement
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This note was uploaded on 02/08/2012 for the course PATHOLOGY 3245 taught by Professor X during the Spring '11 term at UWO.

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Immunology 9 - Immunology 9-The Complement System...

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