4. 医学分子生物学complement.pdf

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The Complement System 1. Introduction 2. Activation 3. Regulation 4. Complement receptors 5. Functions 1. Introduction to the complement system complement system It is an ancient but important defence system Approximate 30 proteins forming one of the major defence systems in the body, that are normally inactive but become activated under certain circumstances • Accounting for ~10% of serum proteins, C3 is the predominant component. • Sensitive to physical and chemical factors, the complement activity can be inactivated by incubation at 56℃for 30 min • Most complement components are produced by hepatocytes and macrophages Complement components 2. Complement activation Complement doesn’t function until being activated 2.1. Activation pathways 2.1.1 Classical 2.1.2. MBL 2.1.3. Alternative 2.2. Terminal stage of activation All 3 pathways have a terminal activation in common — formation of the MAC 2.1. Activation pathways There are 3 pathways - differ in how C3 convertase is generated • Classical pathway - activation by antibody-antigen complexes (adaptive) • MBL pathway - activation by carbohydrates present on microbes in absence of Ig (innate) • Alternative pathway - activation by microbes’ ‘protected’ surface in absence of Ig (innate) 2.1.1. Classical pathways of complement activation The classical pathway is activated by immune complexes This activation pathway begins with the C1q binding to the Fc part of antibody (IgM and IgG) attached to antigens. Classical pathway starts from the C1q binding to antigen-antibody complex Activation of complement by IgG and IgM antibodies Classical pathway of complement activation Classical pathways of complement activation • After formation of antigen-antibody complex, and C1q binds to the Fc fragment of the antibody

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