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Principles of Immunology Complement 2/7/06 “Nothing is to be more prized than the value of each day” Goethe
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Word List Complement fixation Heat labile Immune complexes Opsonization Proenzymes
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History Bordet-Heat labile substance in the serum Ehrlich-Named it complement because it completes the action of lysis when coupled with antibody Wasserman-Complement fizxation(CF) test for syphilis
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CF Test Step 1-Mix unknown serum with Ag of known pathogen Step 2-Add Complement Step 3-Add Ab-coated RBCs to test system Possible outcomes: RBCs lyse RBCs don’t lyse Interpretation?
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Effects of Complement Cell lysis Ab dependent Ab independent Opsonization Inflammation Clearance of Immune complexes Viral neutralization
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Complement Precursors ~ 5% of serum globulin Proenzymes (zymogens)-proteins or glycoproteins Continuously circulate in inactive state Source-hepatocytes, monocytes, macrophages, epithelial cells
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Complement Components C1 through C9 Numbered in order of description, not sequence of action Enzymatic reaction triggered by one of three mechanisms Antibody-Antigen Microbial or non microbial foreign substances Mannose binding lectin
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Classical Pathway Adaptive immunity C1 binds to Ag-Ab complex Activated C1 cleaves C4 and C2 Formation of C3 convertase C3 is cleaved C5 is cleaved Sequential binding of C6-C9
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Alternative Pathway Innate immunity Spontaneous cleavage of C3 based on multiple initiators Requires Factors B and D Formation of C3 convertase (less stable) requires properdin
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MB Lectin Pathway Innate immunity MB Lectin bound to microbial cell wall components Follow-up binding of serine proteases This complex cleaves C4 and C2 much like activated C1
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Biological Effects of C Activation Inflammation C3a, C5a Opsonization C3b Cell lysis Membrane attack complex (MAC) C5b-C9
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Cell Receptors for C CR1 Macrophages, neutrophils Binding of immune complexes CR3/CR4 Macrophages, neutrophils Binding of immune complexes; enhanced phagocytosis
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Regulation of C Pre C3 convertase C1 inhibitor C4b binding protein Factor 1 Post C3 convertase Factor H DAF At level of MAC S protein MIRL
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C Deficiencies C3 deficiency Very severe Other deficiencies in C components or inhibitors
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