Principles of Immunology Complement 2/7/06 “Nothing is to be more prized than the value of each day” Goethe.

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Presentation transcript:

Principles of Immunology Complement 2/7/06 “Nothing is to be more prized than the value of each day” Goethe

Word List  Complement fixation  Heat labile  Immune complexes  Opsonization  Proenzymes

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

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?

Effects of Complement  Cell lysis Ab dependent Ab independent  Opsonization  Inflammation  Clearance of Immune complexes  Viral neutralization

Complement Precursors  ~ 5% of serum globulin  Proenzymes (zymogens)-proteins or glycoproteins  Continuously circulate in inactive state  Source-hepatocytes, monocytes, macrophages, epithelial cells

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

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

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

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

Biological Effects of C Activation  Inflammation C3a, C5a  Opsonization C3b  Cell lysis Membrane attack complex (MAC) C5b-C9

Cell Receptors for C  CR1 Macrophages, neutrophils Binding of immune complexes  CR3/CR4 Macrophages, neutrophils Binding of immune complexes; enhanced phagocytosis

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

C Deficiencies  C3 deficiency Very severe  Other deficiencies in C components or inhibitors