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Principles of Immunology Complement 2/7/06

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

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Principles of Immunology Complement 2/7/06

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  1. Principles of ImmunologyComplement2/7/06 “Nothing is to be more prized than the value of each day” Goethe

  2. Word List • Complement fixation • Heat labile • Immune complexes • Opsonization • Proenzymes

  3. 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

  4. 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?

  5. Effects of Complement • Cell lysis • Ab dependent • Ab independent • Opsonization • Inflammation • Clearance of Immune complexes • Viral neutralization

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

  7. 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

  8. 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

  9. 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

  10. 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

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

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

  13. 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

  14. C Deficiencies • C3 deficiency • Very severe • Other deficiencies in C components or inhibitors

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