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Dr. M. Izad Sep 2014

The Complement System. Dr. M. Izad Sep 2014. To understand how the complement system works To determine the Role of Complement in the Innate & Acquired Immunity Regulation of complement system To understand the consequences of Deficiency of Complement. Objectives. History.

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Dr. M. Izad Sep 2014

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  1. The Complement System Dr. M. Izad Sep 2014

  2. To understand how the complement system works To determine the Role of Complement in the Innate & Acquired Immunity Regulation of complement system To understand the consequences of Deficiency of Complement Objectives

  3. History • Jules Bordet 1890s • Lysis of bacteria (VibrioCholerae) VibrioCholerae Sheep Antibody against VC sheep antiserum Lysis of bacteria Heating the antiserum No Lysis of bacteria Heated serum + Fresh serum without Ab Restore the ability of lysis • Hemolysis • Paul Ehrlich Complement “The activity of blood serum that completes the action of antibody”

  4. Complement ( C ) • Complement consists of a complex series of over 30 soluble & cell-bound Proteins. Many of which are enzymes (proenzyme/zymogen-proteinases). • The biological activities of this system affect both innate & acquired immunity. • They can bind to an antibody molecule or can act independently, to affect various aspects of the immune system.

  5. Complement Components are produced by: • Liver hepatocytes • Macrophages • Blood monocytes • Epitelial cells of gastrointestinal & genitourinary tracts

  6. Complement components are designated by: Neumerals (C1-C9) Letter symbols (e.g., factor D) Trivial names (e.g., homologus restriction factor) The smaller fragment resulting from cleavage of a component is designated “a” & the larger fragment designated “b” Those complexes that have enzymatic activation are designated by a bar over the number or symbol (e.g.,

  7. Complement Activation

  8. IgM, IgG1,2,3

  9. C1 Structure

  10. Figure 2-53 part 3 of 3

  11. Innocent bystander lysis

  12. Figure 2-35

  13. Bacteria (Salmonella, Listeria, Nisseria) • Fungi (Cryptococcus Neoformans, Candida Albicans • Viruses ( HIV)

  14. Figure 2-24

  15. Regulation of the Complement system

  16. Classical PathwayC1 inhibitor

  17. Classical & Lectin PathwaysC4bBp, CR1, MCPRegulators of complement activation (RCA) gene cluster CR1, MCP

  18. Alternative PathwayFactor H, CR1, MCPRegulators of complement activation (RCA) gene cluster CR1,MCP,

  19. Classical & Lectin & Alternative PathwaysDAF (CD55) C4bBp, CR1, Factor H C3bBb C3b

  20. Regulation at assembly of MACS protein

  21. Regulation at assembly of MACHomologous restriction factor(HRF) or CD59 /CD59

  22. Functions of Complement -Enveloped viruses: Herpesvirus, Measels/ Mumps, Influenza -Gram negative bacteria

  23. Complement Receptors

  24. Deficiency of Complement System

  25. C1q, C1r, C1s, C4,C2 homozygous deficiencies Immune Complex Disease such as systemic lupus erythematosus, vasculitis, glomerulonephritis Recurrent infections by pyogenic bacteria such as streptococci & staphylococci Classical Pathway • C1q, C1r, C1s, C4,C2 homozygous deficiencies

  26. Alternative Pathway • Factor D & properdin deficiencies Neisseria Infection

  27. MBLdeficiency • Relatievly common and results in serious pyogenic infections in neonates & children

  28. Homozygous deficiencies in components involved in the MAC formation Immune Complex Disease Recurrent Bacterial infections Recurrent meningococcal & gonococcal infections caused by Nisseria species Classical & Alternative Pathways C3 dificiency

  29. Congenital Deficiency of Complement Regulatory Proteins • C1 inhibitor deficiency Hereditary angioedema • DAF & CD59 deficiency Paroxysmal nocturnal hemoglobinuria

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