1. The Complement System
Dr. M. Izad
Oct 2009

2. Objectives 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

3. Lysis of bacteria (Vibrio Cholerae) Hemolysis Paul Ehrlich
History
Jules Bordet 1890s
Lysis of bacteria (Vibrio Cholerae)
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 fromcleavage 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

16. Innocent bystander lysis

19. Figure 2-35

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

23. Figure 2-24

24. Regulation of the Complement system

25. Classical Pathway C1 inhibitor

26. Classical & Lectin Pathways C4bBp, CR1, MCP

27. Alternative Pathway Factor H, CR1, MCP

28. Classical & Lectin & Alternative Pathways DAF (CD55)
C4bBp, CR1,
Factor H
C3bBb
C3b

29. Regulation at assembly of MAC S protein

30. Regulation at assembly of MAC Homologous restriction factor(HFR) or CD59

31. Functions of Complement

32. Complement Receptors

35. Deficiency of Complement System

36. Classical Pathway 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
C1q, C1r, C1s, C4,C2 homozygous deficiencies
C1q, C1r, C1s, C4,C2 homozygous deficiencies

37. Factor D & properdin deficiencies
Alternative Pathway
Factor D & properdin deficiencies
Neisseria Infection

38. Classical & Alternative Pathways
Homozygous deficiencies in components involved in the MAC formation
Immune Complex Disease
Recurrent Bacterial infections
C3 dificiency

39. Congenital Deficiency of Complement Regulatory Proteins
C1 inhibitor deficiency
Hereditary angioedema
DAF & CD59 deficiency
Paroxymal nocturnal hemoglobinuria