1. complement system 补体系统 IMMUNOLOGY Qingqing Wang
Institute of Immunology
Zhejiang University School of Medicine

2. Complement
Introduction
Activation of the Complement System 
Regulation of complement activation
Biological function of complement system

3. Discoverer of Complement
Jules Bodet ( ),
Discoverer of Complement
1894 Bordet 发现绵羊抗霍乱血清能够溶解霍乱弧菌，加热56℃ 30 min 阻止其活性；加入新鲜非免疫血清可恢复其活性。
1919 Nobel Prize
百日咳杆菌

4. Complement

5. Introduction Complement Complement (C)
A group of serum proteins involved in the control of inflammation, the activation of phagocytes and the lytic attack on cell membranes.
This activity is destroyed (inactivated) by heating serum at 56C for 30 minutes .
Complement System 
consists of a large number of proteins which become enzymes after being activated.

6. Proteins of the Complement System
Activation proteins
2. Regulatory proteins
3. Complement receptor

7. b是大片段，a是小片段 Abul K. Abbas, Adrew H. Lichtman, Shiv Pillai
b是大片段，a是小片段 Abul K. Abbas, Adrew H. Lichtman, Shiv Pillai. Cellular and Molecular Immunology. Saunders ELSEVIER, 6th edition 医学免疫学，人民卫生出版社，第四版 第五版… C2特殊，C2a是大片段

8. Activation Proteins Classical pathway: C1q, C1r, C1s, C4, C2
Complement
Activation Proteins
Classical pathway: C1q, C1r, C1s, C4, C2
MBL pathway: MBL, MASP
Alternative pathway: factor B, D
Terminal pathway: C3, C5, C6, C7, C8, C9

9. Regulatory Proteins Complement receptor
C1INH, C4bp, factor I, factor H
S protein, membrane cofactor protein
decay-accelerating factor (DAF) …
Complement receptor
CR1~CR5, C3aR, C2aR, C4aR…

10. II. Complement producing cells
Liver hepatocytes
Monocytes/Macrophages
Epithelial cells

11. C-----complement C1, C2, C3, C5 a-----small fragment C2a, C3a
Notation
C-----complement C1, C2, C3, C5
a-----small fragment C2a, C3a
b-----large fragment C2b, C3b, C5b
¯-----activated (enzyme) C1
i-----inactivated iC3b

12. Activation of the complement system
Classical pathway
MBL pathway
MBL: mannan-binding lectin
3. Alternative pathway

13. Classical pathway Complement A suitable Ab bound to Ag, Ag-Ab complex
C1, C4, C2 and C3, Ca++ and Mg++ cations
1. C1 activation
2. C4 and C2 activation (generation of C3
convertase)
3. C3 activation (generation of C5
4. Generation of C5 convertase marks the
end of the classical pathway

14. Downloaded from: StudentConsult (on 1 June 2006 04:16 PM)
© 2005 Elsevier

15. Activators Complement
Activation of this pathway may occur via Ag-Ab complex (immune complex, IC) or by aggregated Ig.
IgG (IgG1,IgG3) and IgM are most efficient in reacting with complement.
Only one molecule of IgM is required, whereas at least two molecules of IgG are needed.
Soluble antibody can’t activate complement

16. Three steps 1. Recognition ( C1 activation )
The components involved：C1q, C1r, C1s
Ag + Ab→IC→bind C1q→C1r→C1s →C1
2. Activation
The components involved: C4, C2 and C3
(1) C4 and C2 activation, generation of C3 convertase
(2) generation of C5 convertase
3. Attack (terminal pathway)
The components involved: C5, C6, C7, C8, C9
the membrane attack complex (MAC): C5b6789

17. Complement
Classical pathway
Ca++
C1 molecule

18. Downloaded from: StudentConsult (on 1 June 2006 04:16 PM)
© 2005 Elsevier

19. Complement
Classical pathway
Ca++

20. Complement
Ag-Ab complex
C3 convertase
C5 convertase
Classical pathway

21. Downloaded from: StudentConsult (on 1 June 2006 04:16 PM)
© 2005 Elsevier

22. Alternative pathway
Activators：bacterial lipopolysaccharides (endotoxin), certain complex polysaccharides
normal: Circulating plasma C3 undergoes spontaneous hydrolysis of its thioester bond to form a conformationally altered species called C3(H2O). Once the thioester group has opened, C3(H2O) acts like C3b.
C3→C3a
↓ D
C3b+B→C3bB→C3bBb (C3 convertase) →be dissociated
↑ ↑-
I I/H
abnormal:
no factor I and H on the surface of bacterial
C5 convertase :C3bBb3b or C3bnBb

23. 1.It is rather different from the MBL and classical pathway.
Complement
Alternative pathway
1.It is rather different from the MBL and classical
pathway.
2. no C1,C4 and C2 involved
factor B and factor D involved
3. the presence of suitable activator surfaces,such as
bacterial and fungal cell walls.
4. C3b: from the classical pathway; spontaneous
produced C3b

24. Complement
Alternative pathway

25. alternative pathway characters
1. It can recognize “self” and “non-self”
2. The amplification loop

26. MBL pathway ↓ ↓ Activators：MBL (like C1q)
MBL recognizes certain carbohydrates expressed on the surface of microorganisms. ↓
MBL activate two MBL-associated serine proteases
MASP-1 and MASP-2.
↓ ↓
cleaves C cleaves C4 and C2 to
activate the alternative generate the C3 convertase (C4b2b )
pathway directly

27. Activation of the Complement System
MBL pathway
When MBL binds to terminal mannose groups on bacterial carbohydrates, it activates MASP-1 and MASP-2, which go on to activate the classical pathway in an antibody-independent fashion.

28. Complement
MBL pathway

29. Downloaded from: StudentConsult (on 1 June 2006 04:16 PM)
© 2005 Elsevier

30. The Complement Pathways
Lectin Pathway
MBL
MASP 1,2,3
Classical Pathway
C1q C C C C5 to C9 Lysis
C1r,C1s
Alternative Pathway
C3 (H2O), C3b
Factors D, B, Properdin

31. Activation of the Complement System
Terminal pathway:MAC(membrane attack complex)

32. Activation of the Complement System
Terminal pathway

34. Downloaded from: StudentConsult (on 1 June 2006 02:08 PM)
© 2005 Elsevier

35. 不同途径补体系统激活的比较 经典途径 MBL途径 旁路途径 免疫复合物 病原体甘露糖残基 病原体表面 C1、C4、C2 MASP、C4、C2
C3、B、D
C3转化酶
C5转化酶
攻膜复合体

36. Regulation of complement activation
1.Self-regulation
C4b2b C3bBb C4b C3b C5b
2.Control proteins
classical pathway:C1INH C4bp I MCP
DAF
alternative pathway: H I CR1 DAF P
formation of MAC: C8bp CD59

37. Downloaded from: StudentConsult (on 1 June 2006 04:16 PM)
© 2005 Elsevier

38. Regulation of complement activation

39. C1IHN缺陷引起血管神经性水肿

40. Regulation of complement activation

41. Regulation of complement activation

42. Regulation of complement activation

43. Regulation of complement activation

44. Biological function of complement system
1. complement mediates anti-infection immunity
(1) Lysis of cell or microorganisms
(2) opsonization
(3) inflammation

45. Downloaded from: StudentConsult (on 1 June 2006 04:16 PM)
© 2005 Elsevier

46. (1)complement mediated lysis of cells

47. 溶菌
溶细胞
补体的溶细胞作用

48. C3a
C5a
过敏介质
肥大细胞
补体的过敏毒素作用

49. 单核-巨噬细胞 血管
中性粒细胞
C5a
C567 组织
C3a
补体的趋化作用

50. 免疫复合物
C3b受体
红细胞
补体的免疫黏附作用

51. 清除免疫复合物

52. 补体的调理作用 细菌
C3b受体
吞噬细胞

53. 补体调理杀菌作用

54. 补体系统各成分的生物学作用 C1q——识别免疫复合物、识别病毒膜蛋白 C4a——过敏毒素 C4b——组成C3、C5转化酶、参与免疫粘附
Ba——参与免疫调节
Bb——组成C3、C5转化酶
补体系统各成分的生物学作用

55. function: enhance phagocytosis
complement
(2) opsonization
opsonin: C3b, C4b, iC3b
cell: phagocyte
receptor: CR1, CR3, CR4
function: enhance phagocytosis

57. (3) inflammatory response symptoms: redness, swelling,
complement
(3) inflammatory response
symptoms: redness, swelling,
heat and pain
inflammation mediators
anaphylatoxins: C5a, C3a, C4a
chemoattractant: C5a

58. 2. Complement maintains homeostasis
clearance of IC (immune complex): C3b
elimination of apoptotic cells: C1q, C3b, iC3b

59. 3. Complement mediates adaptive immunity
(1) Participates in the induction of immune response (CD19/CD21/CD81on B cells)
(2) Participates in the proliferation and
differentiation of immune cells (B cells)
(3) Participates in the effector function of immune
response (complement fixing Ab)
(4) Participates in immune memory (through FDC)
4. Complement interacts with other
enzyme systems

60. Thanks for Your
attention!