1. The Complement System Concepts Complement Activation
Regulation of the Complement System
Biological Function of Complement

2. 1. Simple history of complement research
Concepts
1. Simple history of complement research
Behring antitoxin
Pfeiffer temperature sensitive component in serum
necessary for bacteriolysis
Bordet alexin (1920 Nobel prize)
Ehrlich complement Ab to cause bacterolysis
Ferrata C1, C2
Ritz C3
Gorder C4
Muller-Eberhard Classical pathway

3. antiserum to the bacterium normal human/Guinea pig serum
1895 Bordet: the experiment of the lysis of
Vibrio cholerae
antigen (bacteria)
antiserum to the bacterium
normal human/Guinea pig serum
results
fresh
old
agglutination
lysis
Vibrio cholerae + -

4. Presumption:
There is a component in the fresh serum that helps the antibody to lyse the bacteria.
The chemical property of this component is not stable.
This component is not antigen specific.

5. The complement is a group of temperature sensitive protein existing in the serum and tissue fluid of human and vertebrate.
After activated, they have enzymatic activity.
They are the major molecules of the innate immune system.

6. 2. Components of the Complement System
(1) Complement Components: C1-9, MBL , SP , Bf , Df
(2) Regulatory Proteins: Properdin , C1INH , C4bBp , Hf, If , CR1 , Sp
(3) Complement Receptor: CR1-CR5 , C2aR , C3aR , C4aR

7. Complement Components involved in the classical pathway
(the components were named in order of their discovery)

8. 3. Denomination of the components of the complement system
With enzymatic activity after activation: C1, C4b2b
Peptide fragments formed by activation of a component: C3a, C3b (the smaller fragment is designated “a” and the larger fragment designated “b”)
Inactivated components: iC2a
Factors: B, P (capitalization)

9. 4. Basic Characteristics of Complement
The complement components interact in a highly regulated cascade.
Complement serves by amplifying the response: C1q, C3 convertase
Unstability: 56°C, 30min
Dualism of the functions: physiological functions, pathological functions
Restriction of reaction: easy to be inactivated, antibody, suppression component

10. Complement Activation
1. classical pathway
2. alternative pathway
3. lectin pathway

11. Complement Activation
1. classical pathway
a. activator
IC (immune complex)
polymerizer (heparin, polynucleotide)
dextran sulfate
protein (CRP)
liposome
mitochondria of cardiac muscle

12. b. activation condition
1. classical pathway
b. activation condition
The formation of an antigen-antibody complex induces
conformational changes in the Fc portion of the Ab molecule
that expose a binding site for the complement.
C1 binds to exposed C1q-binding sites in the CH2 domain of IgG1-3 or the CH3 domain of IgM.
C1 binds to at least two Fc portions of Ab.

15. C1q
(1) the biggest molecular weight, composed of 18 polypeptide chains that associate to form six collagen-like triple helical arm
(2) the only component of complement that circulate in the serum in functionally active forms
(3) For activation, it need to bind to at least two IgG or one IgM and need the presence of Ca2+.
(4) Free or soluble Ab can not bind to the complement; the formation of an antigen-antibody complex induces
conformational changes in the Fc portion of the Ab molecule.

17. 1. classical pathway
c. activation stage
recognition stage: IC-C1
activation stage: C1s→C4, C2→C3, C5
attack stage: C5b→C5678(9)n (MAC)

22. Complement Activation
2. alternative pathway
a. activator
LPS
bacteria
zymosan
dextran
IgA
IgG4
IgE

23. 2. alternative pathway b. characteristics: non-specific, rapid
distinguish self and non-self
C3b positive feedback
need a surface to stick or activate C3b

24. 2. alternative pathway c. activation stage formation of C3bBb
activation stage C3→C5
attack stage: C5b→C5678(9)n (MAC)

26. alternative pathway

27. Complement Activation
3. lectin pathway, MBL
a. activator: MASP (MBL:SP)
b. activation stage
formation of MASP: cleave C4, C2
activation stage: C3→C5
attack stage: C5b→C5678(9)n (MAC)

28. lectin pathway

29. Overview of the complement activation pathways.

30. membrane attack complex, MAC
Composition: C5b678 (9)n , C9
Size: nm inner diameter
Effects: This complex forms a large channel
through the membrane of the target cell, enabling ions and small molecules to diffuse freely across the membrane.

34. Regulation of the Complement System
1. Short half-life
2. Regulation protein
up-regulation: Properdin, C3Nef
down-regulation: C1INH, C4bBp, Hf,
If, DAF, CR1, MCP

35. Regulation of the Complement System

36. Biological Function of Complement
1. bacteriolysis, cytosis
2. function of complement fragments
a. opsonization: C3b, iC3b, C4b
b. mediator of inflammation: C3a, C4a, C5a
c. kinin: C2a, C5a
d. chemotaxis: C3a, C5a, C567
3. C-dependent virolysis
4. clean up IC: interfere with the formation of IC, IC-C3b-CR1-RBC
5. immunological regulation: C3, CR1, CR2, C3b

39. Complement and Clinic 1. Complement deficiencies
2. Serum complement level and disease
3. Pathological damage by complement
4. Clinical application of complement

40. Diseases about Complement deficiencies
Proteins in defect Functions influenced Diseases
C1, C2 , C deficiency in cleanup of IC SLE, pyogenic infection
deficiency in the activation of
classical pathway
C inability of cleanup of IC SLE, pyogenic infection
complement activation glomerular nephritis
C1INH loss of control in the production hereditary angiodysplasia
of inflammatory mediators
factor H loss of control in the activation SLE, pyogenic infection
of alternative pathway glomerular nephritis
low concentration of C3 in the serum
DAF, CD cytotoxic function of complement paroxysmal nocturnal
to host cell hemoglobinuria
CR deficiency in adhesion of PBMC infection (aeruginosus Bacillus,
pseudomonad etc.)

41. *** Definition, basic characteristics and components of complement
*** Characteristics of complement activation and the sameness and differentia of three complement activation pathways
** Biological Function of Complement
** Regulation of the Complement System and its significance
* Key biological significance of complement receptor and membrane-binding protein
* Relation between complement system and diseases