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Concepts
Complement Activation
Regulation of the Complement System
Biological Function of Complement
Concepts
1. Simple history of complement research
1890 Behring antitoxin
1894 Pfeiffer temperature sensitive component in serum
necessary for bacteriolysis
1894 Bordet alexin (1920 Nobel prize)
1894 Ehrlich complement Ab to cause bacterolysis
1907 Ferrata C1, C2
1912 Ritz C3
1926 Gorder C4
1969 Muller-Eberhard Classical pathway
Presumption:
1. classical pathway
2. alternative pathway
3. lectin pathway
Complement Activation
1. classical pathway
a. activator
IC (immune complex)
polymerizer (heparin, polynucleotide)
dextran sulfate
protein (CRP)
liposome
mitochondria of cardiac muscle
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.
C1q
c. activation stage
2. alternative pathway
a. activator
LPS
bacteria
zymosan
dextran
IgA
IgG4
IgE
2. alternative pathway
b. characteristics:
non-specific, rapid
distinguish self and non-self
C3b positive feedback
need a surface to stick or activate C3b
2. alternative pathway
c. activation stage
formation of C3bBb
1. Short half-life
2. Regulation protein
up-regulation: Properdin, C3Nef
down-regulation: C1INH, C4bBp, Hf,
If, DAF, CR1, MCP
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
Complement and Clinic
1. Complement deficiencies
2. Serum complement level and disease
3. Pathological damage by complement
4. Clinical application of complement
Diseases about Complement deficiencies