Chapter 4
Introduction
Activation of Complement
Regulation of the Complement Activation
Biological function of the Complement
Ⅰ.Introduction
1.Discovery of the complement
2.Definition, components and
nomencleature of the
complement system
1.Discovery of the complement
bacteria (细菌)
Ab
immune serum
37℃
(免疫血清)
(Charles Bordet, 1894)
agglutination and bacteriolysis
(凝集)
( 溶菌)
56 ℃,30min
inactivated serum
(灭活血清)
agglutination but no bacteriolysis
fresh serum ?
bacteria
bacteriolysis
Conclusion:
新鲜血清中有两种成分参与溶菌 : 一种是耐
热的抗体, 另一种是不耐热、能辅助和补充抗体
溶菌作用的成分, 称为补体(complement)
Immune hemolysis
2.Definition , components
and nomenclature of the
complement system
A.Definition
补体是存在正常人和脊椎动物血清中一组经
活化后具有酶活性、可辅助和补充特异性抗体介
导溶菌溶血作用的蛋白质, 包括30多种可溶性蛋
白和膜结合蛋白,故称为补体系统
B.Components and nomenclature
B.Components and nomenclature
Inherent components of the complement

classical pathway:C1 (q、r、s) 、 C4 、C2

MBL pathway: MBL、serine protease
(甘露聚糖结合凝集素,
丝氨酸蛋白酶)

alternative pathway:B factor、D factor…

terminal pathway: C3、C5~C9
 Regulatory proteins
properdin、H factor、I factor 、 C4bp …
(备解素)
 Complement receptors
CR1~CR5、C2aR、C4aR…
 Other C3a、C3b; C3bBb and iC3b…
Ⅱ.Activation of the Complement
补体的激活是指补体的各个成分在激活物作用
下，以连锁的酶促反应依次被激活(也称为补体级
联反应),最终导致溶细胞效应的过程
1.Three pathways of complement
activation
 Classical pathway
 MBL pathway
 Alternative pathway
2.The common terminal pathway
 Classical pathway
activator Ag-Ab complex
condition

(IgG1,2,3 or IgM)
*every C1q must bind to at least of two Ig-Fc
fragments of IC CH3 of IgM/ CH2 of IgG
1 IgM molecule or 2 IgG molecules
*free or soluble antibody can’t activate the
complement
initiation C1(C1q) binds to Ig-Fc fragment of IC
activation of classical pathway

identification stage
activation stage
membrane attacking stage (terminal pathway)
•identification stage ---C1 identified the IgFc of the
IC and formation of C1 esterase
Ca2+
(IC)
暴露Fc段补体结合点
(C1酯酶)
与IgFc段
结合部位
C1s
C1s
Mg++
C1q---identification
C1r,C1s---catalysis
•activation stage
---formation of the
C3 convertase and
the C5 convertase.
•membrane attacking stage
 MBL Pathway
activator MBL (mannan binding lectin)
 initiation MBL combine with the pathogen-mannose

residue and serine protease
activation of MBL pathway

(similar to Classical pathway)
MBL
＋
＋
 Alternative Pathway
 activator
---LPS, polysaccharide, condense IgA and IgG4

Initiation
---activator directly activate alternative pathway
具蛋白酶活性
2.Common Terminal Pathway
(Membrane attacking stage)
---C5 convertase can split C5→→→→the membrane
attack complex(MAC) was form and cause the target
cell lysis.
C5 convertase
classical pathway
---C4b2b3b
C5a
C5转化酶
C5
alternative pathway
-- ---C3bnBb
MBL pathway
---C4b2b3b
p40图4-6
共同的末端途径
细胞溶解
(从激活物质、参与成分、 C3/C5转化酶及生物学作用做比较)
Ⅲ.Regulation of the
Complement Activation
1.Self regulation of the complement
---decay of C3 convertase, C5 convertase,
C4b, C3b, C5b……
2.The regulator factor: limit or enhance
the the process of the activation
---C1 inhibitor,I factor,MCP,H factor,CR1,
DAF,C4 binding protein,CD59,C8bp……
 Regulation of classical pathway
C1抑制分子
与C1rC1s结合
DAF
同C2竞争与C4b结合
结合
C4bp
CR1
裂解
+
失活
I因子
+
MCP
(membrane cofactor protein)
 Regulation of alternative pathway
竞争结合C3b
裂解
I因子
+
H因子,CR1
和MCP
抑制B因子
与C3b结合
H因子
解离
CR1,DAF
DAF:衰变加速因子)
 Regulation of the forming of the
membrane attack complex
CD59
阻碍C7C8与C5b~6结合
干扰C9与C8结合
C8bp
Ⅳ.Biological Function of the
Complement System
1.Mediate cytolysis
2.Biological effects mediated by
activated complement fragments
 Opsonization(调理作用)
 Cause inflammation
 Clear the immune complex
 Regulate the immune response