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Complement and Diseases
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Main Points Three pathways of Complement activation
Diseases associated with complement
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Pathways of complement activation
CLASSICAL PATHWAY MBL PATHWAY ALTERNATIVE PATHWAY antibody dependent antibody independent Formation of C3 convertase and C5 convertase activation of C5 Common Terminal Pathway
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Classical Pathway Generation of C3-convertase
b Ca++ C1r C1s C1q C4
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Classical Pathway Generation of C3-convertase
C2b a C4a Ca++ C1r C1s C1q Mg++ C4b2a is C3 convertase C4b
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Classical Pathway Generation of C5-convertase
C2b C4a Ca++ C1r C1s C1q C3a b C4b2a3b is C5 convertase; it leads into the Common Terminal Pathway Mg++ C4b C3 C2 a
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Common terminal pathway
b C5a C5 C3b C4b C2 a
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Common terminal pathway Formation of MAC
b C7
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Common terminal pathway: MAC insertion into cell membrane
9 C 9 C 9 C 9 C 9 C 9 C 9 C 9 C 9
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MBL pathway C4b C4a C2b C2a C4b2a is C3 convertase; it will lead to the generation of C5 convertase C4b C4 C2a C2 MASP2 MASP1 MBL
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Spontaneous C3 activation
Generation of C3 convertase D b i H2O B C3a b C3 C3 C3iBb complex has a very short half life
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C3-activation the amplification loop
If spontaneously-generated C3b is not degraded b D B C3a b C3b C3
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C3-activation the amplification loop
b D B C3a b C3b C3 Bb C3b C3a
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C3-activation the amplification loop
b D Bb B b C3a C3b C3b C3 Bb C3b C3a C3a
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C3-activation the amplification loop
Bb Bb C3b C3b C3b Bb C3b C3a C3a C3a
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C3-activation the amplification loop
Bb Bb C3b C3b Bb C3b C3a C3a C3a
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Functions of complement system
Activate mast cells Classic pathway Alternative pathway C3 C3b C3a Activate phagoctyes Opsonization Clearing IC Kill target cells C5a C5 C5b-9 Functions of complement system MBL pathway MAC
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Diseases associated with complement
Glomerulonephritis（肾小球肾炎） Systemic lupus erythematosus,SLE （系统性红斑狼疮） Intracerebral hemorrhage,ICH（脑出血） Inherited complement deficiencies （遗传性补体缺陷）
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Glomerulonephritis Clinic symptoms Edema Hematuria（血尿）
Albuminuria（蛋白尿） Hypertension Renal disfunction
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Glomerulonephritis Mechanism 1、Heterophilic antigen,
such as hemolytic streptococcus（溶血性链球菌） IC formation Complement activation
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Glomerulonephritis MAC destroy nephron basement membrane
stimulate visceral layer and mesangial cell to induce Inflammatory medium,
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Glomerulonephritis such as Protease IL-1 Oxygen free group
Hydrogen free group
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Glomerulonephritis Treatment Avoid or reduce
hemolytic streptococcus infection
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Glomerulonephritis Mechanism 2、IC aggradation Complement activation
C3a C5a induce inflammation
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Glomerulonephritis Treatment Suppress complement activation
Essentially, clearing IC, *plasma replacement therapy
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Systemic lupus erythematosus,SLE
Clinic symptoms: Fever Tetter（皮疹） Pericarditis Pleurisy Lupus nephritis Arthritis Anemia
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Systemic lupus erythematosus,SLE
Mechanism Auto-antibody: anti-nucleus antibody IC aggradation
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Systemic lupus erythematosus,SLE
Clinic symptoms: Fever Tetter Pericarditis Pleurisy Lupus nephritis Arthritis Anemia
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Systemic lupus erythematosus,SLE
Treatment Glucocorticoid Immune inhibitor
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Intracerebral hemorrhage,ICH
After ICH auto-antigen(myelin sheath) complement activation C3a、C5a induce inflammation
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Intracerebral hemorrhage,ICH
Treatment Diminish inflammation Suppress complement activation
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Inherited complement deficiencies
1、C1、C4 or C2 deficiency， usually causes IC disease, such as SLE, Glomerulonephritis. 2、C3、H factor or I factor deficiency, pyogenic bacterium（化脓性细菌）infection 3、C5、C6、C7 or C8 deficiency, neisseria（萘瑟菌）infection
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Inherited complement deficiencies
Treatment: correct complement deficiencies 1、input purified deficient component or fresh plasma 2、promote the expression of deficient component (gene engineering)
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Thank you! Ji Xiaopeng Yang Linlin Zuo Bo Zhang Dejian Ni Lei Ma Chao
Zhang Xianfei Cheng Linggang
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Clearing immune complex
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