Complement and Diseases

Main Points Three pathways of Complement activation Diseases associated with complement

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

Classical Pathway Generation of C3-convertase b Ca++ C1r C1s C1q C4

Classical Pathway Generation of C3-convertase C2b a C4a Ca++ C1r C1s C1q Mg++ C4b2a is C3 convertase C4b

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

Common terminal pathway b C5a C5 C3b C4b C2 a

Common terminal pathway Formation of MAC b C7

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

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

Spontaneous C3 activation Generation of C3 convertase D b i H2O B C3a b C3 C3 C3iBb complex has a very short half life

C3-activation the amplification loop If spontaneously-generated C3b is not degraded b D B C3a b C3b C3

C3-activation the amplification loop b D B C3a b C3b C3 Bb C3b C3a

C3-activation the amplification loop b D Bb B b C3a C3b C3b C3 Bb C3b C3a C3a

C3-activation the amplification loop Bb Bb C3b C3b C3b Bb C3b C3a C3a C3a

C3-activation the amplification loop Bb Bb C3b C3b Bb C3b C3a C3a C3a

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

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）

Glomerulonephritis Clinic symptoms Edema Hematuria（血尿） Albuminuria（蛋白尿） Hypertension Renal disfunction

Glomerulonephritis Mechanism 1、Heterophilic antigen, such as hemolytic streptococcus（溶血性链球菌） IC formation Complement activation

Glomerulonephritis MAC destroy nephron basement membrane stimulate visceral layer and mesangial cell to induce Inflammatory medium,

Glomerulonephritis such as Protease IL-1 Oxygen free group Hydrogen free group

Glomerulonephritis Treatment Avoid or reduce hemolytic streptococcus infection

Glomerulonephritis Mechanism 2、IC aggradation Complement activation C3a C5a induce inflammation

Glomerulonephritis Treatment Suppress complement activation Essentially, clearing IC, *plasma replacement therapy

Systemic lupus erythematosus,SLE Clinic symptoms: Fever Tetter（皮疹） Pericarditis Pleurisy Lupus nephritis Arthritis Anemia

Systemic lupus erythematosus,SLE Mechanism Auto-antibody: anti-nucleus antibody IC aggradation

Systemic lupus erythematosus,SLE Clinic symptoms: Fever Tetter Pericarditis Pleurisy Lupus nephritis Arthritis Anemia

Systemic lupus erythematosus,SLE Treatment Glucocorticoid Immune inhibitor

Intracerebral hemorrhage,ICH After ICH auto-antigen(myelin sheath) complement activation C3a、C5a induce inflammation

Intracerebral hemorrhage,ICH Treatment Diminish inflammation Suppress complement activation

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

Inherited complement deficiencies Treatment: correct complement deficiencies 1、input purified deficient component or fresh plasma 2、promote the expression of deficient component (gene engineering)

Thank you! Ji Xiaopeng Yang Linlin Zuo Bo Zhang Dejian Ni Lei Ma Chao Zhang Xianfei Cheng Linggang

Clearing immune complex

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