Complement and Diseases.
-
Upload
maud-gibbs -
Category
Documents
-
view
229 -
download
0
description
Transcript of Complement and Diseases.
Complement and Diseases Main Points Three pathways of Complement
activation
Diseasesassociatedwithcomplement 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 Systemic lupus erythematosus,SLE Intracerebral
hemorrhage,ICH Inherited complement deficiencies Glomerulonephritis
Clinic symptoms Edema Hematuria
Albuminuria Hypertension Renaldisfunction Glomerulonephritis
Mechanism 1Heterophilic antigen,
such as hemolytic streptococcus ICformation 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 2IC
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 Pericarditis Pleurisy Lupus nephritis
Arthritis Anemia Systemic lupus erythematosus,SLE
Mechanism Auto-antibody: anti-nucleus antibody ICaggradation
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 C3aC5a
induce inflammation Intracerebral hemorrhage,ICH
Treatment Diminish inflammation Suppresscomplement activation
Inherited complement deficiencies
1C1C4 or C2deficiency usually causes IC disease, such as SLE,
Glomerulonephritis. 2C3H factor or I factordeficiency, pyogenic
bacteriuminfection 3C5C6C7 or C8deficiency, neisseriainfection
Inherited complement deficiencies
Treatment:correct complement deficiencies 1input purified deficient
component or fresh plasma 2promote 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 back