the complement

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• Section 5
• the complement
• system

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• Chapter 1 introduction

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Complementhistory

• Discovered in 1894 by Bordet
• It represents lytic activity of fresh serum
• Its lytic activity destroyed when heated at 56C
  for 30 min

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• A group of heat-labile proteins exist in normal
  plasma
• Mediate a set of activities
• Form the principal effector arm of the humoral
  immune system

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Component of complement system

• More then 30 protein in serum and on the cell
  surface
• Activated by 3 pathway
• Classical pathway
• Alternative pathway
• Lectin pathway

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Alternative pathway
Lectin pathway
Classical pathway
MBL MASP
C3b
C1 C4 C2
B factor Properdin D factor
C3
C5?C6?C7?C8?C9
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nomenclature

• ?Inherent components of the complement
• ? Regulatory proteins
• ? Complement receptors

? Other
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Inherent components
Regulatory proteins
C1-inh?I factor? H factor

• CR15?C3aR?C2aR?C4aR

Complement receptors
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• Chapter 2
• pathways of complement activation

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Three major pathways

• Classical pathway
• Mannan-binding lectin (MBL) pathway
• Alternative pathway

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Alternative pathway
Lectin pathway
Classical pathway
MBL MASP
C3b
C1 C4 C2
B factor Properdin D factor
C3
C5?C6?C7?C8?C9
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• C3 is a key component which is common to all
  three pathways
• The pathways proceed identically through binding
  of the terminal components
• Form a membrane attack complex
• Causes cell lysis

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Classical pathway

• Immune complex activate C1
• The whole procedure can factitiously divided into
  3 stages
• recognization stage
• activation stage
• terminal stage

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• Initiation
• Immune complex (Ag-Ab complex)
• a single molecule of IgM
• Two molecules of IgG of appropriate subclass
  (IgG1, IgG2, IgG3) bound side by side

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The mainly component
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The first component of the pathway

• C1 complex
• C1q
• Two C1r
• Two C1s

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recognization stage form C1s
Ag-Abcomplex
C1r
C1q
develops enzymatic activity
C1s
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activation stageform C3 convertase and C5
convertase
C4
C4aC4b
C1s
C2
C2aC2b
C3aC3b
C3
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The classical pathway
C4

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The classical pathway
C2
C4a

Mg
C4b
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The classical pathway
C2b
C4a

Mg
C3
C4b
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terminal stage

• Form the membrane attack
• complex (MAC)
• Cause cell lysis

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• C4b2a3b C5 ? C5bC5a
  ?C6?C7?C8?C9
  ? C5b6789n(MAC)
  ?
  cell lysis

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The lectin pathway

• MBL(mannan-binding lectin)pathway
• Participate components MBL?MASP?C4?C2 and C3
• MBL mannan binding lectin
• MASP MBL-associated serine protease

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MBL

• The initiating serum protein for the MBL pathway
• The structure is
  similar to C1q
• Recognize certain
  carbohydrates expressed on
  the surface of
  microorganisms

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MASP

• MBL-associated serine protease
• MASP-1
• MASP-2
• The structure is
  similar to C1r and
  C1q

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C4
C3
C2
bacteria
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Mannan-binding lectin pathway
C4
C2
MASP2
MASP
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The lectin pathway
C4
C4a C4b


C2
C2b C2a
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alternative pathway

• important in the innate immune system
• do not depend on Ab
• C3 convertase C3bBb
• C5 convertase C3bBb3b

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Components of thealternative pathway
D
C3
B
P
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abnormal
normal
inactivate
factor
factor
Foreign particle
factor
factor
inactivate
The alternative pathway
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C3 hydrolysis spontaneously
D
H2O
B
C3
C3
This C3b molecule has a very short half life
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This C3b is degraded rapidly
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This C3b is degraded rapidly
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If This C3b is not degraded .
D
P
B
C5
C3
C5 convertase
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Alternative pathway can recognize self and nonself
C3b
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C3-activation the amplification loop
D
B
C3
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C3-activation the amplification loop
D
B
C3
C3a
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C3-activation the amplification loop
D
B
C3
C3a
C3a
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C3-activation the amplification loop
C3a
C3a
C3a
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C3-activation the amplification loop
C3a
C3a
C3a
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• Terminal sequence and the
• membrane attack complex

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Components of the Terminal sequence
C6
C5
C 9
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• C5 convertase C5
  C5bC5a
• 
  C6?C7?C8?C9
• C5b6789n(MAC)
  
  
• damage the cell
  membrane
• cause the cell
  lysis

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C5 activation
C5
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MAC forming
C6
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• ???????????

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• Chapter 3
• regulation of complement system activation

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• Self regulation
• Fluid-phase regulators
• Cell-bound control proteins

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• Chapter 4
• biological consequences of complement
  activation

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Biologic effects

• cell lysis
• Opsonization and phagocytosis
• viral neutralization
• inflammation
• regulation of cells
• clearance of immune complex

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Cell lysis

• Form MAC
• Destroy the target cells

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Opsonization and phagocytosis

• Coating of the foreign particles with fragments
  of complement
• Prepared for phagocytosis
• C3b, C4b, iC3b

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viral neutralization

• Coating of the viruses with fragments of
  complement
• Block the viruses attaching to susceptible host
  cell
• C3b

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inflammation

• C3a, C4a, C5a
• anaphylatoxin
• smooth muscle contraction
• capillary leakage
• Be chemotactic for neutrophils and mononuclear
  phagocytes

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????
C3a?C5a ??????????
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regulation of cells

• Activate the binded cells
• Divide the binded cells

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clearance of immune complex

• C3b

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