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Complement system
Muthubharathi
Functions of cytokines
• Lysis of cell, bacteria and virus
• Opsonisation – phagocytosis
• Binds to specific receptors on the cell and triggers the cellular
function like inflammation
• Remove immune complexes and deposit them into spleen and liver
Complement components
• Produced by liver hepatocytes rarely by blood monocytes, tissue macrophages and
epithelial cells of gastrointestinal and genitourinary track
• Made up of Proteins and glycoproteins
• Inactive forms are called proenzymes or zymogens which are circulate in the blood
Numerical – C1-C9
Letter symbol – factor D
Trivial name – homologous restriction factor
• Peptide fragments formed by the activation of complements are denoted by small
letters (Eg., C3a, C3b whereas C2 is exception C2a is larger)
• Larger fragments bind to the target site and smaller fragments diffuse near the site
and triggers inflammation
• Complexes have enzyme activity are denoted by bars(e.g., C4b2a, C3bBb).
Activation of complement components
• Classical pathway
• Alternate pathway or lectin pathway
Classical pathway
• Begins with the formation of antigen-antibody complexes or binding
of antibody with antigen in bacterial cell
• Activation – IgM and classes of IgG (IgG1, IgG2, IgG3)
• Initially activated components – C1, C2, C3 and C4 which are inactive
form in plasma
• Ag-Ab complex induces confirmatory changes in Fc portion of IgM
and that expose a binding of C1 component
• C1 component
Macromolecule in plasma
Consists of C1q and two molecules each of C1r and C1s together in the complex of C1qr2s2
Ca2+
C1q- 18 peptides which forms six collagen like triple helical forms
C1r and C1s monomer consists of catalytic domain
C1 binds with Fc portion through C1q heads
IgM has 3 binding site of C1q but due to rotation of IgM, C1q binding sites are not exposed
IgG has single binding site for C1q, thus its binding needs two IgG.
Thus single molecule of IgM binds to RBC and lyse them and then activates complement cascade
activity
Nearly 1000 molecules of IgG are required to initiate the binding of C1q
Cont
• Binding of C1to Fc make changes in C1r , which converts into active
serine protease enzyme
• C1r cleaves C1s
• C1s has two substrase C4 and C2
• C4 – glycoprotein and 3 polypeptide chain ,  and 
Complement system
Complement system

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Complement system

  • 2. Functions of cytokines • Lysis of cell, bacteria and virus • Opsonisation – phagocytosis • Binds to specific receptors on the cell and triggers the cellular function like inflammation • Remove immune complexes and deposit them into spleen and liver
  • 3.
  • 4. Complement components • Produced by liver hepatocytes rarely by blood monocytes, tissue macrophages and epithelial cells of gastrointestinal and genitourinary track • Made up of Proteins and glycoproteins • Inactive forms are called proenzymes or zymogens which are circulate in the blood Numerical – C1-C9 Letter symbol – factor D Trivial name – homologous restriction factor • Peptide fragments formed by the activation of complements are denoted by small letters (Eg., C3a, C3b whereas C2 is exception C2a is larger) • Larger fragments bind to the target site and smaller fragments diffuse near the site and triggers inflammation • Complexes have enzyme activity are denoted by bars(e.g., C4b2a, C3bBb).
  • 5. Activation of complement components • Classical pathway • Alternate pathway or lectin pathway
  • 6. Classical pathway • Begins with the formation of antigen-antibody complexes or binding of antibody with antigen in bacterial cell • Activation – IgM and classes of IgG (IgG1, IgG2, IgG3) • Initially activated components – C1, C2, C3 and C4 which are inactive form in plasma • Ag-Ab complex induces confirmatory changes in Fc portion of IgM and that expose a binding of C1 component
  • 7. • C1 component Macromolecule in plasma Consists of C1q and two molecules each of C1r and C1s together in the complex of C1qr2s2 Ca2+ C1q- 18 peptides which forms six collagen like triple helical forms C1r and C1s monomer consists of catalytic domain C1 binds with Fc portion through C1q heads IgM has 3 binding site of C1q but due to rotation of IgM, C1q binding sites are not exposed IgG has single binding site for C1q, thus its binding needs two IgG. Thus single molecule of IgM binds to RBC and lyse them and then activates complement cascade activity Nearly 1000 molecules of IgG are required to initiate the binding of C1q
  • 8. Cont • Binding of C1to Fc make changes in C1r , which converts into active serine protease enzyme • C1r cleaves C1s • C1s has two substrase C4 and C2 • C4 – glycoprotein and 3 polypeptide chain ,  and 