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Complement system

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"Complement" describes a system of about 20 proteins, many of which are enzyme precursors. The principal actors in this system are 11 proteins designated C1 through C9, B, and D,
All these are present normally among the plasma proteins in the blood as well as among the proteins that leak out of the capillaries into the tissue spaces.
The enzyme precursors are normally inactive, but they can be activated mainly by the so-called classic pathway.

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  • C3 convertase C4b2b or C4b2a?????
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Complement system

  1. 1. ‫بسم اللة الرحمن الرحيم‬
  2. 2. 2
  3. 3. Complement System
  4. 4. Complement System for Antibody Action• "Complement" describes a system of about 20 proteins, many of which are enzyme precursors. The principal actors in this system are 11 proteins designated C1 through C9, B, and D,• All these are present normally among the plasma proteins in the blood as well as among the proteins that leak out of the capillaries into the tissue spaces.• The enzyme precursors are normally inactive, but they can be activated mainly by the so-called classic pathway.
  5. 5. ComplementSynthesis : in liver – appear in fetal circulation during 1st 13 W Function : Responsible for certain aspects of immune response and inflammatory response Activation : antigen-antibody complex or endotoxin, capsule series of proteins activated sequentially Inactivation: inhibitors in plasma (short lived) Biological effects: either beneficial or harmful to host
  6. 6. Complement pathwayA) Classical pathway: - Complement is activated by antigen –antibody complex (IgM or IgG) - Fc portion of the antibody form a binding site for C1q - The numerical sequence of the complement factors in the classic pathway is: C1, C4, C2, C3, C5, C6, C7, C8, C9
  7. 7. Complement ActivationClassical Pathway C1 C4 C2 C3 Alternative pathway C5 C6 C7 C8 C9 Membrane damage
  8. 8. Classic Pathway. The classic pathway is initiated by an antigen-antibody reaction. a specific reactive site on the "constant" portion of the antibody becomes uncovered, or "activated," and this in turn binds directly with the C1 molecule of the complement system, setting into motion a "cascade" of sequential reactions,, beginning with activation of the proenzyme C1 itself. The C1 enzymes that are formed then activate successively increasing quantities of enzymes in the later stages of the system, so that from a small beginning, an extremely large "amplified" reaction occurs.
  9. 9. proteins of the classical pathway• C1• C1 exists in blood serum as a molecular complex containing:• 1 molecules of C1q• 2 molecules of C1r• 2 molecules of C1s
  10. 10.  The constant regions of Antibody contain a binding site for C1q. (A single molecule of IgM is enough to initiate the pathway.
  11. 11.  Binding of C1q activates C1s and C1r. Activated C1s (a serine protease) cleaves two serum proteins: C4 is cleaved into a large fragment  C4b, which binds covalently to sugar residues on cell-surface glycoproteins,  and a smaller, inactive, fragment of C4a which diffuses away.
  12. 12. C2 is cleaved into • C2b, which binds noncovalently to a site on C4b, leaving a smaller, inactive, fragment of • C2a which diffuses away.The complex of C4b•2b is called "C3 convertase" because it catalyzes the cleavage of C3.
  13. 13. • C3• C3 is the most abundant protein of the complement system (~1.3 mg/ml).
  14. 14. • C4b•2b cuts C3 into two major fragments: – C3b, which binds covalently to glycoproteins scattered across the cell surface. – Macrophages and neutrophils have receptors for C3b and can bind the C3b-coated cell or particle preparatory to phagocytosis. This effect qualifies C3b as an opsonin.
  15. 15. – C3a This small fragment is released into the surrounding fluids. It can bind to receptors on basophils and mast cells triggering them to release their vasoactive contents (e.g., histamine). Because of the role of these materials in anaphylaxis, C3a is called an anaphylatoxin.
  16. 16. • Some of the C3b binds to molecules of C5 exposes them to cleavage by C4b•2b (which is thus a "C3/C5 convertase".)
  17. 17. • C5• Cleavage of C5 by the C3/C5 convertase initiates the assembly of a set of complement proteins that make up the membrane attack complex.
  18. 18. • C5b, which serves as the anchor for the assembly of a single molecule each of – C6; – C7, and – C8.• The resulting complex C5b•6•7•8 guides the polymerization of as many as 18 molecules of C9 into a tube inserted into the lipid bilayer of the plasma membrane. This tube forms a channel allowing the passage of ions and small molecules. Water enters the cell by osmosis and the cell lyses.
  19. 19. B) Alternative pathwayThis pathway is initiated by: * Bacterial endotoxin, polysaccharide capsule, aggregates of IgE and properdin * It starts at C3 then C5, C6, C7, C8, C9 * The complement compon. C1, C4, C2 are by-passed * Antibodies are not required to initiate activation of this pathway * This pathway provides a means of non-specific resistance
  20. 20. Classical pathway The classical pathway is activated at C1 and requires antibodies that have bound to antigens. The alternative pathway is activated when complement protein C3 becomes spontaneously active and combines with foreign substances Alternative pathway and factors B, D, and P.Activated Complement proteinsC3 – C7 promotephagocytosis,inflammation, andchemotaxis (attractimmune system cells).They can be activatedby either the classicalor alternative pathway. Complement Plasma proteins form membrane a membrane attack complex Complement proteins C5 – C9 (yellow) combine to form a hole in the plasma membrane of target cells, causing the cells to lyse.
  21. 21. selected Complement System s.flv
  22. 22. Thanks

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