Key Complement System Proteins to Know for Immunobiology

The complement system is a crucial part of our immune defense, helping to identify and eliminate pathogens. It consists of various proteins that work together in pathways to enhance inflammation, opsonization, and cell lysis, ultimately protecting the body from infections.

1. C1q, C1r, C1s (C1 complex)

   • Initiates the classical pathway of complement activation by binding to antibodies on pathogen surfaces.
   • C1q is the recognition molecule, while C1r and C1s are serine proteases that become activated upon C1q binding.
   • Activation leads to the cleavage of C4 and C2, forming C3 convertase.

2. C2

   • A component of the classical and lectin pathways, cleaved by C1s to form C2a and C2b.
   • C2a combines with C4b to form the C3 convertase (C4b2a).
   • Plays a crucial role in the amplification of the complement cascade.

3. C3

   • Central component of the complement system, involved in all three pathways (classical, alternative, and lectin).
   • Cleaved into C3a and C3b, with C3b playing a key role in opsonization and forming C5 convertase.
   • Activation of C3 is a critical step in the complement cascade, leading to inflammation and pathogen clearance.

4. C4

   • Cleaved by C1s into C4a and C4b; C4b binds to the pathogen surface.
   • Forms part of the C3 convertase (C4b2a) in the classical and lectin pathways.
   • Involved in the opsonization process and the formation of the membrane attack complex.

5. C5

   • Cleaved by C5 convertase into C5a and C5b.
   • C5b initiates the assembly of the membrane attack complex (MAC) with C6, C7, C8, and C9.
   • C5a is a potent anaphylatoxin, promoting inflammation and recruiting immune cells.

6. C6

   • Binds to C5b to form the C5b6 complex, which is essential for the assembly of the MAC.
   • Stabilizes the C5b component and facilitates the recruitment of C7.
   • Plays a role in the lytic activity against pathogens.

7. C7

   • Binds to the C5b6 complex to form C5b67, which inserts into the pathogen membrane.
   • Facilitates the recruitment of C8 and C9 to form the complete MAC.
   • Important for the lysis of target cells.

8. C8

   • Binds to C5b67 and initiates the polymerization of C9.
   • Forms a pore in the target cell membrane, leading to cell lysis.
   • Plays a role in the stability of the MAC.

9. C9

   • The final component of the MAC, polymerizes to form a large pore in the target cell membrane.
   • Responsible for the lytic activity of the complement system.
   • Multiple C9 molecules can assemble to create a channel that disrupts cell integrity.

10. Factor B

    • A key component of the alternative pathway, binds to C3b to form the C3 convertase (C3bBb).
    • Cleaved by Factor D into Ba and Bb, with Bb remaining bound to C3b.
    • Amplifies the complement response by generating more C3b.

11. Factor D

    • A serine protease that cleaves Factor B when it is bound to C3b.
    • Essential for the formation of the alternative pathway C3 convertase (C3bBb).
    • Plays a critical role in the amplification loop of the complement system.

12. Properdin (Factor P)

    • Stabilizes the C3bBb complex, enhancing the alternative pathway's activity.
    • Increases the efficiency of complement activation on pathogen surfaces.
    • Acts as a positive regulator of the complement system.

13. Mannose-binding lectin (MBL)

    • A pattern recognition molecule that binds to mannose residues on pathogens.
    • Activates the lectin pathway of complement activation, similar to C1q in the classical pathway.
    • Facilitates opsonization and enhances phagocytosis of pathogens.

14. Ficolins

    • Similar to MBL, ficolins recognize specific carbohydrate patterns on pathogens.
    • Activate the lectin pathway of complement activation.
    • Play a role in immune defense by promoting opsonization and clearance of pathogens.

15. C3a and C5a (anaphylatoxins)

    • Small peptides released during complement activation that promote inflammation.
    • C3a recruits immune cells and enhances vascular permeability.
    • C5a is a potent chemotactic factor, attracting neutrophils and other immune cells to sites of infection.