Chapter 7: The Complement System

Study Notes

Comprised of approximately 20 proteins, including C1, C2, and C3, which exist in an inactive state in the plasma and must be cleaved to form active enzymes.

Synthesis occurs in the liver, intestinal cells, and macrophages.
Activation occurs sequentially in a cascading manner, with each protein activating the next protein in the sequence.
Complement activation can occur through the classical, lectin, or alternative pathways, all leading to the production of C3b.

Classical Pathway:
- Initiated by antigen-antibody complexes, specifically IgG and IgM.
- Activated by the binding of the Fc portion of the antibody molecule to specific cellular antigens.
- C1 is activated, followed by C4, C2, and C3, leading to the formation of the membrane attack complex (C5b6789).
Alternative Pathway:
- Activated in the absence of antibody, directly binding to the surface of infectious agents, such as bacterial endotoxins and fungal zymosan cell wall.
- Bypasses C1, C4, and C2, directly activating C3 through the properdin system, followed by the activation of C5 and the formation of the membrane attack complex (C5b6789).
Lectin Pathway:
- Initiated by mannan-binding lectin (MBL), produced by the liver, which binds to carbohydrate on pathogen surfaces.
- Activates C2 and C4, followed by the classical pathway.

Classical Pathway: Acquired immunity, initiated by antigen-antibody complex, and activates all components starting with C1.
Alternative Pathway: Innate immunity, initiated by microbial surface molecules, and bypasses C1, C4, and C2, starting with C3.
Lectin Pathway: Innate immunity, initiated by mannose residue on the surface of microorganisms, and activates all components except C1.

Cell Lysis: Occurs when the antigen is on the cell wall of bacteria or cells, such as RBCs, graft cells, or tumor cells, leading to the disruption of the cell membrane and lysis.
Opsonization: C3b acts as an opsonin, enhancing the phagocytosis of cells and antigen-antibody complexes.
Inflammatory Reactions:
- C3a is chemotactic, attracting neutrophils and macrophages to the site of inflammation.
- C3a, C4a, and C5a are anaphylatoxins, causing degranulation of mast cells and release of histamine and other inflammatory mediators, promoting the inflammatory reaction.