Complement

System of hepatically synthesized plasma proteins that play a role in innate immunity and inflammation. Membrane attack complex (MAC) defends against gram ⊖ bacteria. The CH₅₀ test is used to screen for activation of the classical complement pathway.

Activation Pathways

• Classic—IgG or IgM mediated.
• Alternative—microbe surface molecules.
• Lectin—mannose or other sugars on microbe surface.

Mnemonic: General Motors makes classic cars (for Classic pathway).

Functions

• C3b—opsonization.
• C3a, C4a, C5a—anaphylaxis.
• C5a—neutrophil chemotaxis.
• C5b-9 (MAC)—cytolysis.

Specific Functions and Inhibitors

• C3b binds to lipopolysaccharides on bacteria.
• MAC complex is important for neutralizing Neisseria species. Deficiency results in recurrent infection.

Mnemonic: Get “Neis” (nice) Big MACs from 5-9 pm.

Opsonins—C3b and IgG are the two primary opsonins in bacterial defense; they enhance phagocytosis. C3b also helps clear immune complexes.

Inhibitors—Decay-accelerating factor (DAF, also called CD55) and C1 esterase inhibitor help prevent complement activation on self cells (e.g., red blood cells).

Complement Activation Pathways Diagram

#boundingbox

This diagram illustrates the three main complement activation pathways: the Alternative, Lectin, and Classic pathways, and how they converge to activate the complement cascade.

The Classic Complement Pathway

#boundingbox

The Classic pathway is initiated by antigen-antibody complexes, specifically C1, which then activates C2 and C4, forming the C4b2b complex, a C3 convertase. This convertase cleaves C3 into C3a and C3b.

The Lectin Complement Pathway

#boundingbox

The Lectin pathway is initiated by microbial surfaces, such as mannose, leading to the formation of a C3-like complex and subsequently the C4b2b C3 convertase, similar to the Classic pathway.

The Alternative Complement Pathway

#boundingbox

The Alternative pathway is initiated by spontaneous and microbial surfaces, leading to the formation of the C3bBb C3 convertase, which amplifies C3b generation.

Convergence and Membrane Attack Complex (MAC) Formation

#boundingbox

All three pathways converge at the cleavage of C3 into C3a and C3b. C3b then participates in forming C5 convertase, which cleaves C5 into C5a and C5b. C5b then initiates the formation of the Membrane Attack Complex (MAC), C5b-9, leading to cell lysis and cytotoxicity.

Topics Covered:

• Introduction to Complement System
• Complement Activation Pathways
• Functions of Complement Components (Part 1)
• Functions of Complement Components (Part 2) & Inhibitors
• Overview of Complement Pathways Diagram
• Detail of Classic Pathway
• Detail of Lectin Pathway
• Detail of Alternative Pathway
• Convergence and MAC Formation