Читать книгу Immunology - Richard Coico - Страница 92

The terminal components of the complement cascades—C5b, C6, C7, C8, and C9—are common to the three complement activation pathways. These components bind to one another and form a membrane attack complex (MAC) that results in the death (lysis) of the cell on which they deposit (Figure 4.4).

The first step in MAC formation is C6 binding to C5b on the cell surface. C7 then binds to C5b and C6, with C7 inserting into the outer membrane of the cell. The subsequent binding of C8 to C5b67 results in the complex penetrating deeper into the cell’s membrane. C5b‐C8 on the cell membrane acts as a receptor for C9, a perforin‐like molecule that binds to C8. Additional C9 molecules interact with the C9 molecule in the complex to form polymerized C9 (poly‐C9). Poly‐C9 forms a transmembrane channel that disturbs the cell’s osmotic equilibrium: ions pass through the channel and water enters the cell. The cell swells and the membrane becomes permeable to macromolecules, which then escape from the cell. The result is cell lysis.

Figure 4.4. Formation of membrane attack complex (MAC). Late‐stage complement components C5b–C9 bind sequentially to form a complex on the cell surface. Multiple C9 components bind to this complex and polymerize to form poly‐C9, creating a channel that disrupts the cell membrane.