Complement membrane attack complex

Complement membrane attack complex (MAC) is a structure typically formed on the surface of pathogen cells as a result of the activation of the complement system, a part of the immune system that enhances the ability of antibodies and phagocytic cells to clear microbes and damaged cells from an organism. The MAC is one of the final products of the complement system and is designed to disrupt the phospholipid bilayer of cells, leading to cell lysis and death.

Formation

The formation of the MAC begins with the cleavage of C5 into C5a and C5b by the C5-convertase. C5b binds to C6 to form a C5b-6 complex, which then binds to C7. This C5b-7 complex is able to insert into the phospholipid bilayer, where it acts as a receptor for a C8 molecule. The C5b-8 complex can then interact with C9 molecules to form the MAC. The MAC is a cylindrical structure that creates a pore in the membrane of the target cell, disrupting the cell's integrity and leading to cell lysis.

Function

The primary function of the MAC is to form a pore in the membrane of pathogenic cells, leading to cell lysis and death. This is a key mechanism by which the immune system can eliminate pathogenic cells. The MAC can also stimulate cells to release inflammatory cytokines, which can recruit additional immune cells to the site of infection.

Regulation

The formation and activity of the MAC is tightly regulated by several proteins, including CD59, which can prevent the incorporation of C9 into the MAC, and Clusterin and Vitronectin, which can inhibit the MAC at various stages of its formation.

Clinical significance

Defects in the formation or regulation of the MAC can lead to various diseases. For example, paroxysmal nocturnal hemoglobinuria is a disease characterized by the absence of CD59 on red blood cells, leading to increased lysis by the MAC. Conversely, some pathogens have evolved mechanisms to evade the MAC, contributing to their virulence.