The immune system relies on a variety of defense mechanisms to protect the body from invading pathogens and damaged cells. One such mechanism is the complement system, an integral part of the innate immune response. This system consists of numerous proteins that work together to enhance the body’s ability to clear microbes and cellular debris. The membrane attack stage represents a powerful final step within this cascade, leading to the direct elimination of threats.
Building Blocks of the Membrane Attack Complex
The Membrane Attack Complex (MAC) is a multiprotein structure assembled from a specific sequence of complement proteins. It includes C5b, C6, C7, C8, and multiple units of C9.
C5b is a fragment derived from the complement protein C5, which initiates the MAC assembly. C6 and C7 are soluble proteins that associate with C5b to stabilize the initial complex and facilitate its interaction with cell membranes. C8 is another protein composed of three chains (alpha, beta, and gamma) that binds to the developing complex, further anchoring it to the target cell’s lipid bilayer. Finally, C9 molecules are recruited in multiple copies, ranging from 10 to 18 units, to complete the MAC structure.
How the Membrane Attack Complex Assembles
The formation of the Membrane Attack Complex begins with the proteolytic cleavage of complement protein C5 into C5a and C5b by an enzyme called C5 convertase. This C5b fragment then binds to C6, forming a C5b-6 complex. C7 joins this complex, creating C5b-6-7.
The C5b-6-7 complex undergoes a conformational change that exposes a hydrophobic region on C7, allowing it to insert into the phospholipid bilayer of the target cell membrane. C8 binds to the membrane-associated C5b-6-7 complex, forming C5b-6-7-8. This C5b-8 complex serves as a nucleation site for the recruitment and assembly of C9 molecules. Multiple C9 molecules then bind to the C5b-8 complex, arranging themselves into a ring-like structure that spans the membrane.
How the Membrane Attack Complex Damages Cells
Once assembled, the Membrane Attack Complex forms a pore in the target cell’s membrane. This transmembrane pore, approximately 10 nanometers in diameter, disrupts the cell’s membrane integrity. The pore allows for the uncontrolled passage of molecules across the membrane.
The pore leads to a rapid influx of water and ions into the cell, driven by osmotic gradients. This uncontrolled movement causes the cell to swell. As the cell takes on water, its internal pressure increases until the membrane can no longer withstand the strain, leading to cell lysis, or bursting, and cell death.
The Membrane Attack Complex in Action
The Membrane Attack Complex plays a significant role in the body’s immune defense by eliminating threats. It is effective against Gram-negative bacteria, due to its membrane-lysing action. The MAC’s ability to create pores in cell membranes targets these pathogens.
Beyond bacteria, the MAC also clears virus-infected cells and eukaryotic parasites. The body has mechanisms to prevent MAC formation on healthy host cells, ensuring its targeted action against foreign or compromised cells. This targeting highlights the MAC’s role as a direct effector in the innate immune response.