Membrane attack complex

The Membrane Attack Complex (MAC) is a structure formed on the cell membranes of bacteria and other pathogens that leads to cell lysis and death. It is part of the immune system's defense mechanism, specifically the complement system, which is a component of the innate immune system. The MAC is the final product of the complement cascade, which is initiated to help defend against microbial infections.

Structure and Formation

The MAC is composed of several complement proteins, including C5b, C6, C7, C8, and multiple copies of C9. The formation of the MAC begins when the complement protein C5 convertase cleaves C5 into C5a and C5b. C5b then binds to C6 and C7, which insert into the cell membrane. C8 joins and anchors the complex more firmly into the membrane. Finally, C9 molecules polymerize and form a pore in the membrane, known as the MAC pore.

Function

The primary function of the MAC is to disrupt the phospholipid bilayer of target cells, leading to cell lysis and death. This is crucial in the body's defense against pathogens, particularly bacteria and virus-infected cells. By forming pores in the membranes of these cells, the MAC causes an influx of water and ions, leading to osmotic swelling and eventual cell rupture.

Clinical Significance

Abnormal regulation of MAC formation can lead to tissue damage and is implicated in various diseases. For example, excessive or uncontrolled MAC formation is a factor in some types of autoimmune diseases and inflammatory conditions. Conversely, insufficient MAC activity can lead to increased susceptibility to infections.

Regulation

The activity of the MAC is regulated by several proteins to prevent damage to host cells. Proteins such as CD59 and protectin inhibit the formation of the MAC by preventing the recruitment of C9, thus protecting host cells from unintended complement activation and damage.

Research and Therapeutics

Research into the MAC has led to the development of therapeutic interventions that modulate the activity of the complement system. These therapies are aimed at treating diseases caused by excessive complement activation, such as atypical hemolytic uremic syndrome (aHUS) and paroxysmal nocturnal hemoglobinuria (PNH).