Complement component 5b

Complement Component 5b

Complement component 5b (C5b) is a crucial part of the complement system, which is an integral component of the innate immune system. The complement system enhances the ability of antibodies and phagocytic cells to clear pathogens from an organism. C5b plays a pivotal role in the formation of the membrane attack complex (MAC), which is essential for the lysis of pathogen cell membranes.

Structure and Formation

C5b is generated from the cleavage of complement component 5 (C5) by the enzyme C5 convertase. This cleavage results in two fragments: C5a, a potent anaphylatoxin, and C5b, which initiates the assembly of the MAC.

The formation of C5b occurs as follows:

• C5 is cleaved by C5 convertase into C5a and C5b.
• C5b rapidly associates with C6 to form the C5b6 complex.
• The C5b6 complex then binds to C7, forming the C5b67 complex, which inserts into the lipid bilayer of the target cell membrane.

Role in the Membrane Attack Complex

C5b is the first component of the terminal complement complex, also known as the membrane attack complex (MAC). The MAC is composed of C5b, C6, C7, C8, and multiple copies of C9. The steps in MAC formation are as follows:

1. C5b binds to C6, forming the C5b6 complex.
2. C5b6 binds to C7, forming C5b67, which inserts into the target cell membrane.
3. C8 binds to the C5b67 complex, anchoring it more firmly into the membrane.
4. Multiple C9 molecules polymerize around the C5b678 complex, forming a pore in the membrane.

The formation of this pore disrupts the cell membrane, leading to cell lysis and death of the target cell.

Biological Significance

The MAC is crucial for the defense against certain bacterial infections, particularly those caused by Neisseria species. Deficiencies in components of the MAC, including C5b, can lead to increased susceptibility to infections.

Clinical Implications

Deficiencies or dysfunctions in the complement system, including C5b, can result in a variety of clinical conditions. For example, individuals with deficiencies in the terminal complement components (C5-C9) are at increased risk for recurrent Neisseria infections.

Additionally, excessive activation of the complement system can contribute to inflammatory diseases. Therapeutic interventions targeting complement components, such as C5, are being explored for conditions like paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic uremic syndrome (aHUS).

See Also

• Complement system
• Membrane attack complex
• Anaphylatoxin