Complement component 9

Complement component 9 (C9) is a protein that plays a crucial role in the immune system, specifically in the complement system, which is a part of the innate immune response. C9 is involved in the formation of the membrane attack complex (MAC), a structure that creates pores in the membranes of target cells, leading to their lysis and death. This process is a defense mechanism against pathogens such as bacteria and viruses.

Structure and Function

C9 is a glycoprotein composed of a single polypeptide chain. It is the last component to join the membrane attack complex. The activation of C9 is tightly regulated, requiring the prior assembly of the C5b-8 complex. Once C5b, C6, C7, and C8 have formed a complex on the surface of a target cell, multiple C9 molecules polymerize to form a tubular structure that inserts into the cell membrane, creating a pore. This pore disrupts the integrity of the cell membrane, leading to cell death.

Activation and Regulation

The activation of C9 is part of the terminal pathway of the complement system, which can be initiated through three main pathways: the classical pathway, the lectin pathway, and the alternative pathway. All three pathways converge at the activation of C3, leading to the formation of C5 convertase, which cleaves C5 into C5a and C5b. C5b then initiates the assembly of the terminal complement complex (C5b-9), including C9.

Regulation of C9 and the MAC is crucial to prevent damage to host cells. Proteins such as CD59 (protectin) inhibit the formation of the MAC by preventing the recruitment of C9 to the C5b-8 complex on host cells.

Clinical Significance

Alterations in the function or regulation of C9 can lead to various diseases. Deficiency in C9 is rare but can increase susceptibility to certain bacterial infections, particularly Neisseria meningitidis, due to the reduced efficiency of the membrane attack complex. Conversely, uncontrolled activation of the complement system, including excessive formation of the MAC, can contribute to tissue damage in autoimmune diseases, such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA).

Genetic Aspects

The gene encoding C9 is located on chromosome 5 in humans. Genetic variations in this gene can affect the expression and function of C9, potentially impacting the individual's immune response.

Research and Therapeutics

Research into C9 and the complement system has led to the development of therapeutic interventions targeting various components of the complement pathway. Inhibitors of C9 and the MAC are being explored as potential treatments for diseases characterized by excessive complement activation.

See Also

• Complement system
• Membrane attack complex
• Innate immune system
• Autoimmune diseases