Complement proteins

Complement proteins are a group of proteins that play a crucial role in the immune system's ability to fight off pathogens and clear damaged cells from an organism. They are part of the innate immune system, which serves as the first line of defense against infections. Complement proteins work by enhancing (complementing) the ability of antibodies and phagocytic cells to clear microbes and damaged cells from an organism, promote inflammation, and attack the pathogen's cell membrane.

Overview

The complement system consists of a series of small proteins found in the blood plasma and on cell membranes, which are synthesized mainly by the liver. These proteins are normally inactive but can be activated sequentially in a cascade-like manner. The activation pathways of the complement system include the classical pathway, which is triggered by antibody-antigen complexes; the lectin pathway, which is initiated by mannose-binding lectin binding to specific sugars on the surface of microbes; and the alternative pathway, which can be activated on microbial surfaces in the absence of antibodies.

Once activated, the complement system leads to a series of reactions that help to fight infections, including:

• Opsonization - marking pathogens for destruction by phagocytes
• Chemotaxis - attracting macrophages and neutrophils
• Cell lysis - rupturing the membranes of foreign cells
• Agglutination - clumping together of pathogens
• Enhancement of the inflammatory response

Components

The complement system is composed of over 30 proteins and protein fragments, including serum proteins, serine proteases, and receptors. The key components are numbered C1 through C9, and their activation is tightly regulated by various regulatory proteins to prevent damage to host cells.

C1-C9 Components

• C1 - Initiates the classical pathway
• C2 and C3 - Play a central role in the activation of the complement system
• C4 - Part of the classical and lectin pathways
• C5-C9 - Form the membrane attack complex (MAC) that leads to cell lysis

Regulation

The activity of complement proteins is regulated by several control proteins to ensure that the complement system is directed against pathogens and does not damage host tissues. These regulatory proteins include Factor H and Factor I, which inhibit the alternative pathway, and C1 inhibitor, which controls the activation of the classical pathway.

Clinical Significance

Dysregulation or genetic deficiencies in complement proteins can lead to increased susceptibility to infections, autoimmune diseases, and other immune-related disorders. For example, deficiencies in early components of the classical pathway (C1, C2, C4) are associated with autoimmune diseases like Systemic Lupus Erythematosus (SLE). On the other hand, deficiencies in components of the membrane attack complex (C5-C9) can lead to recurrent infections with Neisseria bacteria.

Therapeutic interventions targeting the complement system are being developed for a variety of diseases, including age-related macular degeneration, rheumatoid arthritis, and sepsis.

See Also

• Immune system
• Inflammation
• Antibody
• Phagocytosis