C3b

Complement pathway

C3b is a fragment of the complement component 3 (C3) protein, which plays a crucial role in the immune system's complement system. The complement system is a part of the innate immune system, responsible for enhancing the ability of antibodies and phagocytic cells to clear pathogens and damaged cells from an organism, promote inflammation, and attack the pathogen's cell membrane. C3b is generated from the cleavage of C3 by convertase enzymes in the complement cascade. This process is essential for the complement system's activation and function, serving as a pivotal step in the opsonization of pathogens, which marks them for destruction by phagocytes, and in the formation of the membrane attack complex (MAC) that can directly lyse pathogen cells.

Function

C3b functions primarily through its ability to opsonize pathogens and damaged cells. Opsonization is the process by which pathogens are marked for ingestion and destruction by phagocytes. Once C3 is cleaved into C3b, the C3b molecule can bind covalently to the surface of pathogens. This binding enhances the ability of phagocytic cells, such as macrophages and neutrophils, to recognize, engulf, and destroy the opsonized pathogens in a process known as phagocytosis.

Furthermore, C3b plays a critical role in the amplification of the complement cascade. It participates in the formation of the C3 and C5 convertases, which are enzyme complexes that cleave C3 and C5, respectively, amplifying the cascade's response. The cleavage of C5 leads to the formation of the C5b-9 complex, also known as the membrane attack complex (MAC), which creates pores in the membrane of target cells, leading to their lysis.

Regulation

The activity of C3b is tightly regulated by several regulatory proteins to prevent damage to host cells. These proteins include Factor H and Factor I, which inactivate C3b to iC3b, preventing the formation of the C3 convertase and thus inhibiting the complement cascade. This regulation is crucial to avoid excessive inflammation and damage to host tissues.

Clinical Significance

Alterations in the regulation or function of C3b can lead to various immune disorders. For example, deficiencies in C3b or its regulatory proteins can result in increased susceptibility to infections, as the opsonization and clearance of pathogens are impaired. Conversely, uncontrolled activation of C3b can contribute to autoimmune diseases, where the immune system attacks the body's own cells and tissues, due to the excessive inflammation and tissue damage caused by inappropriate complement activation.

Genetic and Molecular Aspects

The gene encoding the C3 protein is located on chromosome 19 in humans. Mutations in this gene can affect the production, structure, and function of C3 and its fragments, including C3b, leading to complement system-related disorders.