C1 complex

C1 complex is a large, multimolecular entity that plays a crucial role in the classical pathway of the complement system, which is a part of the immune system responsible for enhancing the ability of antibodies and phagocytic cells to clear pathogens from an organism. The C1 complex is the first component of the classical pathway and is essential for its activation, leading to a cascade of reactions that promote inflammation, opsonization, and cell lysis.

Composition

The C1 complex is composed of three types of molecules: C1q, C1r, and C1s. C1q is a protein with a unique structure that allows it to bind to the Fc region of antibodies that are themselves bound to antigens, effectively recognizing the presence of pathogens. Once C1q is bound to an antibody, it activates C1r, which is a serine protease. Activated C1r then cleaves and activates C1s, another serine protease. The active C1s cleaves the next components in the complement cascade, C4 and C2, marking the initiation of the classical pathway.

Activation

Activation of the C1 complex is initiated when C1q binds to the Fc region of antibodies (mainly IgM or IgG) that are attached to antigens on the surface of a pathogen. This interaction induces a conformational change in C1q, which triggers the autoactivation of C1r. Activated C1r then cleaves and activates C1s, setting off the cascade of reactions in the classical complement pathway.

Function

The primary function of the C1 complex is to initiate the classical pathway of the complement system upon recognition of foreign pathogens. This leads to a series of reactions that result in the opsonization of pathogens, making them more easily phagocytosed by macrophages and other cells; the recruitment of inflammatory cells to the site of infection; and the formation of the membrane attack complex (MAC), which can directly lyse pathogen cells.

Regulation

The activity of the C1 complex is tightly regulated to prevent unnecessary activation and damage to host tissues. C1 inhibitor (C1-INH) is a key regulatory protein that binds to activated C1r and C1s, inhibiting their protease activity and preventing the further progression of the complement cascade. Deficiencies in C1-INH can lead to uncontrolled activation of the complement system and are associated with diseases such as hereditary angioedema.

Clinical Significance

Alterations in the function or regulation of the C1 complex can lead to various diseases. For example, deficiencies in components of the C1 complex can result in immune deficiencies, where the body is unable to effectively clear certain pathogens. On the other hand, excessive or uncontrolled activation of the C1 complex can contribute to autoimmune diseases, where the complement system attacks the body's own tissues.