Complement C3/C4 (C3/C4)

Complement is a serum protein found in human and vertebrate serum and tissue fluids that is heat-insensitive, enzymatically active when activated, and mediates immune responses and inflammatory reactions. It can be activated by antigen-antibody complexes or microorganisms, leading to lysis or phagocytosis of pathogenic microorganisms. Can be activated by three separate and intersecting pathways, the classical pathway, the bypass pathway, and the lectin pathway. Complement C3 and complement C4 are more abundant in serum than other complement molecules, and both have very important roles in accomplishing multiple functions of the complement system.

Complement 3 (C3), a β₂-globulin synthesized by the liver, consists of two polypeptide chains, α and β. C3 is the most abundant complement component in serum, and is cleaved into two fragments, C3a and C3b, by C3 converting enzyme, which play important roles in both the classical and bypass activation pathways of complement.

Complement 4 (C4) is a multifunctional β1-globulin that is present in plasma. In complement traditional pathway activation, C4 is hydrolyzed by C1s to C4a and C4b, which play roles in complement activation, promotion of phagocytosis, prevention of immune complex deposition, and neutralization of viruses.

KMD Bioscience is a company dedicated to providing high-quality biologically active raw materials such as antigens, antibodies, enzymes and substrates, as well as related technical services. KMD Bioscience has a series of technical platforms for protein recombination, antibody production, purification and diagnostic reagent R&D and production (including immunochromatography, enzyme immunoassay and chemiluminescence); and a group of highly qualified in vitro diagnostic upstream and downstream technicians with rich experience, which provide guarantee for the company's research and development, and production of high-quality raw materials for in vitro diagnostic reagents and related technologies.

Activation of complement system

The activating pathway of complements, also known as the complement system. The components of the complement are activated by the antigen-antibody complex and other components, ions, etc., which cause immune cytolysis and immune haemolysis, i.e., the lysis of cells, bacteria, red blood cells, etc., or immune adhesion and many other immunobiological phenomena. The complement system can be activated through three (classical pathway, bypass pathway, and lectin pathway) relatively independent and interrelated pathways, thus exerting a variety of biological effects such as regulating phagocytosis, lysing cells, mediating inflammation, immunomodulation, and clearing immune complexes, including enhancing phagocytosis and phagocytosis chemotaxis, increasing vascular permeability, neutralizing viruses, cytolysis, and regulating immune responses. regulation of immune response, etc.

Figure 1 Schematic structure of C3 molecule

Figure 2 Schematic diagram of C4A molecular structure

Composition of the complement system

Most of the complement components are synthesized by the liver, and a few are produced by macrophages, etc. Most of the complement components in serum are synthesized by the liver. Most of the complement components in serum are secreted by hepatocytes, but in the inflammatory zone macrophages are the main source of complement. Its composition is categorized according to its biological function into complement intrinsic components, complement regulatory proteins, and complement receptors. The intrinsic components of the complement system are those necessary to participate in the three activation pathways of complement; complement regulatory proteins are present in body fluids or on the surface of cell membranes capable of regulating complement activity. Including: soluble regulatory proteins (present in body fluids), membrane-bound regulatory proteins (present on cell membranes); complement receptors present on the surface of cell membranes, can bind to complement active fragments or regulatory proteins, mediating a variety of biological effects of complement components.

Physiological functions of complement

Ⅰ. Cytotoxic effects

1. Complement system activation → Membrane attack complex → Lysis of target cells

① Anti-infection dissolve bacteria, viruses, parasites; ② Anti-tumor involved in the body's anti-tumor immune effect mechanism; ③ Pathological conditions cause the body's own cell destruction

Ⅱ. regulating phagocytosis

C3b, C4b and iC3b and pathogenic microorganisms and other non-specific binding, through the phagocyte surface CR1 and CR3 binding and promote phagocyte phagocytosis of pathogens, known as complement-mediated conditioning.

Ⅲ. Inflammation-mediated effects

1. Allergic toxin effect: C3a, C4a, C5a can lead to acute inflammatory response.

Among them, the effect of C5a is the strongest, about 20 times the effect of C3a, C4a has the weakest effect.

2. Chemokine: C5a is a chemokine for neutrophils and monocytes-macrophages, which can attract phagocytes to the lesion site, and enhance their phagocytosis and killing activity against pathogens.

3. Kinin-like effect: C2b has kinin-like effect, which can make small blood vessels dilate, increase permeability and cause inflammatory congestion and edema.

Ⅳ. Removal of immune complexes

Including immune adhesion and inhibition of immune complex formation.

V. Participate in adaptive immune response

1. Conditioning action promotes antigen uptake and presentation, initiating adaptive immune response.2. C3d binds to antigen, which can cross-link BCR with co-receptors, initiating the first signal of B cell activation.3. 3b binds to B cell CR1, promoting B cell proliferation and differentiation.4. CR1 and CR2 on the surface of FDC can retain IC in the germinal centers, inducing and maintaining Bm cells.5. Through cytotoxic effect, conditioning effect and clearance, etc. involved in the effector phase of immune response.

KMD Bioscience offers a variety of diagnostic components for infectious diseases, tumors, inflammation, nail function, hormones, and other areas.

KMD Bioscience can provide a wide range of bioactive materials and technical services for IVD, which are widely used by domestic and foreign manufacturers of related reagents. These include, but are not limited to, customized development of antigens and antibodies, antigen-antibody labeling and coupling, antibody pair screening and purification, immunochromatography, enzyme immunoassay and chemiluminescence system optimization and process debugging, and many other technologies.