Complement

Complement is a group of proteins that exist in human and animal body fluids and on the surface of cells. After activation, they are biologically active and can mediate immune and inflammatory responses. They are also called the complement system. The complement system consists of nearly 40 components, most of which are It is a glycoprotein, including: 13 kinds of intrinsic components, C1q, C1r, C1s, C2-C9, D factor and B factor; 10 kinds of regulatory proteins; 10 kinds of complement receptors, etc., discovered by Belgian doctor J.Bordet in 1890, In 1894, he further confirmed the existence of complement through bacterial antiserum experiments. Complement is not a single molecule, but a group of heat-labile, activated enzyme-active proteins that exist on the surface of serum, interstitial fluid and cell membranes, including more than 30 kinds of soluble proteins and membrane-bound proteins, so it is called the complement system. Complement is widely involved in the body's microbial defense response and immune regulation, and can also mediate the damage response of immune pathology. It is an effector system and effect amplification system with important biological functions in the body. Complement is a normal serum component and has nothing to do with antigenic stimulation.

Understanding the Complement System

Due to the advancement of protein chemistry and immunochemistry techniques, the successful separation and purification of complement components from blood has proved that the argument that complement is a single component is incorrect, and it is composed of three groups of globulin macromolecules. That is, the first component is composed of 9 complement components, which are respectively named C1, C2, C3, C4, C5, C6, C7, C8, and C9. Among them, C1 is composed of three subunits, named C1q, C1r, and C1s, so the first component is composed of 11 globulin macromolecules. Some new serum factors were found to be involved in complement activation, but they were not activated via antigen-antibody complexes. Rather, through the bypass activation pathway. These factors include factor B, factor D, which constitute the second component of complement. Later, a variety of inhibitory or inactivating factors involved in the control of complement activation were found, such as C1 inhibitors, I factors, H factors, C4 binding proteins, and anaphylatoxin inactivating factors. These factors can control the activation of complement molecules and play a regulatory role in maintaining the balance of complement in the body. They constitute the third component of complement.

Due to the in-depth study of another pathway of complement activation, there is a new recognition of the biological significance of the complement system, which breaks the traditional view of complement and establishes a new concept. That is, the complement system is a multi-molecular system composed of nearly 20 kinds of serum proteins, which has enzyme activity and self-regulation. It has at least two different activation pathways, and its biological significance is not only an auxiliary or enhancer factor of antibody molecules, but also has an independent biological role, playing an important role in the defense function of the body, the regulation of the immune system function and the immunopathological process. effect.

In 1968, the Complement Nomenclature Committee of the World Health Organization (WHO) gave a unified name to complement. Named after C1-C9 respectively, some newly discovered components and factors were also named uniformly in 1981. The peptide chain structure of each complement is represented by Greek letters, such as C3α and β chains. The enzymatic fragments of each molecule can be represented by lowercase English letters, such as C3a and C3b and other enzymatic fragments, and molecules with enzymatic activity can be represented by drawing a horizontal line on them. For example, C1 is a molecule without enzymatic activity, while C1 is a molecule with enzymatic activity. . The complex with enzymatic activity should be represented by its fragments, such as C3 convertase can be represented by C4b2b.

Complement molecules are produced by various cells such as liver cells, macrophages, and intestinal mucosal epithelial cells. Its physical and chemical properties and its content in serum vary greatly. The chemical composition of all complement molecules is polysaccharide protein, and the molecular weight of each complement component varies widely. Among them, the molecular weight of C4-binding protein is the largest at 550,000, and the molecular weight of factor D is the smallest at 23,000. The electrophoretic mobility of most complement components belongs to beta globulin, and a few belong to a globulin and gamma globulin. Complement proteins in serum account for about 10% of the total globulins, of which the highest content is C3, which contains about 1 mg/ml, while D factor only contains 1 μg/ml, the difference between the two is about a thousand times. In some human diseases, the total complement content or single component content may change, so the determination of the complement level in body fluids or the observation of complement localization in tissues has certain significance for the diagnosis of some diseases.

Research area of Complement field

Complement is an important component of the immune system, and its research areas cover many scientific fields. The following are several major areas of complement research:

1. Immunology: The complement system is an important part of the body's natural and adaptive immunity. Researchers are working to uncover the mechanisms of complement in the immune response, including identifying and clearing pathogens, modulating inflammatory responses, and stimulating immune cells. Studying the function and regulation of complement helps to understand the normal function of the immune system and the pathogenesis of abnormal immune diseases.
2. Inflammation and autoimmune diseases: The complement system plays an important role in inflammatory responses and autoimmune diseases. Researchers explore the role of complement in the regulation of inflammation, including the production and regulation of inflammatory mediators, the activation and regulation of inflammatory cells, etc. In addition, the study of the relationship between complement and autoimmune diseases (such as systemic lupus erythematosus, rheumatoid arthritis, etc.) will help reveal the mechanism of disease and develop new treatment strategies.
3. Infection pathogens and immune escape: the complement system is involved in the removal of infection pathogens such as bacteria, viruses and fungi. Researchers are committed to studying the interaction between complement and various pathogens, revealing how pathogens use different mechanisms to evade or manipulate the complement system, so as to provide clues to guide the prevention and treatment of infectious diseases.
4. Antibody-dependent cellular cytotoxicity (ADCC): ADCC is the mechanism by which immune cells kill target cells by recognizing antigens labeled with antibodies on the surface of target cells and releasing cytotoxins. Complement plays an important role in ADCC, promoting the activation of immune cells and the lysis of target cells. Studying the role of complement in ADCC will help in the development of immunotherapeutic strategies against cancer and infectious diseases.
5. Complement and nervous system: In recent years, studies have found that the complement system plays an important role in neural development, synapse repair and neurodegenerative diseases. Researchers are dedicated to studying the function and regulation of complement in the nervous system, including neuronal development and connectivity, synaptic plasticity, and neuroinflammation. These studies contribute to a deep understanding of the pathogenesis of neurological diseases and provide new ideas for the development of related treatments.

Clinical Significance of Complement

Complement has extensive clinical significance and plays an important role in the diagnosis, treatment and prevention of many diseases. The following are several important significances of complement in clinical practice:

1. Diagnosis and monitoring of immune diseases: The determination of complement can be used as an auxiliary diagnostic marker for some immune diseases. For example, a decrease in complement is associated with autoimmune diseases (such as systemic lupus erythematosus, rheumatoid arthritis, etc.). Determination of complement levels can be used to assess disease activity, monitor the effect of treatment, and predict prognosis.
2. Diagnosis and treatment of infectious diseases: Complement plays an important role in fighting against infectious pathogens such as bacteria, viruses and fungi. In the diagnosis of certain infectious diseases, complement activity and levels can provide information about the extent of infection and exposure to the pathogen. In addition, detection of complement activity can also guide therapeutic strategies, such as considering pathogen escape mechanisms from the complement system when selecting antibiotic regimens.
3. Monitoring and prediction of tumor therapy: Complement has potential in immune monitoring and prediction of tumors. Some tumor cells may express markers of complement activation on the surface, such as deposition of complement fixation protein (C3b). Detection of these markers can be used to monitor tumor growth and spread and predict tumor response to immunotherapy.
4. Treatment of complement-related diseases: Certain diseases are related to abnormal function or overactivation of the complement system. For example, treatment of complement-related disorders such as idiopathic membranous nephropathy and relapsing cold hemoglobinuria may include controlling complement activation, suppressing inflammatory responses, and protecting damaged tissues.
5. Development of immunomodulatory and therapeutic strategies: In-depth research on the complement system helps to develop new immunomodulatory and therapeutic strategies. For example, researchers are exploring the use of antibodies or protein molecules to modulate the activity of the complement system to improve clinical outcomes in autoimmune diseases, infectious diseases and cancer treatment, among others.

Summary of Complement

All in all, complement plays an important role in the immune system, with the functions of promoting inflammatory response, bacteriolysis, garbage cell removal and immune regulation. In-depth research on complement will help reveal the working principle of the immune system and the development mechanism of diseases, and provide new ideas and methods for the treatment and prevention of diseases.

Complement Components and Factors