Complement System

Creative BioMart Complement System Product List

Complement System Background

About Complement System

The complement system is an intricate and essential component of the immune system, playing a vital role in host defense against pathogens, immune regulation, and tissue homeostasis. It is a complex cascade of proteins that acts in a coordinated manner to recognize, opsonize (mark for destruction), and eliminate foreign invaders, such as bacteria, viruses, and other microorganisms. Additionally, the complement system contributes to the clearance of immune complexes, apoptotic cells, and damaged tissues.

The complement system can be activated through three main pathways: the classical pathway, the lectin pathway, and the alternative pathway.

1. Classical Pathway: The classical pathway is primarily triggered by the binding of specific antibodies, such as immunoglobulin G (IgG) or immunoglobulin M (IgM), to target antigens on the surface of pathogens. This binding activates complement proteins, including C1q, C1r, and C1s, forming the C1 complex. The subsequent activation cascade involves the cleavage of C4 and C2, leading to the formation of C3 convertase (C4b2a). C3 convertase cleaves C3 into C3a and C3b, initiating downstream complement activation.
2. Lectin Pathway: The lectin pathway is initiated when pattern recognition molecules, known as mannose-binding lectins (MBLs), or ficolins, bind to specific sugar patterns on the surface of pathogens. This binding activates associated serine proteases (MASPs), leading to the cleavage of C4 and C2 to form C3 convertase. The lectin pathway serves as an early recognition and activation mechanism independent of antibody involvement.
3. Alternative Pathway: The alternative pathway represents a continuous low-level activation process that continuously surveys the body for any foreign substances. It is initiated by the spontaneous hydrolysis of C3, resulting in the formation of C3b. Properdin, a regulatory protein, stabilizes C3b and allows the formation of C3 convertase (C3bBb). This convertase amplifies the complement cascade by generating more C3b, leading to the opsonization of pathogens and the assembly of the membrane attack complex (MAC).

The activation of any of these pathways results in the generation of C3 and C5 convertases, which cleave C3 and C5, respectively. These cleavage events trigger a series of downstream reactions, including the opsonization of pathogens by C3b, the recruitment of immune cells (chemotaxis) through the release of anaphylatoxins (C3a, C4a, C5a), and the assembly of the MAC (C5b-9) that forms pores in the membranes of target cells, leading to their lysis and destruction.

Importantly, the complement system is tightly regulated by numerous complement regulatory proteins to prevent excessive activation and potential damage to host cells. These regulatory proteins include factors such as factor H, factor I, and membrane-bound regulators like CD55 and CD59.

In summary, the complement system is a complex network of proteins that plays a critical role in innate immunity. It recognizes and eliminates pathogens, facilitates immune responses, and maintains tissue homeostasis. The complement system's activation and regulation are tightly controlled to ensure an effective immune response while minimizing self-damage.

Fig.1 Schematic overview of complement system. (Franzin R, et al., 2021)

Major Functions of Complements

Some major functions of complements are:

1. Cell lysis: Membrane attack complex formed by C5b6789 components ruptures the microbial cell surface which kills the cell.
2. Opsonization and Phagocytosis: C3b, bound to the immune complex or coated on the surface of a pathogen, activates phagocytic cells. These proteins bind to specific receptors on the phagocytic cells to get engulfed.
3. Chemotaxis: Complement fragments attract neutrophils and macrophages to the area where the antigen is present. These cell surfaces have receptors for complements, like C5a, and C3a, thus, running towards the site of inflammation, i.e. chemotaxis.
4. Activation of Mast Cells and Basophils and Enhancement of Inflammation: The proteolytic complement fragments, C5a, C4a, and C3a induce acute inflammation by activating mast cells and neutrophils. All three peptides bind to mast cells and induce degranulation, with the release of vasoactive mediators such as histamine. These peptides are also called anaphylatoxins because the mast cell reactions they trigger are characteristic of anaphylaxis. Binding to specific complement receptors on cells of the immune system, they trigger specific cell functions, inflammation, and secretion of immunoregulatory molecules.
5. Production of Antibodies: B cells have receptors for C3b. When C3b binds to B-cell, it secretes more antibodies. Thus C3b is also an antibody-producing amplifier that converts it into an effective defense mechanism to destroy invading microorganisms.
6. Immune Clearance: The complement system removes immune complexes from the circulation and deposits them in the spleen and liver. Thus it acts as an anti-inflammatory function. Complement proteins promote the solubilization of these complexes and their clearance by phagocytes.

Available Resources for Complement System

• At Creative BioMart, we offer a wide range of products related to the complement system, including recombinant proteins, and others. Our services are customizable to cater to the specific needs of researchers in academia and the biopharmaceutical industry.
• In addition to our products and services, we provide a wealth of resources covering various aspects of the complement system. These resources encompass involved pathways, protein functions, interacting proteins, articles, research areas, and other relevant topics.
• Creative BioMart is committed to supporting your research and development endeavors in the field of the complement system. We encourage you to explore our product offerings, take advantage of our tailored services, and utilize our comprehensive resources to advance your scientific pursuits.

If you have any questions, requirements, or cooperation intentions, please feel free to contact us. We very much look forward to working with you and helping you achieve research and commercial success.

Reference:

1. Franzin R, Stasi A, Fiorentino M, et al. Inflammaging and Complement System: A Link Between Acute Kidney Injury and Chronic Graft Damage [published correction appears in Front Immunol. 2021 Jan 08;11:630855]. Front Immunol. 2020;11:734.