Complement is a central homeotic system of mammals and represents the first defense line of innate immunity. The human complement system is the first defense line of innate immunity aiming to maintain homeostasis by recognizing and removing damaged or modified self-material (e.g. apoptotic and necrotic cells and their fragments), as well as infectious foreign microbes.
Complement-related Infection
Complement activation may be initiated via one or more of three pathways: the classical, lectin, or alternative pathways. The regulatory network of complement is very intricate and accurate because there are a large number of zymogens, receptors and regulators participate in the enzymatic cascade cleavages. Excessive or insufficient activation will break the delicate balance between complement activation and inhibition, leading to various infection-related diseases, such as recurrent infection. There is conclusive evidence showed that septic shock, meningococcal meningitis, primary amebic meningoencephalitis, chemotherapy-induced neutropenia are associated with complement components.
When suffered from infectious diseases, individuals deficient in components are highly predisposed to the invasion, and often evolved into recurrent infections. Genome-wide analysis studies also point to a central role for complement in infectious disease pathogenesis. Physiological roles of complement in infectious diseases include:
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Defense Against Microbes
C3 is a crucial source of opsonins, which label bacteria for removal by phagocytes. always caused In severe recurrent infections, C3 deficiency is the most common causes, in addition, the proteins [C1, C4, mannose-binding lectin (MBL), MBL-associated serine protease 1 (MASP1) and MASP2] referred to classical pathway or lectin pathway are also associated with recurrent bacterial infections. Deficiencies of alternative pathway components or the positive regulator properdin predispose to gram-negative bacterial infections. Neisseria species, typically those causing meningococcal meningitis or sepsis is closely related with the terminal pathway-MAC deficiency.
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Protection Against Immune Complexes
Excessive immune complexes accumulation in capillary beds will trigger inflammation and tissue damage, while complement will block this unhindered aggregation. Classical pathway components C1 and fragments of C4 and C3 can mask antigens in the immune complex and disrupt the lattice, thereby limiting growth of the complex aggregates. When the receptors (CR1, CR3, and CR4) on phagocytic cells bind their ligands, immune complexes will be engulfed and destroyed.
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Priming Adaptive Immunity
Microbes coated with complement activation fragments provoke markedly greater antibody responses, for instance, C3a and C5a can enhance the activity of antigen-presenting cells (APCs) to present antigens and stimulate T cell proliferation. Researches revealed that CR2 on B cells can reduce the threshold for B cell receptor triggering and increase the amplitude of the response through a powerful costimulatory signal.
Fig.1 Complement during infection with a pathogen. (Merle, et al. 2015)
Complement provides numerous options for drug development as it is a proteolytic cascade that can collaborate with antibody-mediated immune response to provide defense against infection.
Creative Biolabs provides a series of therapeutic antibodies, inhibitors, soluble complement regulators, as well as customized services based on the complement-associated infection, including
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Recurrent infection
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Septic shock
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Meningococcal meningitis
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Primary amebic meningoencephalitis
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Chemotherapy-induced neutropenia
Our comprehensive complement platform offers a great number of complement-related products in a rapid and cost-effective manner. If you are interested, please feel free to contact us for more details.
Reference
1. Merle, N. S.; et al. (2015). Complement system part I–molecular mechanisms of activation and regulation. Frontiers in immunology. 6, 262.
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Questions & Answer
A: Complement therapeutics can help enhance the immune system's ability to clear bacterial infections. By targeting specific complement pathways, complement therapeutics can improve the body's defense mechanisms against bacteria.
A: Key complement components that are often targeted in complement therapeutics include C3, C5, Factor D, and Factor H. These component modulations can influence the downstream complement cascade. Complement inhibition involves blocking or regulating the activity of these complement proteins. In infections, this can be used to prevent excessive inflammation, tissue damage, and overactivation of the immune system.
A: Creative Biolabs designs complement therapies for specific pathogens based on how complement is activated and the unique characteristics of the pathogen. Our research is focused on developing novel complement inhibitors, improving vaccine strategies, and better understanding the role of the complement system in various infectious diseases.
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