Inflammation and immunology
C. Simon Herrington in Muir's Textbook of Pathology, 2020
The complement system consists of more than 20 components circulating within the plasma (Figure 4.3). It is a major defence mechanism, critical in the initiation of acute inflammation. There are three pathways for the activation of complement: the classical, mannose-binding lectin (MBL), and alternative pathways of complement activation. The classical pathway of complement activation is dependent on antibody−antigen complex activation of complement component C1 and thus will be described further in the adaptive immunity section. The MBL pathway is dependent on the MBL component of the complement pathway. MBL is activated on binding to certain polysaccharides such as mannose, which do not exist in the extracellular spaces of a healthy body but are produced in large quantities by certain bacteria. Therefore, MBL can be regarded as a soluble PRR. Finally, the alternative pathway of complement activation occurs when complement component C3 spontaneously hydrolyses into C3a and C3b. C3b can then mediate further amplify complement activation by all three pathways and is required for activation of all later complement components. C3b binds to any nearby plasma membranes, which will usually be the body's own cells, which contain multiple pathways of complement control, preventing further complement activation. Bacterial cells lack these complement control components, allowing further complement activation.
Immunology of lung transplantation
Wickii T. Vigneswaran, Edward R. Garrity, John A. Odell in LUNG Transplantation, 2016
The complement system consists of three major pathways referred to as classical, lectin, and alternative. Constituents of the system include a complex array of proteins that are divided into circulating complement produced by the liver and localized complement components produced by cells migrating to or present in tissues.35 Complement activation results in phagocytic removal or cellular lysis by membrane attack complex formation, as well as in the generation of inflammatory mediators.36 The most critical components involved in this process are C3 and C5 and their cleavage products. The action of activated complement proteins is subsequently regulated by complement regulatory proteins, including CD55 (also known as decay-accelerating factor [DAF]) and CD46.37,38
Specific Host Restance: The Effector Mechanisms
Julius P. Kreier in Infection, Resistance, and Immunity, 2022
The complement components, designated by a capital C, are all proteins. They comprise ten percent of total human serum protein. Each component is identified by a numbered suffix, C1, C2, etc., that reflects the order in which they were originally purified rather than the order in which they react. Additional serum proteins called factors B, D, and P (properdin) are also involved in complement activation. The complement components circulate in the blood in inactive form. During the activation process, they may change in conformation, undergo proteolytic cleavage, or aggregate into multisubunit proteins. By convention, when a complement protein is split in two, the fragments are designated by a lower case a (for the smaller piece) and b (for the larger piece). The activation mechanisms can generate a protein with an enzymatic site or a binding site not exposed on the inactive component. The sites generated enable each component to react with the next component in the cascade. Activated complement proteins have biological activities that play a variety of roles in eliminating the invading microbe. In the classical pathway, factors B and D and properdin (P) amplify reactions after they have been initiated. For this reason, the classical pathway is sometimes known as the properdin pathway.
The Complement System in Retinal Detachment with Choroidal Detachment
Published in Current Eye Research, 2022
Shasha Luo, Yanghao Chen, Lufei Yang, Xuechun Gong, Zhifeng Wu
The complement system plays a crucial role in the host's defense against infection and in regulating immune and inflammatory responses.3 Complement activation can be achieved through three distinct pathways: the classical pathway, the alternative pathway, and the lectin pathway. Complement activation results in the production of several biologically active molecules such as complement C3a, complement C5a, and the membrane attack complex (MAC). These molecules eliminate the foreign cells, bacteria, and viruses, but persistent inflammatory responses can injure host cells.4 Interestingly, a chronically low level of complement activation is always present in normally functioning eyes. This phenomenon is attributed to the presence of complement regulatory proteins (CRegs) that strictly control complement activation, so that the biological activity of complement proteins is directed against foreign factors rather than the host's own tissue.5
Complement cascade on severe traumatic brain injury patients at the chronic unconscious stage: implication for pathogenesis
Published in Expert Review of Molecular Diagnostics, 2018
Wangxiao Bao, Fangping He, Lihua Yu, Jian Gao, Fanxia Meng, Yahui Ding, Hai Zou, Benyan Luo
Activation of complement system consists of three pathways: the classical, the alternative, and the lectin pathway. The level of C3 convertase shows a central position at complement cascade among these pathways. Classical C3 convertase cleaves C3, the most abundant component of the complement cascade, into an activated peptide C3b [17]. The alternative route to complement is initiated by spontaneous hydrolysis of C3 in plasma. Previous studies suggested that 80% of the complement activation products result from the influence of alternative pathway [18]. The lectin pathway for complement activation begins with mannose-binding lectins (MBLs), which were previously suspected as prominent complement products in severe neuro-trauma [19,20]. C9, a key component of the membrane attack complex (MAC) in the terminal pathway, was observed higher following TBI [17,21]. MAC, a determinant of axonal damage after severe brain injury, contributes to exacerbating degeneration, impairing nerve regeneration, and recovery of function [22]. Upregulation of the innate immune response and activation of the complement system has been demonstrated early after TBI and has been linked to an exacerbated inflammatory response with subsequent brain edema, neuronal apoptosis, and cell death [23]
Targeting the complement system in neuromyelitis optica spectrum disorder
Published in Expert Opinion on Biological Therapy, 2021
Nithi Asavapanumas, Lukmanee Tradtrantip, Alan S. Verkman
The complement system is part of the innate immune system that facilitates clearance of pathogens by antibodies and phagocytic cells. While complement normally has a beneficial role, its overactivation or misdirected activation can be deleterious. Figure 1A diagrams the classical, alternative, and lectin complement pathways as relevant to AQP4-IgG seropositive NMOSD and its treatment by complement-targeted drugs. AQP4-IgG binding to AQP4 at the astrocyte plasma membrane initiates activation of the classical pathway by C1q binding to the Fc region of AQP4-IgG, resulting in assembly of the C3 convertase that cleaves C3 to C3a and C3b. Binding of C3b to factor Bb forms the C3 convertase for the alternative pathway, which amplifies the cascade. C3b also binds to the C3 convertase to form the C5 convertase that cleaves C5 to C5a and C5b. C5b complexes serially with C6, C7, C8 and C9 to form MAC (C5b-9), which acts as a permeability pore to cause cell injury [38,39].
Related Knowledge Centers
- Adaptive Immune System
- Antibody
- Inflammation
- Innate Immune System
- Protein
- Immune System
- Liver
- Cell Membrane
- Phagocytosis
- Protein Precursor