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The Inflammatory Response: A Bridge Between The Constitutive and Inducible Systems
Published in Julius P. Kreier, Infection, Resistance, and Immunity, 2022
A third pathway is activated by binding of marinóse binding lectin (MBL) to mannose residues on micro-organisms. MBL is produced by liver cells as a rapid response to inflammation. Binding of MBL to micro-organisms allows subsequent binding and activation of a serum serine protease that can cleave and activate complement factor 4. This facilitates the activation of downstream components of the complement cascade. The alternative and MBL-activated pathways of complement activation are important constituents of innate immunity.
Dermal filler complications and management
Published in Michael Parker, Charlie James, Fundamentals for Cosmetic Practice, 2022
The cascading nature of complement protein activation allows for rapid amplification of a signal, and therefore a trace amount of pathogenic material can result in a large and coordinated immune response. There are three main ways in which the complement cascade can be activated: The classical pathway occurs when IgG or IgM antibodies bind to and form a complex with microbial antigens with resultant phagocytosis, cytolysis and inflammation.The alternative pathway does not rely on antibodies but instead is triggered by interactions between lipid-carbohydrate complexes on the surface of microbes.The lectin pathway is initiated when macrophages digest microbes and release chemicals which stimulate the liver to produce proteins called lec-tins which bind to carbohydrates on the surface of microbes. All three of the preceding pathways can initiate the complement cascade; however, they are not independent entities and all three may be activated independently of one another at various stages of the immune response to infection.
The Acute Phase Complement Proteins
Published in Andrzej Mackiewicz, Irving Kushner, Heinz Baumann, Acute Phase Proteins, 2020
The C3 protein is a principle source of biologically active cleavage products that mediate inflammation, solubilize and clear immune complexes, and further propogate the complement cascade, resulting in assembly of the terminal complement protein complex (the membrane attack complex, MAC) and cytolysis via the generation of discrete membrane channels. The complement effector proteins are controlled by an elaborate network of regulatory proteins, some of which also serve as cell-surface receptors for complement activation products. A detailed account of the complement effector and regulatory genes and gene products is beyond the scope of this chapter. The reader should consult relatively recent reviews.9-11
Cytological and functional effect of complement 3a on Human Scleral Fibroblasts
Published in Cutaneous and Ocular Toxicology, 2023
Kang Xiao, Ying Jie, Mingyue Luo, Qin Long
Among the bioinformation network involved in myopic progression, the complement system is considered one of the major effector mechanisms involved in the initiation of low-grade systemic or local inflammation and multiple tissue remodelling processes [12,13]. The activation of the complement cascade occurs by three major pathways: classical, lectin, and alternative. Complement 3 (C3) is the key component in the complement cascade, with the cleavage of C3 and the formation of C3a marking the activation of the complement system [14], which further forms the C5b-9, eventually triggering cell lysis or a sublytic attack. Meanwhile, cells protect themselves from excessive complement activation through CD59, which prevents the formation of C5b-9 complexes. Our previous study revealed that patients with pathological myopia (PM) have significantly higher serum C3 levels than age- and gender-matched normal controls [15]. Furthermore, our experimental myopia model provides evidence of the up-regulation of C3 in posterior scleral fibroblasts [16]. However, the precise influence of elevated C3 on scleral fibroblasts, and its potential role in the myopia development has been unknown.
C5 inhibitors are not C5a inhibitors
Published in Expert Review of Anti-infective Therapy, 2023
Endry H.T. Lim, Alexander P.J. Vlaar, Sanne de Bruin, Matthijs C. Brouwer, Diederik van de Beek
With great interest, we read the systematic review and meta-analysis by Tsai and colleagues describing the efficacy and safety of complement C5a inhibitors for patients with severe COVID-19 [1]. Their analysis show an important role for C5a inhibitors in reducing mortality in patients with severe COVID-19. However, in their study, the authors erroneously classified C5 inhibitors ravulizumab, eculizumab, and zilucoplan as C5a inhibitors. Upon activation of the final common pathway of the complement cascade, C5 is cleaved into C5a and C5b. C5a is an anaphylatoxin causing a strong pro-inflammatory response, whereas C5b couples with other complement factors to form the C5b-9 membrane attack complex (MAC) [2]. The latter is important for bacterial killing, and inhibition of C5b increases the risk of bacterial infections [2–5]. C5 inhibitors, therefore, exert different effects by blocking both C5a and C5b when compared to specific C5a inhibitors, such as the monoclonal antibody vilobelimab [5–7].
Zilucoplan: An Investigational Complement C5 Inhibitor for the Treatment of Acetylcholine Receptor Autoantibody–Positive Generalized Myasthenia Gravis
Published in Expert Opinion on Investigational Drugs, 2021
James F. Howard, John Vissing, Nils E. Gilhus, M. Isabel Leite, Kimiaki Utsugisawa, Petra W. Duda, Ramin Farzaneh-Far, Hiroyuki Murai, Heinz Wiendl
Complement-mediated destruction of the NMJ, initiated by the presence of pathogenic autoantibodies, is a major cause of MG pathology [26,28,32,33]. The complement cascade is a critical part of the immune system that is initiated by any one of three separate pathways (alternative, classical, and lectin; Figure 1A). All three pathways first converge at complement component 3 (C3), with a second convergence point at C5. C5 is cleaved to produce C5a and C5b, with subsequent recruitment of C6, C7, C8, and C9 to yield the pore-like terminal complement complex C5b-9, also known as the membrane attack complex (MAC) [32,34]. Accumulation of the MAC on the postsynaptic plasma membrane of the NMJ mediates tissue damage and destruction of the delicate cytoarchitecture and electrochemical integrity of the postsynaptic membrane (Figure 1B) [27,32]. The complement cascade is implicated as a key mediator of cell and tissue damage in numerous other inflammatory and autoimmune disorders including immune-mediated necrotizing myopathies [35], paroxysmal nocturnal hemoglobinuria [36], neuromyelitis optica [37], and atypical hemolytic uremic syndrome [38]. It has been hypothesized that complement and inflammation also play a role in amyotrophic lateral sclerosis [39].