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Immune system and Innate Immunity
Published in Peter Kam, Ian Power, Michael J. Cousins, Philip J. Siddal, Principles of Physiology for the Anaesthetist, 2020
Peter Kam, Ian Power, Michael J. Cousins, Philip J. Siddal
The three ways by which the complement system may be activated are: The classical pathway that is activated by immune complexes, initiated by the binding of C1q to the Fc portion of immunoglobulin.The alternative pathway that occurs in the fluid phase or on contact with foreign surfaces and is initiated by C3 activation.The lectin pathway initiated by mannose-binding lectin (MBL) which binds to carbohydrate (sugar) on bacteria and activates C4 and the classical pathway.
Inflammation and immunology
Published in C. Simon Herrington, Muir's Textbook of Pathology, 2020
Christopher Bellamy, Stephen J. Jenkins, Henry J. McSorley, David A. Dorward, Timothy J. Kendall
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.
Primary immunodeficiency diseases
Published in Gabriel Virella, Medical Immunology, 2019
John W. Sleasman, Gabriel Virella
Defects in the early classical pathway (C1q, C2, and C4) result in SLE-like symptoms and increased susceptibility to infection with encapsulated bacteria. Deficiencies in late components of the membrane attack complex (C5, C6, C7, C8, and C9) place patients at risk for disseminated Neisseria infections, as does Properdin and factor D deficiencies in the alternative pathway. Deficiencies in the mannose binding lectin pathway include mannose binding lectin serine protease 2 (MASP2) deficiency and Ficolin 3 deficiency. Both result in varying degrees of increased susceptibility to recurrent pyogenic infections. Abnormalities of factor H and factor I result in recurrent atypical hemolytic uremic syndrome. Deficiency in factor H and I results in a secondary fourfold increase in the catabolic rate of C3 complement component. Patients are prone to recurrent pyogenic infections, particularly with encapsulated bacteria such as S. pneumoniae and N. meningitidis. They are also prone to the development of immune complex disease. “Anaphylactoid” reactions secondary to the spontaneous generation of C3a are also frequently observed in these patients.
In silico structural inhibition of ACE-2 binding site of SARS-CoV-2 and SARS-CoV-2 omicron spike protein by lectin antiviral dyad system to treat COVID-19
Published in Drug Development and Industrial Pharmacy, 2022
Anand Kumar Pandey, Shalja Verma
Mannose-binding lectin (MBL) proteins have exclusive ability to recognize carbohydrates present on surfaces of distinct cells and are the key players which mediate innate immunity especially via complement lectin pathway, before the development of specific adaptive immune response. They show strong affinity for viral glycoproteins and bind them via carbohydrate moieties [12]. Past study reported reduction in MBL proteins levels in serum of SARS-CoV infected patients [13,14]. Also, MBL inhibited infectivity of virus in rhesus fetal kidney cells, thereby proving antiviral role of MBL against SARS-CoV [15]. MBL by activating the complement system and increasing the influx rate of immune cells associated with innate immunity to the site of infection increases virus neutralization and thus hinders the virus from invading the alveolar cells [16]. Many studies have reported antiviral, antimicrobial and anticarcinogenic properties of lectins [14]. Also, some studies have reported antiviral effect of lectins against human immune deficiency syndrome virus (HIV) and other coronaviruses [17–19]. Though several review reports have suggested effectiveness of lectins against SARS-CoV-2 but no such experimental studies have yet been conducted for validating the efficacy of lectins against the SARS-CoV-2 and its variant form SARS-CoV-2 omicron.
Understanding the genetic basis of immune responses to fungal infection
Published in Expert Review of Anti-infective Therapy, 2022
Samuel M. Gonçalves, Cristina Cunha, Agostinho Carvalho
Besides PRRs, several soluble mediators interact with and bind to microbial polysaccharides without transducing intracellular signals and function as opsonins to facilitate phagocytosis [15]. Among these, mannose-binding lectin (MBL) binds carbohydrate patterns from pathogens and activates the lectin pathway of the complement system. Several studies have disclosed common genetic variation in MBL to regulate its expression levels, functional activity, or both [47]. Except for cryptococcosis in HIV-uninfected patients [48], the contribution of genetic variation in MBL to invasive disease has not been addressed, although the levels of circulating protein were found to vary significantly during IPA [49], invasive candidiasis [50], and pneumonia by Pneumocystis jirovecii [51]. Likewise, SNPs in the triggering receptor expressed on myeloid cells 1 (TREM1) were found to influence the levels of soluble TREM1 as well as TREM1-mediated cytokine production in response to stimulation with A. fumigatus [52], despite no evidence for a direct association with human infection has been reported thus far.
Activation of Complement System in Henoch-Schönlein Purpura Nephritis
Published in Fetal and Pediatric Pathology, 2022
Hea Min Jang, Heesun Baek, Man Hoon Han, Yong Jin Kim, Chan-Duck Kim, Yong-Lim Kim, Sun-Hee Park, Min Hyun Cho
Many reports have suggested that the pathophysiology of IgAN is associated with complement activation [8,9,17]. Complement activation is initiated by mesangial IgA-immune complex (IgA-IC) deposition. In early studies, IgAN was associated with alternative pathways, but recently Roos et al. suggested that the lectin pathway plays an important role. The lectin pathway of complement is activated by the interaction of the plasma lectins, mannose-binding lectin (MBL), L-ficolin, or H-ficolin, with their carbohydrate ligands. It induces the activation of MBL-associated serine proteases (MASPs), and activated MASP-2 produces C4b2a and induces C3 cleavage [9]. Investigators found that, among 60 IgAN patients, 25% of renal biopsy had positive glomerular staining for MBL, and L-ficolin was positive for all MBL-positive patients [9]. With or without MBL staining, C3 deposition was positive in most biopsies, but C1q was negative. This suggests that the alternative pathway was activated in 75% of patients with IgAN, and the glomerular lectin pathway was involved in 25% of IgAN in that study.