China
Africa
Explore chapters and articles related to this topic
The Development of Improved Therapeutics through a Glycan- “Designer” Approach
Published in Peter Grunwald, Pharmaceutical Biocatalysis, 2019
Other glycans that either mimic or are derived from pathogen-associated molecular patterns (PAMPs) are recognized by mannan-binding lectins. These can activate innate immune system via mannan-binding lectin (MBL) complement pathway and drive pro-inflammatory responses.
The Role of Human Genetics in HIV-1 Infection
Published in Thomas R. O’Brien, Chemokine Receptors and AIDS, 2019
Maureen P. Martin, Mary Carrington
Mannose-binding lectin (MBL) is a member of the collectin family of proteins and is an important constituent of the innate immune system (180–182). MBL activates complement (183) and acts in the first line of defense against various bacterial, viral, and parasitic infections, before the establishment of adaptive immune protection by B and T cells (180). Low serum levels of MBL are associated with opsonization defects and impaired phagocytosis (184–186). The MBL gene is located on chromosome 10q (187,188), and polymorphisms in the first exon have been shown to be important in determining the level of circulating MBL (189,190). Single amino acid variants associated with lower MBL serum concentrations include G→D at codon 54 (allele B) (191), G→E at codon 57 (allele C) (189), and R→C at codon 52 (allele D) (190). Polymorphisms in the promoter region of the MBL gene have also been shown to affect serum concentration of MBL (192).
Defence Mechanisms
Published in John C Watkinson, Raymond W Clarke, Louise Jayne Clark, Adam J Donne, R James A England, Hisham M Mehanna, Gerald William McGarry, Sean Carrie, Basic Sciences Endocrine Surgery Rhinology, 2018
(See Figure 13.6.) The complement proteins found in the circulation and tissue fluids constitute an important defensive system that can be activated by the Fc regions of IgM and IgG antibodies in what is termed the classical pathway of complement activation. This is triggered when IgM or several IgG antibodies that are bound to antigen, interact with the complement C1 protein complex, resulting in the formation of a C3 convertase enzyme from C4 and C2 (C4b2a). This same C3 convertase can be generated when the pattern recognition molecule mannan-binding lectin (MBL) interacts with mannose residues of microbial surfaces. (MBL is a member of a family of secreted carbohydrate-binding collagenous defensive proteins called collectins.) A different C3 convertase is produced when certain complement proteins directly form a stable complex (C3bBbP) on microbial surfaces in what is termed the alternative pathway of complement activation. IgA can also activate the alternative pathway.
Anti-phospholipase A2 receptor antibodies directly induced podocyte damage in vitro
Published in Renal Failure, 2022
Yanfen Li, Juntao Yu, Miao Wang, Zhao Cui, Ming-hui Zhao
The pathogenesis of membranous nephropathy (MN) involves in situ formation of subepithelial immune deposits that induce glomerular injury by damaging podocytes through complement-dependent processes [1]. Most cases of primary MN possess autoantibodies against the podocyte antigen M-type phospholipase A2 receptor (PLA2R) [2]. The antibody levels are often associated with disease activity, treatment responses, and kidney outcomes [3–5]. A recent study [6] found that anti-PLA2R IgG4 directly bound Mannan-binding lectin in a glycosylation-dependent manner, and activated the lectin pathway of the complement cascade. Assembly of the terminal C5b-9 complex and activation of the complement receptors C3aR1 or C5aR1 were required to induce proteolysis of synaptopodin and NEPH1 and podocyte injuries.
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.