scholarly journals Supervision of The Complement System by Toxoplasma During Neural Infections (Areview)

2021 ◽  
Vol 923 (1) ◽  
pp. 012047
Author(s):  
Mohenned A. Alsaadawi ◽  
Sura S. Alkhuzaie ◽  
Yassir D. Alasadiy ◽  
Nawar Jasim Alsalih ◽  
Ali Mosa Rashid Al-Yasari
Keyword(s):  
Toxoplasma Gondii ◽  
Immune Cells ◽  
Complement System ◽  
Defense Mechanism ◽  
Chronic Infections ◽  
The Third ◽  
Intracellular Parasites ◽  
The Relationship ◽  
The Complement System ◽  
The Brain

Abstract Chronic infections with Toxoplasma gondii occur in the brain of mammalian hosts. The understanding of the relationship between Toxoplasma gondii, CNS, and the immune system assists in comprehending how Toxoplasma affects the complement system and how it exerts a defense mechanism against Toxoplasma. This review focuses on the supervision of the complement system by Toxoplasma gondii during neural infections. There are three possible mechanisms by which the protozoan can invade the brain. Tachyzoites in bloodstreams multiply, invade, and bind to endothelial cells before migrating into parenchymas via transcellular crossing mechanisms. Secondly, the immune cells become like the Trojan horse, which carries intracellular parasites across the blood–brain barrier (BBB). In the third mechanical process, the BBB can directly be crossed through the brain at the tight junction (TJ) by the tachyzoites. It is concluded that C3 manipulation of the integrity of the BBB can be used to increase T.gondii invasion into the CNS..

scholarly journals Halting targeted and collateral damage to red blood cells by the complement system

2021 ◽  
Author(s):  
M. Jalink ◽  
E. C. W. de Boer ◽  
D. Evers ◽  
M. Q. Havinga ◽  
J. M. I. Vos ◽  
...  
Keyword(s):  
Red Blood Cells ◽  
Complement System ◽  
Blood Cells ◽  
Defense Mechanism ◽  
Standard Of Care ◽  
Complement Protein ◽  
Complement Inhibition ◽  
Complement Inhibitors ◽  
The Complement System ◽  
Patient Burden

AbstractThe complement system is an important defense mechanism against pathogens; however, in certain pathologies, the system also attacks human cells, such as red blood cells (RBCs). In paroxysmal nocturnal hemoglobinuria (PNH), RBCs lack certain complement regulators which sensitize them to complement-mediated lysis, while in autoimmune hemolytic anemia (AIHA), antibodies against RBCs may initiate complement-mediated hemolysis. In recent years, complement inhibition has improved treatment prospects for these patients, with eculizumab now the standard of care for PNH patients. Current complement inhibitors are however not sufficient for all patients, and they come with high costs, patient burden, and increased infection risk. This review gives an overview of the underlying pathophysiology of complement-mediated hemolysis in PNH and AIHA, the role of therapeutic complement inhibition nowadays, and the high number of complement inhibitors currently under investigation, as for almost every complement protein, an inhibitor is being developed. The focus lies with novel therapeutics that inhibit complement activity specifically in the pathway that causes pathology or those that reduce costs or patient burden through novel administration routes.

scholarly journals The potential role of chemotaxis and the complement system in the formation and progression of thoracic aortic aneurysms inferred from the weighted gene coexpression network analysis

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Chuxiang Lei ◽  
Dan Yang ◽  
Wenlin Chen ◽  
Haoxuan Kan ◽  
Fang Xu ◽  
...  
Keyword(s):  
Network Analysis ◽  
Clinical Significance ◽  
Immune Cells ◽  
Complement System ◽  
Aortic Wall ◽  
Gene Coexpression Network ◽  
Hub Genes ◽  
Gene Coexpression ◽  
The Complement System ◽  
Coexpression Network Analysis

Abstract Background Thoracic aortic aneurysm (TAA) can be life-threatening due to the progressive weakening and dilatation of the aortic wall. Once the aortic wall has ruptured, no effective pharmaceutical therapies are available. However, studies on TAA at the gene expression level are limited. Our study aimed to identify the driver genes and critical pathways of TAA through gene coexpression networks. Methods We analyzed the genetic data of TAA patients from a public database by weighted gene coexpression network analysis (WGCNA). Modules with clinical significance were identified, and the differentially expressed genes (DEGs) were intersected with the genes in these modules. Gene Ontology and pathway enrichment analyses were performed. Finally, hub genes that might be driving factors of TAA were identified. Furthermore, we evaluated the diagnostic accuracy of these genes and analyzed the composition of immune cells using the CIBERSORT algorithm. Results We identified 256 DEGs and two modules with clinical significance. The immune response, including leukocyte adhesion, mononuclear cell proliferation and T cell activation, was identified by functional enrichment analysis. CX3CR1, C3, and C3AR1 were the top 3 hub genes in the module correlated with TAA, and the areas under the curve (AUCs) by receiver operating characteristic (ROC) analysis of all the hub genes exceeded 0.7. Finally, we found that the proportions of infiltrating immune cells in TAA and normal tissues were different, especially in terms of macrophages and natural killer (NK) cells. Conclusion Chemotaxis and the complement system were identified as crucial pathways in TAA, and macrophages with interactive immune cells may regulate this pathological process.

scholarly journals The relationship between complement C3 expression and the MUC5B genotype in pulmonary fibrosis

2018 ◽  
Vol 315 (1) ◽  
pp. L1-L10 ◽  
Author(s):  
Tsukasa Okamoto ◽  
Susan K. Mathai ◽  
Corinne E. Hennessy ◽  
Laura A. Hancock ◽  
Avram D. Walts ◽  
...  
Keyword(s):  
Pulmonary Fibrosis ◽  
Lung Injury ◽  
Lung Tissue ◽  
Complement System ◽  
Fold Increase ◽  
Complement C3 ◽  
Healthy Controls ◽  
C3 Gene ◽  
The Relationship ◽  
The Complement System

The common gain-of-function MUC5B promoter variant ( rs35705950 ) is the strongest risk factor for the development of idiopathic pulmonary fibrosis (IPF). While the role of complement in IPF is controversial, both MUC5B and the complement system play a role in lung host defense. The aim of this study was to evaluate the relationship between complement component 3 (C3) and MUC5B in patients with IPF and in bleomycin-induced lung injury in mice. To do this, we evaluated C3 gene expression in whole lung tissue from 300 subjects with IPF and 175 healthy controls. Expression of C3 was higher in IPF than healthy controls {1.40-fold increase [95% confidence interval (CI) 1.31–1.50]; P < 0.0001} and even greater among IPF subjects with the highest-risk IPF MUC5B promoter genotype [TT vs. GG = 1.59-fold (95% CI 1.15–2.20); P < 0.05; TT vs. GT = 1.66-fold (95% CI 1.20–2.30); P < 0.05]. Among subjects with IPF, C3 expression was significantly higher in the lung tissue without microscopic honeycombing than in the lung tissue with microscopic honeycombing [1.40-fold increase (95% CI 1.23– 1.59); P < 0.01]. In mice, while bleomycin exposure increased Muc5b protein expression, C3-deficient mice were protected from bleomycin-induced lung injury. In aggregate, our findings indicate that the MUC5B promoter variant is associated with higher C3 expression and suggest that the complement system may contribute to the pathogenesis of IPF.

Introduction to the complement system

1984 ◽  
Vol 306 (1129) ◽  
pp. 279-281 ◽  
Keyword(s):  
Humoral Immunity ◽  
Complement System ◽  
Bacterial Infections ◽  
Cross Linking ◽  
Complement Components ◽  
The Third ◽  
Effector Mechanism ◽  
The Complement System

Complement is the essential effector mechanism in humoral immunity to infection. Combination of antibody with antigen causes cross-linking, leading to precipitation of soluble antigens and agglutination of particular antigens, but no more. Unless complement is also present, agglutinated microorganisms can, in appropriate media in vitro grow out and form as lethal a culture as if not reacted with antibody. That this is also true in vivo is apparent from experience with patients with inherited deficiencies in complement components. The pattern is complex because of the presence of two pathways of activation, but in the rare cases of deficiency of the third component, C3, which is central to both pathways, the individuals are susceptible to repeated bacterial infections similar to aggammaglobulinaemics who are unable to synthesize antibodies. Both antibodies and complement are essential for effective humoral immunity.

scholarly journals C3c intrathecal synthesis evaluation in patients with multiple sclerosis

2007 ◽  
Vol 65 (3b) ◽  
pp. 800-802 ◽  
Author(s):  
Bárbara Padilla-Docal ◽  
Alberto J Dorta-Contreras ◽  
Hermes Fundora-Hernández ◽  
Elena Noris-García ◽  
Raisa Bu-Coifiu-Fanego ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Complement System ◽  
Progressive Disease ◽  
Degradation Process ◽  
Intrathecal Synthesis ◽  
Brain White Matter ◽  
The Central Nervous System ◽  
The Moment ◽  
The Complement System ◽  
The Brain

INTRODUCTION: Multiple sclerosis (MS) is a chronic, inflammatory and progressive disease of the central nervous system in which local inflammatory injuries of the brain white matter appears, being the most outstanding feature the myeline loss (demyelination). OBJECTIVE: To determine if the complement system might be involved in the MS immunopathogeny favouring the mechanism intervening in the myelin destruction. METHOD: Samples of sera and CSF from twelve patients with a diagnosis of MS obtained at the moment of the admission to the hospital at the beginning of the break out, were collected. Levels of C3c and albumin in sera and in CSF were quantified using radial immunodiffusion plates. RESULTS: High values over 80% of intrathecal synthesis were obtained except in one of the patients. CONCLUSION: Intrathecal synthesis of C3c and its liberation to the CSF means that the activation of the complement system in any of the two ways has taken place, and that once performed its biological functions, has suffered a degradation process.

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