scholarly journals PARTICULAR QUALITIES OF THE PROTEOLYTIC SYSTEM IN PATIENTS WITH TUBERCULOSIS DEPENDING ON THE SENSITIVITY OF THE PATHOGEN

2021 ◽  
Vol 74 (1) ◽  
pp. 94-97
Author(s):  
Igor D. Duzhyi ◽  
Halyna P. Oleshchenko ◽  
Ivan A. Hnatenko ◽  
Stanislav O. Holubnychyi
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Pleural Effusion ◽  
Pulmonary Tuberculosis ◽  
Neutrophil Elastase ◽  
Proteolytic System ◽  
The Third ◽  
Pleural Tuberculosis ◽  
Dual Localization ◽  
Tuberculous Pleurisy

The aim: Studying the features of the proteolytic system in patients with tuberculosis depending on the sensitivity of the pathogen. Materials and methods: In the course of the research we studied the level of elastase in the blood of 111 patients. The first group consisted of 66 (59.5%) people with pulmonary tuberculosis (39 were sensitive to antibacterial drugs, 27 were resistant). The second group included 13 (11.7%) patients with tuberculous pleurisy. The third group consisted of 32 (28.8%) patients with dual localization of the process (pulmonary tuberculosis and pleural tuberculosis). Results: The level of neutrophil elastase in patients with tuberculous pleurisy (253.2 nmol / min • ml) was 2.2 times higher than in patients with sensitive pulmonary tuberculosis (110.1 nmol / min • ml) and higher than in patients with resistant pulmonary tuberculosis 3.0 times. In combined pulmonary and pleural tuberculosis (third group) the level of elastase was 1.6 times higher than in pulmonary tuberculosis (176.9 nmol / min • ml)) (p <0.01), but lower than in pleurisy in 1, 4 times. In sensitive combined tuberculosis (lungs and pleura) the level of NE was 1.5 times higher than in patients of subgroup 1a (p <0.01) and 1.4 times lower than in patients with tuberculous pleurisy (p <0.01 ). Conclusions: The highest level of elastase in tuberculous pleurisy can be explained by its increased production, contributes to increased “permeability” of the pleural sheets and the accumulation of pleural effusion. In resistant forms of tuberculosis, the immune response in the form of the activity of the proteolytic system, which is lower than in sensitive forms, can be explained by the exhaustion of the immune system under the influence of aggressive tuberculosis. The above can be associated with both the weakening of the patient’s body and the aggressiveness of the pathogen.

scholarly journals Papain-Like Proteases as Coronaviral Drug Targets: Current Inhibitors, Opportunities, and Limitations

2020 ◽  
Vol 13 (10) ◽  
pp. 277 ◽  
Author(s):  
Anastasiia I. Petushkova ◽  
Andrey A. Zamyatnin
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Severe Acute Respiratory Syndrome ◽  
Viral Genome ◽  
Drug Targets ◽  
Structural Features ◽  
The Third ◽  
Frequent Mutations ◽  
Near Future ◽  
Viral Reproduction

Papain-like proteases (PLpro) of coronaviruses (CoVs) support viral reproduction and suppress the immune response of the host, which makes CoV PLpro perspective pharmaceutical targets. Their inhibition could both prevent viral replication and boost the immune system of the host, leading to the speedy recovery of the patient. Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is the third CoV outbreak in the last 20 years. Frequent mutations of the viral genome likely lead to the emergence of more CoVs. Inhibitors for CoV PLpro can be broad-spectrum and can diminish present and prevent future CoV outbreaks as PLpro from different CoVs have conservative structures. Several inhibitors have been developed to withstand SARS-CoV and Middle East respiratory syndrome CoV (MERS-CoV). This review summarizes the structural features of CoV PLpro, the inhibitors that have been identified over the last 20 years, and the compounds that have the potential to become novel effective therapeutics against CoVs in the near future.

scholarly journals A Biofilm Matrix-Associated Protease Inhibitor ProtectsPseudomonas aeruginosafrom Proteolytic Attack

mBio ◽  
2018 ◽  
Vol 9 (2) ◽  
Author(s):  
Boo Shan Tseng ◽  
Courtney Reichhardt ◽  
Gennifer E. Merrihew ◽  
Sophia A. Araujo-Hernandez ◽  
Joe J. Harrison ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Protease Inhibitor ◽  
Neutrophil Elastase ◽  
Matrix Protein ◽  
Lipid Vesicles ◽  
Matrix Proteins ◽  
Host Immune System ◽  
Content Type ◽  
Biofilm Matrix

ABSTRACTPseudomonas aeruginosaproduces an extracellular biofilm matrix that consists of nucleic acids, exopolysaccharides, lipid vesicles, and proteins. In general, the protein component of the biofilm matrix is poorly defined and understudied relative to the other major matrix constituents. While matrix proteins have been suggested to provide many functions to the biofilm, only proteins that play a structural role have been characterized thus far. Here we identify proteins enriched in the matrix ofP. aeruginosabiofilms. We then focused on a candidate matrix protein, the serine protease inhibitor ecotin (PA2755). This protein is able to inhibit neutrophil elastase, a bactericidal enzyme produced by the host immune system duringP. aeruginosabiofilm infections. We show that ecotin binds to the key biofilm matrix exopolysaccharide Psl and that it can inhibit neutrophil elastase when associated with Psl. Finally, we show that ecotin protects both planktonic and biofilmP. aeruginosacells from neutrophil elastase-mediated killing. This may represent a novel mechanism of protection for biofilms to increase their tolerance against the innate immune response.IMPORTANCEProteins associated with the extracellular matrix of bacterial aggregates called biofilms have long been suggested to provide many important functions to the community. To date, however, only proteins that provide structural roles have been described, and few matrix-associated proteins have been identified. We developed a method to identify matrix proteins and characterized one. We show that this protein, when associated with the biofilm matrix, can inhibit a bactericidal enzyme produced by the immune system during infection and protect biofilm cells from death induced by the enzyme. This may represent a novel mechanism of protection for biofilms, further increasing their tolerance against the immune response. Together, our results are the first to show a nonstructural function for a confirmed matrix-interacting protein.

scholarly journals Diagnostic value of pleural fluid adenosine deaminase among the patients with pleural tuberculosis

2019 ◽  
Author(s):  
Fariborz Rousta ◽  
Mohsen Sokouti ◽  
Samad Beheshty Rouy ◽  
Sina Parsay
Keyword(s):  
Pleural Effusion ◽  
Adenosine Deaminase ◽  
Pleural Fluid ◽  
Predictive Value ◽  
Pathology Report ◽  
Tuberculous Lymphadenitis ◽  
Pleural Tuberculosis ◽  
Multiple Biopsies ◽  
Tuberculous Pleurisy ◽  
Exudative Pleural Effusion

Abstract Purpose Extra-pulmonary tuberculosis occurs in about 10-20% of patients most commonly as tuberculous lymphadenitis or pleural effusion. Pleural fluid Adenosine deaminase (ADA) activity considered as a useful biomarker for detecting pleural tuberculosis. The purpose of this study was to evaluate the diagnostic accuracy of pleural fluid adenosine deaminase level in patients with pleural tuberculosis. Methods In this cross-sectional study, 113 patients with exudative pleural effusion with unknown underlying diagnosis, were enrolled. Physical examination, chest CT, measurement of ADA level of pleural fluid, direct thoracoscopic examination, and biopsy of pleura were performed for all individuals. Results The diagnosis of tuberculous pleurisy was established in 40 individuals regarding the pathology report of biopsy samples. The mean ADA level of the TB and the non-TB group was 39.90±22.93 IU/L and 30.74±38.27 IU/L respectively, which was not statistically significant (P-value=0.167). Sensitivity, specificity, positive predictive value, and negative predictive value of ADA test were 35%, 86.30%, 58.33%, and 70.79%, respectively. Conclusion Based on low sensitivity and specificity of ADA test, in patients with unexplained exudative pleural effusion especially in those who were suspicious for tuberculous pleurisy, despite the low level of ADA, direct thoracoscopic pleural observation and multiple biopsies of pleura is highly recommended.

scholarly journals Review of Pathologies on MOR 693: An Allosaurus from the Late Jurassic of Wyoming and Implications for Understanding Allosaur Immune Systems

2019 ◽  
Author(s):  
Jack Wilkin
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Soft Tissue ◽  
Late Jurassic ◽  
Tissue Preservation ◽  
Immune Systems ◽  
Soft Tissue Preservation ◽  
The Third ◽  
Bone Infections ◽  
The Right

Palaeopathology is important as it provides remarkable insights into the lifestyles of dinosaurs and other prehistoric animals. The Late Jurassic Allosaurus known as Big Al (MOR 693) from Big Horn County, Wyoming preserves at least 19 injuries. About 2% of all bones showed abnormalities, including osteomyelitis on the right foot, on the first phalanx of the third toe, which may have contributed to the animal's death. There would likely have been many more pathologies that did not make it into the paleontological record due do the lack of soft-tissue preservation. Analysis of MOR 693’s immune response to bone infections and comparing it to other theropods, we can confidently say that dinosaurs possessed an immune system that isolated and localized infections like extant Aves.

scholarly journals Secondary haemophagocytic lymphohistiocytosis in COVID-19: correlation of the autopsy findings of bone marrow haemophagocytosis with HScore

2021 ◽  
pp. jclinpath-2020-207337
Author(s):  
Claudia Núñez-Torrón ◽  
Ana Ferrer-Gómez ◽  
Esther Moreno Moreno ◽  
Belen Pérez-Mies ◽  
Jesús Villarrubia ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Immune Response ◽  
Immune System ◽  
Multiorgan Failure ◽  
Histological Findings ◽  
Haemophagocytic Lymphohistiocytosis ◽  
Bone Marrow Tissue ◽  
Autopsy Findings ◽  
Specific Finding ◽  
Clinical Records

BackgroundSecondary haemophagocytic lymphohistiocytosis (sHLH) is characterised by a hyper activation of immune system that leads to multiorgan failure. It is suggested that excessive immune response in patients with COVID-19 could mimic this syndrome. Some COVID-19 autopsy studies have revealed the presence of haemophagocytosis images in bone marrow, raising the possibility, along with HScore parameters, of sHLH.AimOur objective is to ascertain the existence of sHLH in some patients with severe COVID-19.MethodsWe report the autopsy histological findings of 16 patients with COVID-19, focusing on the presence of haemophagocytosis in bone marrow, obtained from rib squeeze and integrating these findings with HScore parameters. CD68 immunohistochemical stains were used to highlight histiocytes and haemophagocytic cells. Clinical evolution and laboratory parameters of patients were collected from electronic clinical records.ResultsEleven patients (68.7%) displayed moderate histiocytic hyperplasia with haemophagocytosis (HHH) in bone marrow, three patients (18.7%) displayed severe HHH and the remainder were mild. All HScore parameters were collected in 10 patients (62.5%). Among the patients in which all parameters were evaluable, eight patients (80%) had an HScore >169. sHLH was not clinically suspected in any case.ConclusionsOur results support the recommendation of some authors to use the HScore in patients with severe COVID-19 in order to identify those who could benefit from immunosuppressive therapies. The presence of haemophagocytosis in bone marrow tissue, despite not being a specific finding, has proved to be a very useful tool in our study to identify these patients.

scholarly journals The immune response of T cells and therapeutic targets related to regulating the levels of T helper cells after ischaemic stroke

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Tian-Yu Lei ◽  
Ying-Ze Ye ◽  
Xi-Qun Zhu ◽  
Daniel Smerin ◽  
Li-Juan Gu ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Immune System ◽  
Immune Responses ◽  
Ischaemic Stroke ◽  
Immune Cells ◽  
Tissue Injury ◽  
Recovery Period ◽  
Vital Functions ◽  
Anti Inflammatory

AbstractThrough considerable effort in research and clinical studies, the immune system has been identified as a participant in the onset and progression of brain injury after ischaemic stroke. Due to the involvement of all types of immune cells, the roles of the immune system in stroke pathology and associated effects are complicated. Past research concentrated on the functions of monocytes and neutrophils in the pathogenesis of ischaemic stroke and tried to demonstrate the mechanisms of tissue injury and protection involving these immune cells. Within the past several years, an increasing number of studies have elucidated the vital functions of T cells in the innate and adaptive immune responses in both the acute and chronic phases of ischaemic stroke. Recently, the phenotypes of T cells with proinflammatory or anti-inflammatory function have been demonstrated in detail. T cells with distinctive phenotypes can also influence cerebral inflammation through various pathways, such as regulating the immune response, interacting with brain-resident immune cells and modulating neurogenesis and angiogenesis during different phases following stroke. In view of the limited treatment options available following stroke other than tissue plasminogen activator therapy, understanding the function of immune responses, especially T cell responses, in the post-stroke recovery period can provide a new therapeutic direction. Here, we discuss the different functions and temporal evolution of T cells with different phenotypes during the acute and chronic phases of ischaemic stroke. We suggest that modulating the balance between the proinflammatory and anti-inflammatory functions of T cells with distinct phenotypes may become a potential therapeutic approach that reduces the mortality and improves the functional outcomes and prognosis of patients suffering from ischaemic stroke.

scholarly journals Why Does SARS-CoV-2 Infection Induce Autoantibody Production?

Pathogens ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 380
Author(s):  
Ales Macela ◽  
Klara Kubelkova
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Host Cell ◽  
Critical Role ◽  
Cell Interaction ◽  
Immune Recognition ◽  
Autoantibody Production ◽  
Host Cell Interaction ◽  
Primary Virus

SARS-CoV-2 infection induces the production of autoantibodies, which is significantly associated with complications during hospitalization and a more severe prognosis in COVID-19 patients. Such a response of the patient’s immune system may reflect (1) the dysregulation of the immune response or (2) it may be an attempt to regulate itself in situations where the non-infectious self poses a greater threat than the infectious non-self. Of significance may be the primary virus-host cell interaction where the surface-bound ACE2 ectoenzyme plays a critical role. Here, we present a brief analysis of recent findings concerning the immune recognition of SARS-CoV-2, which, we believe, favors the second possibility as the underlying reason for the production of autoantibodies during COVID-19.

scholarly journals MITF induces escape from innate immunity in melanoma

2021 ◽  
Vol 40 (1) ◽  
Author(s):  
Luis Sánchez-del-Campo ◽  
Román Martí-Díaz ◽  
María F. Montenegro ◽  
Rebeca González-Guerrero ◽  
Trinidad Hernández-Caselles ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Nk Cells ◽  
Nk Cell ◽  
Luciferase Reporter ◽  
Damage Repair ◽  
Reporter Assays ◽  
Underlying Mechanisms ◽  
Nk Cytotoxicity

Abstract Background The application of immune-based therapies has revolutionized cancer treatment. Yet how the immune system responds to phenotypically heterogeneous populations within tumors is poorly understood. In melanoma, one of the major determinants of phenotypic identity is the lineage survival oncogene MITF that integrates diverse microenvironmental cues to coordinate melanoma survival, senescence bypass, differentiation, proliferation, invasion, metabolism and DNA damage repair. Whether MITF also controls the immune response is unknown. Methods By using several mouse melanoma models, we examine the potential role of MITF to modulate the anti-melanoma immune response. ChIP-seq data analysis, ChIP-qPCR, CRISPR-Cas9 genome editing, and luciferase reporter assays were utilized to identify ADAM10 as a direct MITF target gene. Western blotting, confocal microscopy, flow cytometry, and natural killer (NK) cytotoxicity assays were used to determine the underlying mechanisms by which MITF-driven phenotypic plasticity modulates melanoma NK cell-mediated killing. Results Here we show that MITF regulates expression of ADAM10, a key sheddase that cleaves the MICA/B family of ligands for NK cells. By controlling melanoma recognition by NK-cells MITF thereby controls the melanoma response to the innate immune system. Consequently, while melanoma MITFLow cells can be effectively suppressed by NK-mediated killing, MITF-expressing cells escape NK cell surveillance. Conclusion Our results reveal how modulation of MITF activity can impact the anti-melanoma immune response with implications for the application of anti-melanoma immunotherapies.

scholarly journals Immune System Efficiency in Cancer and the Microbiota Influence

Pathobiology ◽  
2021 ◽  
pp. 1-17
Author(s):  
Ana Margarida Barbosa ◽  
Alexandra Gomes-Gonçalves ◽  
António G. Castro ◽  
Egídio Torrado
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Immune Checkpoint Inhibitors ◽  
Therapeutic Response ◽  
Checkpoint Inhibitors ◽  
Critical Role ◽  
Antitumor Immune Response ◽  
System Efficiency ◽  
Novel Targets ◽  
Cancer Immunosurveillance

The immune system plays a critical role in preventing cancer development and progression. However, the complex network of cells and soluble factor that form the tumor microenvironment (TME) can dictate the differentiation of tumor-infiltrating leukocytes and shift the antitumor immune response into promoting tumor growth. With the advent of cancer immunotherapy, there has been a reinvigorated interest in defining how the TME shapes the antitumor immune response. This interest brought to light the microbiome as a novel player in shaping cancer immunosurveillance. Indeed, accumulating evidence now suggests that the microbiome may confer susceptibility or resistance to certain cancers and may influence response to therapeutics, particularly immune checkpoint inhibitors. As we move forward into the age of precision medicine, it is vital that we define the factors that influence the interplay between the triad immune system-microbiota-cancer. This knowledge will contribute to improve the therapeutic response to current approaches and will unravel novel targets for immunotherapy.

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