scholarly journals Bacterial Superantigen Toxins, CD28, and Drug Development

Toxins ◽  
2018 ◽  
Vol 10 (11) ◽  
pp. 459 ◽  
Author(s):  
Raymond Kaempfer
Keyword(s):  
Mhc Class Ii ◽  
Bacterial Infections ◽  
Bacterial Strains ◽  
Toxic Shock ◽  
Human Immune System ◽  
Strong Immune Response ◽  
Costimulatory Receptor ◽  
Human Immune ◽  
Receptor Dimer ◽  
Bacterial Superantigen

During severe bacterial infections, death and disease are often caused by an overly strong immune response of the human host. Acute toxic shock is induced by superantigen toxins, a diverse set of proteins secreted by Gram-positive staphylococcal and streptococcal bacterial strains that overstimulate the inflammatory response by orders of magnitude. The need to protect from superantigen toxins led to our discovery that in addition to the well-known MHC class II and T cell receptors, the principal costimulatory receptor, CD28, and its constitutively expressed coligand, B7-2 (CD86), previously thought to have only costimulatory function, are actually critical superantigen receptors. Binding of the superantigen into the homodimer interfaces of these costimulatory receptors greatly enhances B7-2/CD28 engagement, leading to excessive pro-inflammatory signaling. This finding led to the design of short receptor dimer interface mimetic peptides that block the binding of superantigen and thus protect from death. It then turned out that such a peptide will protect also from Gram-negative bacterial infection and from polymicrobial sepsis. One such CD28 mimetic peptide is advancing in a Phase 3 clinical trial to protect from lethal wound infections by flesh-eating bacteria. These host-oriented therapeutics target the human immune system itself, rendering pathogens less likely to become resistant.

scholarly journals Human CD4-major histocompatibility complex class II (DQw6) transgenic mice in an endogenous CD4/CD8-deficient background: reconstitution of phenotype and human-restricted function.

1994 ◽  
Vol 180 (5) ◽  
pp. 1911-1920 ◽  
Author(s):  
R S Yeung ◽  
J M Penninger ◽  
T M Kündig ◽  
Y Law ◽  
K Yamamoto ◽  
...  
Keyword(s):  
Major Histocompatibility Complex ◽  
Immune System ◽  
T Cell ◽  
Transgenic Mice ◽  
Mhc Class Ii ◽  
Class Ii ◽  
Major Histocompatibility ◽  
Human Immune System ◽  
Histocompatibility Complex ◽  
Human Immune

To reconstitute the human immune system in mice, transgenic mice expressing human CD4 and human major histocompatibility complex (MHC) class II (DQw6) molecules in an endogenous CD4- and CD8-deficient background (mCD4/8-/-), after homologous recombination, have been generated. We report that expression of human CD4 molecule in mCD4/8-/- mice rescues thymocyte development and completely restores the T cell compartment in peripheral lymphoid organs. Upon vesicular stomatitis virus (VSV) challenge, the reconstituted mature T cell population effectively provide T help to B cells in immunoglobulin class switching from IgM to specific IgG-neutralizing antibodies. Human CD4+DQw6+ double transgenic mice are tolerant to DQw6 and the DQw6 molecule functions in antigen presentation, effectively generating a human MHC class II-restricted T cell response to streptococcal M6C2 peptide. These data show that both the hCD4 and DQw6 molecules are functional in mCD4/8-/- mice, fully and stably reconstituting this limb of the human immune system in mice. This animal model provides a powerful in vivo tool to dissect the human CD4-human class II MHC interaction, especially its role in human autoimmune diseases, superantigen-mediated diseases, and acquired immunodeficiency syndrome (AIDS).

On the innate immune response to intracellular bacterial infections

2020 ◽  
Vol 13 (08) ◽  
pp. 2050170
Author(s):  
Irina Naskinova ◽  
Mikhail Kolev ◽  
Anka Markovska
Keyword(s):  
Bacterial Infections ◽  
Initial Conditions ◽  
Approximate Solutions ◽  
Big Data Analysis ◽  
Model System ◽  
Innate Immune ◽  
Human Immune System ◽  
Approaches To Study ◽  
Infected Cells ◽  
Human Immune

Various bacteria are able to infect human organisms to induce less or more dangerous diseases. In response to them, the human immune system is usually activated. In addition, medical therapies to the patients can be applied. One of the most popular approaches is the use of various antibiotics. However, some bacteria are able to develop resistance against the applied antibiotics. Various approaches to study these phenomena are proposed in the literature, among them tools for big data analysis, machine learning, mathematical modeling, etc. In our paper, we consider a mathematical model describing the interactions between susceptible uninfected cells, infected cells, immune cells and bacteria. We study the properties of the model. We propose numerical scheme for obtaining the approximate solutions to the model system for various values of parameters and initial conditions.

Infection, allergy and the hygiene hypothesis: historical perspective

2003 ◽  
Vol 117 (12) ◽  
pp. 946-950 ◽  
Author(s):  
D. S. Kim ◽  
A. B. Drake-Lee
Keyword(s):  
Bacterial Infections ◽  
Hygiene Hypothesis ◽  
Developed Countries ◽  
Human Immune System ◽  
Important Relationship ◽  
High Prevalence ◽  
Parasite Infections ◽  
Historical Relationship ◽  
Human Immune ◽  
The Developed Countries

The ’hygiene hypothesis’ was popularized in the late 1980s to explain the high prevalence of atopic disordersin the developed countries. It links atopic disorders and the lack of early life infections. An association between the two is not novel and dates back to the beginnings of allergy, immunology and microbiology. Allergy and infection have always been closely related and the study ofone has often provided new insights into the pathobiology of the other. Early research into bacterial infections led to the discovery of the human immune system and the concept of allergy. An important relationship exists between parasite infections and the development of atopic disorders.This review traces the long and intimate historical relationship between infection and allergy.

scholarly journals Computational Modeling of Microabscess Formation

2012 ◽  
Vol 2012 ◽  
pp. 1-16 ◽  
Author(s):  
Alexandre Bittencourt Pigozzo ◽  
Gilson Costa Macedo ◽  
Rodrigo Weber dos Santos ◽  
Marcelo Lobosco
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Computational Modeling ◽  
Bacterial Infection ◽  
Computational Model ◽  
Immune Cells ◽  
Bacterial Infections ◽  
Distinct Pattern ◽  
Human Immune System ◽  
Human Immune

Bacterial infections can be of two types: acute or chronic. The chronic bacterial infections are characterized by being a large bacterial infection and/or an infection where the bacteria grows rapidly. In these cases, the immune response is not capable of completely eliminating the infection which may lead to the formation of a pattern known as microabscess (or abscess). The microabscess is characterized by an area comprising fluids, bacteria, immune cells (mainly neutrophils), and many types of dead cells. This distinct pattern of formation can only be numerically reproduced and studied by models that capture the spatiotemporal dynamics of the human immune system (HIS). In this context, our work aims to develop and implement an initial computational model to study the process of microabscess formation during a bacterial infection.

STUDIES ON SOME BACTERIAL DISEASES IN OREOCHROMIS NILOTICUS WITH SPECIAL REFERENCES TO TREATMENT

2018 ◽  
pp. 39-47
Author(s):  
Viola Zaki ◽  
Ahmed EL-gamal ◽  
Yasmin Reyad
Keyword(s):  
Oreochromis Niloticus ◽  
Bacterial Infections ◽  
Antimicrobial Agents ◽  
Histopathological Examination ◽  
Klebsiella Oxytoca ◽  
Bacterial Isolates ◽  
Bacterial Strains ◽  
Tissue Samples ◽  
Hydropic Degeneration ◽  
Total Prevalence

he present research carried out to study the common bacterial infections in Oreochromis niloticus (Nile tilapia) in Manzala area at Dakahlia governorate and possible antimicrobial agents used for treatment. A total number of 400 fish were randomly collected from Manzala private farms at Dakahlia governorate and subjected to the clinical, bacteriological and histopathological examination. The highest prevalence of bacterial isolates during the whole period of examination of naturally infected O.niloticus was recorded for A.hydrophila (22.66%), followed by V.alginolyticus (19.01%), V.parahemolyticus (13.80%), Streptococcus spp. (12.24%), A.caviae (11.72%), V.cholera (10.16%), A.salmonicida (7.55%), while the lowest prevalence was recorded for Klebsiella oxytoca (2.86%). The seasonal highest total prevalence of bacterial isolates from examined naturally infected O. niloticus was recorded in spring (30.21%), followed by autumn (28.39%), then summer (22.40%) and the lowest prevalence was recorded in winter (19.01%). Histopathological findings of the tissue samples which collected from different organs of naturally infected O.niloticus revealed that spleen show marked hemosiderosis and sever hemorrhage, gills showsever congestion of lamellar capillaries with marked aneurysm, necrosis and hemorrhage of lamellar epithelium and liver show sever hydropic degeneration and necrosis of hepatocytes, Ciprofloxacin was the most effective antibiotic against all isolated bacterial strains

Repurposing of auranofin against bacterial infections: An In silico and In vitro study

2020 ◽  
Vol 16 ◽  
Author(s):  
Nidhi Sharma ◽  
Arti Singh ◽  
Ruchika Sharma ◽  
Anoop Kumar
Keyword(s):  
Broad Spectrum ◽  
In Silico ◽  
Antibacterial Agent ◽  
Bacterial Infections ◽  
In Vitro Assays ◽  
Infection Model ◽  
Synergistic Activity ◽  
Bacterial Strains ◽  
Molecular Docking Study

Aim: The aim of the study was to find out the role of auranofin as a promising broad spectrum antibacterial agent. Methods: In-vitro assays (Percentage growth retardation, Bacterial growth kinetics, Biofilm formation assay) and In-silico study (Molegro virtual docker (MVD) version 6.0 and Molecular operating environment (MOE) version 2008.10 software). Results: The in vitro assays have shown that auranofin has good antibacterial activity against Gram positive and Gram negative bacterial strains. Further, auranofin has shown synergistic activity in combination with ampicillin against S. aureus and B. subtilis whereas in combination with neomycin has just shown additive effect against E. coli, P. aeruginosa and B. pumilus. In vivo results have revealed that auranofin alone and in combination with standard drugs significantly decreased the bioburden in zebrafish infection model as compared to control. The molecular docking study have shown good interaction of auranofin with penicillin binding protein (2Y2M), topoisomerase (3TTZ), UDP-3-O-[3- hydroxymyristoyl] N-acetylglucosaminedeacetylase (3UHM), cell adhesion protein (4QRK), β-lactamase (5CTN) and arylsulphatase (1HDH) enzyme as that of reference ligand which indicate multimodal mechanism of action of auranofin. Finally, MTT assay has shown non-cytotoxic effect of auranofin. Conclusion: In conclusion, auranofin in combination with existing antibiotics could be developed as a broad spectrum antibacterial agent; however, further studies are required to confirm its safety and efficacy. This study provides possibility of use of auranofin apart from its established therapeutic indication in combination with existing antibiotics to tackle the problem of resistance.

Mother Culture, Meet Mother Nature

2018 ◽  
Author(s):  
Luc Faucher ◽  
Pierre Poirier
Keyword(s):  
Evolutionary Algorithms ◽  
Cultural Change ◽  
Evolutionary Information ◽  
Multiple Forms ◽  
Human Immune System ◽  
Units Of Selection ◽  
Pluralistic Approach ◽  
Human Immune ◽  
Plausible Theory ◽  
Different Time Scales

Research on the adaptive characteristics of the human immune system reveals that evolutionary algorithms are not strictly matters of replication. And research in genomics suggests that there is no a single source of evolutionary information that carries the same content in every environment. A plausible theory of cultural evolution must acknowledge the possibility that multiple selective algorithms are operating at different time-scales, on different units of selection, with different logical structures; but it must explain how different selective processes are interfaced to yield culturally stable phenomena. This paper advances an empirically plausible approach to memetics that recognizes a wider variety of evolutionary algorithms; and it advances a pluralistic approach to cultural change. Finally, it shows that multiple forms of processing, operating at different timescales, on different units of selection, collectively sustain the human capacity to form and use certain types of representations.

scholarly journals Metabolic Swifts Govern Normal and Malignant B Cell Lymphopoiesis

2021 ◽  
Vol 22 (15) ◽  
pp. 8269
Author(s):  
Aikaterini Poulaki ◽  
Stavroula Giannouli
Keyword(s):  
B Cell ◽  
B Lymphocytes ◽  
Control Program ◽  
Memory B Cells ◽  
Immunologic Memory ◽  
Human Immune System ◽  
B Cell Malignancies ◽  
Stringent Control ◽  
Human Immune ◽  
New Research

B lymphocytes are an indispensable part of the human immune system. They are the effective mediators of adaptive immunity and memory. To accomplish specificity against an antigen, and to establish the related immunologic memory, B cells differentiate through a complicated and strenuous training program that is characterized by multiple drastic genomic modifications. In order to avoid malignant transformation, these events are tightly regulated by multiple checkpoints, the vast majority of them involving bioenergetic alterations. Despite this stringent control program, B cell malignancies are amongst the top ten most common worldwide. In an effort to better understand malignant pathobiology, in this review, we summarize the metabolic swifts that govern normal B cell lymphopoiesis. We also review the existent knowledge regarding malignant metabolism as a means to unravel new research goals and/or therapeutic targets.

scholarly journals Silver (I) N-Heterocyclic Carbene Complexes: A Winning and Broad Spectrum of Antimicrobial Properties

2021 ◽  
Vol 22 (5) ◽  
pp. 2497
Author(s):  
Filippo Prencipe ◽  
Anna Zanfardino ◽  
Michela Di Napoli ◽  
Filomena Rossi ◽  
Stefano D’Errico ◽  
...  
Keyword(s):  
Bacterial Infections ◽  
Antimicrobial Agents ◽  
Antimicrobial Properties ◽  
Resistance Mechanisms ◽  
Heterocyclic Carbenes ◽  
Significant Activity ◽  
Bacterial Strains ◽  
Development Of Resistance ◽  
Starting Point ◽  
Catalytic Chemistry

The evolution of antibacterial resistance has arisen as the main downside in fighting bacterial infections pushing researchers to develop novel, more potent and multimodal alternative drugs.Silver and its complexes have long been used as antimicrobial agents in medicine due to the lack of silver resistance and the effectiveness at low concentration as well as to their low toxicities compared to the most commonly used antibiotics. N-Heterocyclic Carbenes (NHCs) have been extensively employed to coordinate transition metals mainly for catalytic chemistry. However, more recently, NHC ligands have been applied as carrier molecules for metals in anticancer applications. In the present study we selected from literature two NHC-carbene based on acridinescaffoldand detailed nonclassicalpyrazole derived mono NHC-Ag neutral and bis NHC-Ag cationic complexes. Their inhibitor effect on bacterial strains Gram-negative and positivewas evaluated. Imidazolium NHC silver complex containing the acridine chromophore showed effectiveness at extremely low MIC values. Although pyrazole NHC silver complexes are less active than the acridine NHC-silver, they represent the first example of this class of compounds with antimicrobial properties. Moreover all complexesare not toxic and they show not significant activity againstmammalian cells (Hek lines) after 4 and 24 h. Based on our experimental evidence, we are confident that this promising class of complexes could represent a valuable starting point for developing candidates for the treatment of bacterial infections, delivering great effectiveness and avoiding the development of resistance mechanisms.

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