scholarly journals Febrile temperatures increase in vitro antibody affinity for malaria and dengue antigens

2018 ◽  
Author(s):  
Razvan C. Stan ◽  
Katia S. Françoso ◽  
Rubens P.S. Alves ◽  
Luís Carlos S. Ferreira ◽  
Irene S. Soares ◽  
...  
Keyword(s):  
Immune Responses ◽  
Binding Affinity ◽  
The Body ◽  
Antibody Affinity ◽  
Positive Role ◽  
Protein Partners ◽  
Adaptive Role

AbstractFever is a regulated elevation in the body setpoint temperature and may arise as a result of infectious and noninfectious causes. While beneficial in modulating immune responses to infection, the potential of febrile temperatures in regulating antigen binding affinity to antibodies has not been explored. We have investigated this process under in vitro conditions using selected malaria or dengue antigens and specific monoclonal antibodies, and observed a marked increase in the affinity of these antibody-antigen complexes at 40°C, compared to physiological (37°C) or pathophysiological temperatures (42°C). Induced thermal equilibration of the protein partners at these temperatures, prior to measurements, further increased their binding affinity. These results may indicate an unexpected beneficial and adaptive role for fever in vivo, and highlight the positive role of thermal priming in enhancing protein-protein affinity for samples of scarce availability.

The Role of Polyphenols in the Modulation of Plasma Non-Enzymatic Antioxidant Capacity (NEAC)

2012 ◽  
Vol 82 (3) ◽  
pp. 228-232 ◽  
Author(s):  
Mauro Serafini ◽  
Giuseppa Morabito
Keyword(s):  
Antioxidant Capacity ◽  
Dietary Intervention ◽  
Ex Vivo ◽  
The Body ◽  
Dietary Polyphenols ◽  
Enzymatic Antioxidant ◽  
Endogenous Antioxidant

Dietary polyphenols have been shown to scavenge free radicals, modulating cellular redox transcription factors in different in vitro and ex vivo models. Dietary intervention studies have shown that consumption of plant foods modulates plasma Non-Enzymatic Antioxidant Capacity (NEAC), a biomarker of the endogenous antioxidant network, in human subjects. However, the identification of the molecules responsible for this effect are yet to be obtained and evidences of an antioxidant in vivo action of polyphenols are conflicting. There is a clear discrepancy between polyphenols (PP) concentration in body fluids and the extent of increase of plasma NEAC. The low degree of absorption and the extensive metabolism of PP within the body have raised questions about their contribution to the endogenous antioxidant network. This work will discuss the role of polyphenols from galenic preparation, food extracts, and selected dietary sources as modulators of plasma NEAC in humans.

scholarly journals Role of Type I Interferons on Filovirus Pathogenesis

Vaccines ◽  
2019 ◽  
Vol 7 (1) ◽  
pp. 22 ◽  
Author(s):  
Beatriz Escudero-Pérez ◽  
César Muñoz-Fontela
Keyword(s):  
Animal Models ◽  
Immune Responses ◽  
Marburg Virus ◽  
Type I Interferons ◽  
Type I ◽  
Adaptive Immune ◽  
Antigen Presenting

Filoviruses, such as Ebola and Marburg virus, encode viral proteins with the ability to counteract the type I interferon (IFN-I) response. These IFN-I antagonist proteins are crucial to ensure virus replication, prevent an antiviral state in infected and bystander cells, and impair the ability of antigen-presenting cells to initiate adaptive immune responses. However, in recent years, a number of studies have underscored the conflicting data between in vitro studies and in vivo data obtained in animal models and clinical studies during outbreaks. This review aims to summarize these data and to discuss the relative contributions of IFN-α and IFN-β to filovirus pathogenesis in animal models and humans. Finally, we evaluate the putative utilization of IFN-I in post-exposure therapy and its implications as a biomarker of vaccine efficacy.

scholarly journals The Generation and Regulation of Tissue-Resident Tregs and Their Role in Autoimmune Diseases

2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Shuang Wang ◽  
Xueyang Zou ◽  
Yi Zhang ◽  
Xiaoya Wang ◽  
Wei Yang ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
T Cells ◽  
Immune Responses ◽  
Autoimmune Diseases ◽  
Hot Spot ◽  
Exploratory Stage ◽  
And Function

Regulatory T cells (Tregs), as an important subset of T cells, play an important role in maintaining body homeostasis by regulating immune responses and preventing autoimmune diseases. In-depth research finds that Tregs have strong instability and plasticity, and according to their developmental origin, Tregs can be classified into thymic-derived Tregs (tTregs), endogenous-induced Tregs (pTregs), which are produced by antigen-stimulated T cells in the periphery in vivo, and induced Tregs (iTregs), which differentiate from naïve T cells in vitro. In recent years, studies have found that Tregs are divided into lymphatic and tissue-resident Tregs according to their location. Research on the generation and function of lymphoid Tregs has been more comprehensive and thorough, but the role of tissue Tregs is still in the exploratory stage, and it has become a research hot spot. In this review, we discuss the instability and plasticity of Tregs and the latest developments of tissue-resident Tregs in the field of biology, including adipose tissue, colon, skeletal muscle, and other Tregs that have been recently discovered as well as their production, regulation, and function in specific tissues and their role in the pathogenesis of autoimmune diseases.

EXTH-21. MECHANISMS OF SYNERGISTIC GROWTH SUPPRESSION BY RADIOTHERAPY AND C-MET INHIBITION IN EXPERIMENTAL GLIOBLASTOMA

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi167-vi168
Author(s):  
Manuela Silginer ◽  
Eleanna Papa ◽  
Emese Szabo ◽  
Flavio Vasella ◽  
Patrick Roth ◽  
...  
Keyword(s):  
Immune Responses ◽  
Synergistic Effects ◽  
Glioma Cells ◽  
Immunodeficient Mice ◽  
Glioma Growth ◽  
Pathway Inhibition ◽  
Murine Glioma

Abstract Glioblastoma remains to be one of the most lethal solid cancers and novel therapies are urgently needed. There is increasing interest in the role of the HGF/MET pathway in the response of glioblastoma to radiotherapy. c-MET-mediated radioresistance may be partially induced via proinvasive and DNA damageresponse pathways and HGF may be involved in the regulation of immune responses. Here, we explored the role of the c-MET pathway in response to radiotherapy and investigated potential modes of action that mediate synergistic effects of MET pathway inhibition and irradiation in syngeneic murine glioma models in vitro and in vivo. Murine glioma cells express HGF and c-MET and respond with c-MET phosphorylation upon exposure to exogenous HGF. In vitro, glioma cell viability and proliferation are not affected by pharmacological or genetic c-MET pathway interference, and the c-MET inhibitor tepotinib fails to sensitize glioma cells to irradiation. Conversely, in vivo c-MET inhibition combined with focal radiotherapy synergistically prolongs survival in two syngeneic orthotopic glioma models compared with either treatment alone. Complementary studies demonstrated that synergy was lost when gliomas were established and treated in immunodeficient mice, and importantly, also when c-MET gene expression was disrupted in the tumor. Thus, synergistic suppression of experimental syngeneic glioma growth by irradiation and c-MET inhibition requires at least two mechanisms, expression of c-MET in the tumor and a functional immune system. In summary, our data suggest clinical evaluation of c-MET pathway inhibition in combination with radiotherapy in human glioblastoma.

in vivo and in vitro analysis of the functional role of Epstein-Barr virus-induced gene 3 (EBI3) for regulation of Th2 mediated immune responses

2003 ◽  
Vol 124 (4) ◽  
pp. A335
Author(s):  
Stefan J. Wirtz ◽  
Christoph Becker ◽  
Edward E.S. Nieuwenhuis ◽  
Mark Birkenbach ◽  
Richard S. Blumberg ◽  
...  
Keyword(s):  
Immune Responses ◽  
Functional Role ◽  
Epstein Barr Virus ◽  
Barr Virus ◽  
Epstein Barr ◽  
Vitro Analysis ◽  
In Vitro Analysis

scholarly journals The role of the angiotensins in the pathogenesis of inflammatory joint disease

2021 ◽  
Vol 93 (5) ◽  
pp. 635-639
Author(s):  
Andrei V. Gordeev ◽  
Elena A. Galushko ◽  
Natalia M. Savushkina
Keyword(s):  
Cardiovascular System ◽  
The Body ◽  
Joint Disease ◽  
Renin Angiotensin Aldosterone System ◽  
Renin Angiotensin ◽  
In Vivo Experiments ◽  
Anti Inflammatory

The significant humoral effect of the renin-angiotensin-aldosterone system on the regulation of the cardiovascular system and blood pressure has long been widely known. However, the identification and interpretation of new components of renin-angiotensin-aldosterone system in recent years can significantly expand the range of its potential effects on the body. The anti-inflammatory effect of drugs that block angiotensin II and its receptors, including in rheumatic diseases, can become practically significant for General therapists by their effect on reducing the concentration of inflammatory mediators and angiogenesis processes. The organoprotective and anti-inflammatory potentials of drugs that reduce the production of at demonstrated in vitro and in vivo experiments allow us to consider them as first-line angiotropic agents in patients with rheumatoid arthritis, especially in the presence of pathology of the cardiovascular system and kidneys.

Immunological and pathological responses in BALB/c mice induced by genetic administration ofTc13 Tul antigen ofTrypanosoma cruzi

Parasitology ◽  
2006 ◽  
Vol 132 (6) ◽  
pp. 855-866 ◽  
Author(s):  
G. A. GARCÍA ◽  
M. R. ARNAIZ ◽  
S. A. LAUCELLA ◽  
M. I. ESTEVA ◽  
N. AINCIART ◽  
...  
Keyword(s):  
Immune Responses ◽  
Dna Encoding ◽  
Genetic Immunization ◽  
Humoral Immune ◽  
Specific Memory ◽  
Family Protein ◽  
Ifn Γ

Tc13 is atrans-sialidase family protein ofTrypanosoma cruzi, the aetiological agent of Chagas' disease. Recently,in vitrostudies had suggested thatTc13 might participate in the pathogenesis of the disease. In order to study the role ofTc13 antigens in anin vivomodel, we administered plasmid DNA encoding aTc13 antigen from the Tulahuén strain (Tc13 Tul) to BALB/c mice and evaluated the immunological and pathological manifestations as well as the capacity of this antigen to confer protection againstT. cruziinfection.Tc13 Tul immunization did not elicit a detectable humoral immune response but induced specific memory T-cells with no capacity to produce IFN-γ. Five months after DNA-immunization withTc13 Tul, signs of hepatotoxicity and reactive changes in the heart, liver and spleen were observed in 40–80% of mice. WhenTc13 Tul DNA-immunized animals were challenged with trypomastigotes, a significant decrease in parasitaemia in early and late acute phase was observed without modification in the survival rate. Surprisingly,Tc13 Tul-immunized mice chronically infected withT. cruzishowed a decrease in the severity of heart damage. We conclude that, in BALB/c mice, genetic immunization withTc13 Tul mainly induces immune responses associated with pathology.

scholarly journals How does the NPM1 mutant induce leukemia?

2011 ◽  
Vol 3 (2s) ◽  
pp. 6 ◽  
Author(s):  
Paolo Sportoletti
Keyword(s):  
Myeloid Leukemia ◽  
Tumor Development ◽  
Genetic Alterations ◽  
In Vivo Studies ◽  
Npm1 Mutation ◽  
Protein Partners ◽  
Cellular Pathways

NPM1 is the most frequently mutated gene in AML and the role of the NPM1 mutant in acute myeloid leukemia along with its leukemogenic potential are still under investigation. NPM1 genetic alterations can contribute to leukemogenesis through the direct oncogenic effect of the mutant protein and the concomitant loss of one functional allele. Npm1 loss determines tumor development in the mouse while in human NPM1 maps in a chromosomal region frequently loss in myelodysplastic syndrome (MDS). The NPM1 mutant cytoplasmic delocalization in leukemic blasts alters multiple cellular pathways through either loss or gain of function effects on different protein partners. Here we discuss the most relevant studies on the role of the NPM1 molecule in hematological malignancies and both in vitro and in vivo studies that are trying to elucidate the way by which the NPM1 mutation induces leukemia.

Flagellar microtubule doublet assembly in vitro reveals a regulatory role of tubulin C-terminal tails

Science ◽  
2019 ◽  
Vol 363 (6424) ◽  
pp. 285-288 ◽  
Author(s):  
M. Schmidt-Cernohorska ◽  
I. Zhernov ◽  
E. Steib ◽  
M. Le Guennec ◽  
R. Achek ◽  
...  
Keyword(s):  
Intraflagellar Transport ◽  
Structural Basis ◽  
Ciliary Beating ◽  
Protein Partners ◽  
A Cell ◽  
Carboxyl Terminal ◽  
Microtubule Doublet

Microtubule doublets (MTDs), consisting of an incomplete B-microtubule at the surface of a complete A-microtubule, provide a structural scaffold mediating intraflagellar transport and ciliary beating. Despite the fundamental role of MTDs, the molecular mechanism governing their formation is unknown. We used a cell-free assay to demonstrate a crucial inhibitory role of the carboxyl-terminal (C-terminal) tail of tubulin in MTD assembly. Removal of the C-terminal tail of an assembled A-microtubule allowed for the nucleation of a B-microtubule on its surface. C-terminal tails of only one A-microtubule protofilament inhibited this side-to-surface tubulin interaction, which would be overcome in vivo with binding protein partners. The dynamics of B-microtubule nucleation and its distinctive isotropic elongation was elucidated by using live imaging. Thus, inherent interaction properties of tubulin provide a structural basis driving flagellar MTD assembly.

scholarly journals Potential Roles and Functions of Listerial Virulence Factors during Brain Entry

Toxins ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 297
Author(s):  
Franjo Banović ◽  
Horst Schroten ◽  
Christian Schwerk
Keyword(s):  
Virulence Factors ◽  
Current Knowledge ◽  
Cellular Adhesion ◽  
The Body ◽  
Listeriolysin O ◽  
The Brain ◽  
Adhesion And Invasion

Although it rarely induces disease in humans, Listeria monocytogenes (Lm) is important due to the frequency of serious pathological conditions—such as sepsis and meningitis—it causes in those few people that do get infected. Virulence factors (VF) of Lm—especially those involved in the passage through multiple cellular barriers of the body, including internalin (Inl) family members and listeriolysin O (LLO)—have been investigated both in vitro and in vivo, but the majority of work was focused on the mechanisms utilized during penetration of the gut and fetoplacental barriers. The role of listerial VF during entry into other organs remain as only partially solved puzzles. Here, we review the current knowledge on the entry of Lm into one of its more significant destinations, the brain, with a specific focus on the role of various VF in cellular adhesion and invasion.

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