Immunomodulatory Activity of Various Fractions Derived from Physalis angulata L Extract

1992 ◽  
Vol 20 (03n04) ◽  
pp. 233-243 ◽  
Author(s):  
Yee-Shin Lin ◽  
Hsuch-Ching Chiang ◽  
Woei-Song Kan ◽  
Emily Hone ◽  
Shyh-Jen Shih ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
T Cells ◽  
Synergistic Effect ◽  
Antibody Responses ◽  
Immunomodulatory Activity ◽  
Moderate Activity ◽  
Immunomodulatory Effects ◽  
Slight Effect ◽  
Extract Fraction ◽  
Physalis Angulata

The immunomodulatory effects of Physalis angulata L. extract fraction VII (PA-VII), PA-VII-A, PA-VII-B and PA-VII-C were investigated in this study. The results showed that PA-VII and PA-VII-C strongly enhanced blastogenesis response, PA-VII-B had moderate activity, and PA-VII-A exerted only slight effect on cell proliferation. A synergistic effect was observed when the suboptimal dosage of phytohemagglutinin (PHA) or lipopolysaccharide (LPS) was added to the culture. Furthermore, PA-VII and PA-VII-C possessed stimulatory activity on B cells and less effect on T cells. The antibody responses were also augmented by PA-VII, PA-VII-B and PA-VII-C, but not by PA-VII-A. The enhancement of antibody response could be observed both in BALB/c and C3H/HeJ mice.

scholarly journals A screening strategy to identify novel immunomodulators

2021 ◽  
Author(s):  
◽  
Vimal Patel
Keyword(s):  
T Cells ◽  
Drug Discovery ◽  
Cytokine Production ◽  
Screening Strategy ◽  
Ease Of Use ◽  
Cluster Compounds ◽  
Immunomodulatory Activity ◽  
Immunomodulatory Effects ◽  
Data Set ◽  
Adaptive Immune Cells

<p>Understanding the immunomodulatory activities of compounds is important to identify the unintended adverse immunomodulatory effects of therapeutic compounds in development and to select novel compounds that may provide benefit for those diagnosed with immunemediated disorders. In both these cases, it is desirable to identify compounds with immunomodulatory activity early in the drug discovery process in a medium-throughput format. A screening strategy has been designed to fulfil these needs.  The first step in designing the strategy was to select informative assays and optimise individual assays to suit medium-throughput drug discovery. These individual assays investigated effects on a broad range of functions associated with innate and adaptive immune cells including macrophages (activation, cytokine production, phagocytosis and motility), helper T cells (activation and cytokine production), cytotoxic T cells (degranulation and cytokine production), and B cells (antibody production and cytokine production). Cost effectiveness and ease-of-use were important considerations during assay design and optimisation.  Using a compound set comprised of positive controls (i.e. compounds known to alter specific immune functions), a data set was generated to guide the strategy design. Assays were ordered to efficiently use resources and reduce the generation of less informative data. Additionally, using data collected from this compound set, strategies to assess and identify immunomodulatory activity were built and analysed. A second set of compounds was used to validate the screening strategy, and this screen highlighted new and novel activities for these known compounds that suggests they possess additional immunomodulatory effects.  Once validated, several novel compounds were run through the screen, including a traditional Samoan medicine, a heparan sulfate mimetic, and a novel anti-cancer agent; unique immunomodulatory activities were discovered. Finally, a hierarchical cluster analysis was used to cluster compounds sharing similar activity profiles and suggested the potential to develop further statistical methods to provide insight into compound characterisation. Together, this research has developed and validated a novel, medium throughput drug discovery system that can facilitate the identification of the immunomodulatory activities of compounds in the drug discovery environment.</p>

scholarly journals A screening strategy to identify novel immunomodulators

2021 ◽  
Author(s):  
◽  
Vimal Patel
Keyword(s):  
T Cells ◽  
Drug Discovery ◽  
Cytokine Production ◽  
Screening Strategy ◽  
Ease Of Use ◽  
Cluster Compounds ◽  
Immunomodulatory Activity ◽  
Immunomodulatory Effects ◽  
Data Set ◽  
Adaptive Immune Cells

<p>Understanding the immunomodulatory activities of compounds is important to identify the unintended adverse immunomodulatory effects of therapeutic compounds in development and to select novel compounds that may provide benefit for those diagnosed with immunemediated disorders. In both these cases, it is desirable to identify compounds with immunomodulatory activity early in the drug discovery process in a medium-throughput format. A screening strategy has been designed to fulfil these needs.  The first step in designing the strategy was to select informative assays and optimise individual assays to suit medium-throughput drug discovery. These individual assays investigated effects on a broad range of functions associated with innate and adaptive immune cells including macrophages (activation, cytokine production, phagocytosis and motility), helper T cells (activation and cytokine production), cytotoxic T cells (degranulation and cytokine production), and B cells (antibody production and cytokine production). Cost effectiveness and ease-of-use were important considerations during assay design and optimisation.  Using a compound set comprised of positive controls (i.e. compounds known to alter specific immune functions), a data set was generated to guide the strategy design. Assays were ordered to efficiently use resources and reduce the generation of less informative data. Additionally, using data collected from this compound set, strategies to assess and identify immunomodulatory activity were built and analysed. A second set of compounds was used to validate the screening strategy, and this screen highlighted new and novel activities for these known compounds that suggests they possess additional immunomodulatory effects.  Once validated, several novel compounds were run through the screen, including a traditional Samoan medicine, a heparan sulfate mimetic, and a novel anti-cancer agent; unique immunomodulatory activities were discovered. Finally, a hierarchical cluster analysis was used to cluster compounds sharing similar activity profiles and suggested the potential to develop further statistical methods to provide insight into compound characterisation. Together, this research has developed and validated a novel, medium throughput drug discovery system that can facilitate the identification of the immunomodulatory activities of compounds in the drug discovery environment.</p>

scholarly journals AB0345 Th9 CELLS AND THEIR ASSOCIATED CYTOKINES: THE PROBABLE PLAYERS IN SYSTEMIC LUPUS ERYTHEMATOSUS (SLE) AND TYPE 1 DIABETES MELLITUS (T1DM)

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1197.2-1198
Author(s):  
N. Mohannad ◽  
M. Moaaz ◽  
R. Mohamed Shehata
Keyword(s):  
T Cells ◽  
T Cell ◽  
Disease Activity ◽  
Clinical Manifestations ◽  
Moderate Activity ◽  
Healthy Controls ◽  
Group I ◽  
Pancreatic Islets Of Langerhans ◽  
Th9 Cells ◽  
Significant Difference

Background:SLE is an autoimmune disease (AID) of unknown origin. Several factors can contribute to immune dysfunction in SLE.Interleukin 9 (IL9) is a newly emerging T cell-derived factor preferentially expressed by CD4+T cells: T helper 9 (Th9)IL9 targets different cell lineages, and can contribute to the development of allergic & AIDsWhether abnormal expression and secretion of IL9 are present in SLE patients (pts) still unidentified. It is also unclear whether IL9 exerts main proinflammatory or anti-inflammatory activities in SLE. T1DM is characterized by inflammation of the pancreatic islets of Langerhans. Insulitis progresses over time and β cells become destroyed then clinical DM is established. T1DM is regarded as a T cell-driven AIDObjectives:Evaluation of the expression of CD4+ IL9+ T cells & the level of IL9 in SLE pts compared to both healthy subjects & pts with another AID: T1DM.Also, to evaluate the correlation of these expressions with clinical features, laboratory parameters and SLE activityMethods:The study included: Group I 25 SLE pts fulfilling SLICC classification criteria divided into 2 subgroups (gps) according to SLE disease activity index (SLEDAI) IA: 20 pts with mild to moderate activity (<12) IB:5 pts with severe activity (>12) recruited from rheumatology clinic or internal medicine ward (Rheumatology unit), Main University Hospital, Alexandria. Group II 15 healthy individuals as a first control gp. Group III 15 pts with T1DM fulfilling the American Diabetes Association criteria as a second control gp. All pts were subjected to history taking, clinical examination,laboratory investigations: CBC,LFT,KFT,ESR,CRP,ANA,Anti-dsDNA,Th9 cell expression detection by flowcytometry and serum IL9 by ELISAResults:There was no statistical difference between all gps as regards age & sex but a significant increased ESR in SLE compared to controls & T1DM p< 0.001 p=0.001Th9 expression was highly increased in SLE pts, range 0.13-4.54% & mean ±SD=1.50 ± 1.47% than both control gps. In healthy controls Th9 ranged between 0.0-1.29% with mean 0.37 ±0.52%, while in T1DM pts ranged between 0.03 to 2.13% with mean of 0.67 ± 0.59%. A high significant difference was found between SLE pts and controls p=0.001, an insignificant rise was seen in SLE pts compared to T1DM pts p=0.157. A high significant increase in Th9 was found in severe SLE: mean of 3.74 ±1.15% than in pts with mild to moderate SLE: mean 0.94±0.88% p=<0.001IL9 level was highly increased in SLE pts: mean of 42.83± 23.98 pg/ml than both control gps. In healthy controls the mean was 8.54±13.27, while in T1DM with mean of 29.17±16.09 pg/ml. A high significant difference was found between SLE pts and normal controls p<0.001 but an insignificant rise with T1DM p=0.294. A high significant increase in IL9 in pts with severe ds compared to mild to moderate pts p<0.001.A significant direct correlation between Th9 & IL9 and SLEDAI/105 A significant direct correlation between damage index and Th9 p=0.040 but not IL9 p=0.053In SLE no significant relation between Th9 or IL9 & clinical manifestations or disease duration. A direct correlations between Th9 & ESR p=0.046 and CRP p=0.025,a significant correlation between IL9 and CRP p=0.033, no correlations between Th9&IL9 level and anti-dsDNA p=0.593& 0.4 Significant direct correlation between Th9 and IL9 in T1DM pts, still no correlation with glycemic profile. IL9 levels were significantly increased in SLE with elevated CRP p=0.033 & the % of Th9 cells were increased with elevated ESR and CRP p=0.025, 0.046Conclusion:In SLE pts; IL9 level and Th9 cells expression were significantly elevated compared to healthy controls. IL9 levels and the percentages of Th9 directly correlated with the SLE disease activity. IL9 levels also were significantly increased in T1DM pts compared to controls,but they were less expressed than in SLE. This suggests an important role of IL9 in the pathogenesis AIDs as SLEReferences:[1]Tahernia L et al. Cytokines in SLE: their role in pathogenesis of disease and possible therapeutic opportunities. Rheum Res 2017Disclosure of Interests:None declared

Type D SRV‐2 virus‐specific CD8 + and CD4 ‐ CD8 ‐ T cells that regulate virus‐induced T cell proliferation in Celebes macaques

1993 ◽  
Vol 22 (2-3) ◽  
pp. 80-85
Author(s):  
A. Malley ◽  
N. Pangares ◽  
S.K. Mayo ◽  
M. Zeleny‐Pooley ◽  
J.V. Torres ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
T Cells ◽  
T Cell ◽  
Cd8 T Cells ◽  
T Cell Proliferation ◽  
Type D

scholarly journals Heterologous vaccination regimens with self-amplifying RNA and adenoviral COVID vaccines induce robust immune responses in mice

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Alexandra J. Spencer ◽  
Paul F. McKay ◽  
Sandra Belij-Rammerstorfer ◽  
Marta Ulaszewska ◽  
Cameron D. Bissett ◽  
...  
Keyword(s):  
Immune Response ◽  
Clinical Trials ◽  
T Cells ◽  
Immune Responses ◽  
Viral Vectors ◽  
Cytotoxic T Cells ◽  
Antibody Responses ◽  
Limited Data ◽  
Vectored Vaccine ◽  
Cellular Immune

AbstractSeveral vaccines have demonstrated efficacy against SARS-CoV-2 mediated disease, yet there is limited data on the immune response induced by heterologous vaccination regimens using alternate vaccine modalities. Here, we present a detailed description of the immune response, in mice, following vaccination with a self-amplifying RNA (saRNA) vaccine and an adenoviral vectored vaccine (ChAdOx1 nCoV-19/AZD1222) against SARS-CoV-2. We demonstrate that antibody responses are higher in two-dose heterologous vaccination regimens than single-dose regimens. Neutralising titres after heterologous prime-boost were at least comparable or higher than the titres measured after homologous prime boost vaccination with viral vectors. Importantly, the cellular immune response after a heterologous regimen is dominated by cytotoxic T cells and Th1+ CD4 T cells, which is superior to the response induced in homologous vaccination regimens in mice. These results underpin the need for clinical trials to investigate the immunogenicity of heterologous regimens with alternate vaccine technologies.

scholarly journals Packaging Covered with Antiviral and Antibacterial Coatings Based on ZnO Nanoparticles Supplemented with Geraniol and Carvacrol

2021 ◽  
Vol 22 (4) ◽  
pp. 1717
Author(s):  
Małgorzata Mizielińska ◽  
Paweł Nawrotek ◽  
Xymena Stachurska ◽  
Magdalena Ordon ◽  
Artur Bartkowiak
Keyword(s):  
Synergistic Effect ◽  
Moderate Activity ◽  
Gram Negative Bacteria ◽  
Human Pathogen ◽  
Safety Measures ◽  
Gram Negative ◽  
Airborne Viruses ◽  
Respiratory Droplets ◽  
Active Substances ◽  
External Coating

The purpose of the study was to obtain an external coating based on nanoparticles of ZnO, carvacrol, and geraniol that could be active against viruses such as SARS-Co-V2. Additionally, the synergistic effect of the chosen substances in coatings was analyzed. The goal of the study was to measure the possible antibacterial activity of the coatings obtained. Testing antiviral activity with human pathogen viruses, such as SARS-Co-V2, requires immense safety measures. Bacteriophages such as phi 6 phage represent good surrogates for the study of airborne viruses. The results of the study indicated that the ZC1 and ZG1 coatings containing an increased amount of geraniol or carvacrol and a very small amount of nanoZnO were found to be active against Gram-positive and Gram-negative bacteria. It is also important that a synergistic effect between these active substances was noted. This explains why polyethylene (PE) films covered with the ZC1 or ZG1 coatings (as internal coatings) were found to be the best packaging materials to extend the quality and freshness of food products. The same coatings may be used as the external coatings with antiviral properties. The ZC1 and ZG1 coatings showed moderate activity against the phi 6 phage that has been selected as a surrogate for viruses such as coronaviruses. It can be assumed that coatings ZG1 and ZC1 will also be active against SARS-CoV-2 that is transmitted via respiratory droplets.

scholarly journals Longitudinal analysis shows durable and broad immune memory after SARS-CoV-2 infection with persisting antibody responses and memory B and T cells

2021 ◽  
pp. 100354
Author(s):  
Kristen W. Cohen ◽  
Susanne L. Linderman ◽  
Zoe Moodie ◽  
Julie Czartoski ◽  
Lilin Lai ◽  
...  
Keyword(s):  
T Cells ◽  
Longitudinal Analysis ◽  
Antibody Responses ◽  
Immune Memory

scholarly journals Immunomodulatory effects of different intravenous immunoglobulin preparations in chronic lymphocytic leukemia

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ana Colado ◽  
Esteban Enrique Elías ◽  
Valeria Judith Sarapura Martínez ◽  
Gregorio Cordini ◽  
Pablo Morande ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cells ◽  
Chronic Lymphocytic Leukemia ◽  
T Cell Activation ◽  
Cell Activation ◽  
Lymphocytic Leukemia ◽  
Immunomodulatory Effects ◽  
Immunoglobulin Preparations

AbstractHypogammaglobulinemia is the most frequently observed immune defect in chronic lymphocytic leukemia (CLL). Although CLL patients usually have low serum levels of all isotypes (IgG, IgM and IgA), standard immunoglobulin (Ig) preparations for replacement therapy administrated to these patients contain more than 95% of IgG. Pentaglobin is an Ig preparation of intravenous application (IVIg) enriched with IgM and IgA (IVIgGMA), with the potential benefit to restore the Ig levels of all isotypes. Because IVIg preparations at high doses have well-documented anti-inflammatory and immunomodulatory effects, we aimed to evaluate the capacity of Pentaglobin and a standard IVIg preparation to affect leukemic and T cells from CLL patients. In contrast to standard IVIg, we found that IVIgGMA did not modify T cell activation and had a lower inhibitory effect on T cell proliferation. Regarding the activation of leukemic B cells through BCR, it was similarly reduced by both IVIgGMA and IVIgG. None of these IVIg preparations modified spontaneous apoptosis of T or leukemic B cells. However, the addition of IVIgGMA on in vitro cultures decreased the apoptosis of T cells induced by the BCL-2 inhibitor, venetoclax. Importantly, IVIgGMA did not impair venetoclax-induced apoptosis of leukemic B cells. Overall, our results add new data on the effects of different preparations of IVIg in CLL, and show that the IgM/IgA enriched preparation not only affects relevant mechanisms involved in CLL pathogenesis but also has a particular profile of immunomodulatory effects on T cells that deserves further investigation.

scholarly journals Costimulation by B7 Modulates Specificity of Cytotoxic T Lymphocytes: A Missing Link That Explains Some Bystander T Cell Activation

1997 ◽  
Vol 186 (10) ◽  
pp. 1787-1791 ◽  
Author(s):  
Pan Zheng ◽  
Yang Liu
Keyword(s):  
Cell Proliferation ◽  
T Cells ◽  
Influenza Virus ◽  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
T Cell Proliferation ◽  
Target Cells ◽  
Cell Proliferation And Differentiation ◽  
Proliferation And Differentiation

It has been proposed that some bystander T cell activation may in fact be due to T cell antigen receptor (TCR) cross-reactivity that is too low to be detected by the effector cytotoxic T lymphocyte (CTL). However, this hypothesis is not supported by direct evidence since no TCR ligand is known to induce T cell proliferation and differentiation without being recognized by the effector CTL. Here we report that transgenic T cells expressing a T cell receptor to influenza virus A/NT/68 nucleoprotein (NP) 366-374:Db complexes clonally expand and become effector CTLs in response to homologous peptides from either A/PR8/34 (H1N1), A/AA/60 (H2N2), or A/NT/68 (H3N2). However, the effector T cells induced by each of the three peptides kill target cells pulsed with NP peptides from the H3N2 and H2N2 viruses, but not from the H1N1 virus. Thus, NP366–374 from influenza virus H1N1 is the first TCR ligand that can induce T cell proliferation and differentiation without being recognized by CTLs. Since induction of T cell proliferation was mediated by antigen-presenting cells that express costimulatory molecules such as B7, we investigated if cytolysis of H1N1 NP peptide–pulsed targets can be restored by expressing B7-1 on the target cells. Our results revealed that this is the case. These data demonstrated that costimulatory molecule B7 modulates antigen specificity of CTLs, and provides a missing link that explains some of the bystander T cell activation.

scholarly journals CD4+ CD25+ Regulatory T Cells Modulate the T-Cell and Antibody Responses in Helicobacter-Infected BALB/c Mice

2006 ◽  
Vol 74 (6) ◽  
pp. 3519-3529 ◽  
Author(s):  
Maria Kaparakis ◽  
Karen L. Laurie ◽  
Odilia Wijburg ◽  
John Pedersen ◽  
Martin Pearse ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Bacterial Colonization ◽  
Antibody Responses ◽  
T Helper 1 ◽  
Time Of Infection ◽  
Lymph Node Cells ◽  
Antibody Levels ◽  
And Control

ABSTRACT Gastric Helicobacter spp. induce chronic gastritis that may lead to ulceration and dysplasia. The host elicits a T helper 1 (Th1) response that is fundamental to the pathogenesis of these bacteria. We analyzed immune responses in Helicobacter-infected, normal mice depleted of CD4+ CD25+ T cells to investigate the in vivo role of regulatory T cells (Tregs) in the modulation of Helicobacter immunopathology. BALB/c and transgenic mice were depleted of CD4+ CD25+ T cells by administration of an anti-CD25 antibody either at the time of infection with Helicobacter or during chronic infection and gastritis. Depletion of CD25+ Tregs prior to and during infection of mice with Helicobacter spp. did not affect either bacterial colonization or severity of gastritis. Depletion of CD25+ Tregs was associated with increased Helicobacter-specific antibody levels and an altered isotype distribution. Paragastric lymph node cells from CD25+ Treg-depleted and control infected mice showed similar proliferation to Helicobacter antigens, but only cells from anti-CD25-treated animals secreted Th2 cytokines. CD25+ Tregs do not control the level of gastritis induced by gastric Helicobacter spp. in normal, thymus-intact BALB/c mice. However, CD25+ Tregs influence the cytokine and antibody responses induced by infection. Autoimmune gastritis is not induced in Helicobacter-infected mice depleted of CD25+ Tregs but is induced in CD25+ Treg-depleted mice, which have a higher frequency of autoreactive T cells.

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