Search Results (4)

Mathematical models are becoming indispensable tools to explore the complexities of biological systems at cellular levels. We present a model to explore the baseline immune cell interactions for in vitro polyclonal antibody synthesis via B-cells regulated by helper and regulatory T-cells. The model incorporates interactions of antigen-presenting cells, T-cells, regulatory T-cells, and B-cells with each other and predicts time-dependent trajectories of these cells and antibody synthesis stimulated by pokeweed mitogen. We used an ordinary differential equation-based approach to simulate the dynamic changes in the cells and cytokines numbers due to the cellular and humoral response to pokeweed mitogen stimulation. The parameters of the ordinary differential equations model are determined to yield a normal immune response as observed in the pokeweed mitogen-stimulated in vitro antibody synthesis via normal T, B, and antigen-presenting cells. The dose effects of antigen load and basal values of regulatory T-cells on the profiles of various immune response variables are also evaluated. Full article

Oedema disease (OD) in piglets is one of the most important pathologies, as it causes significant losses due to the high mortality because of the Shiga toxin family, which produces Escherichia coli (STEC) strains. The main toxin responsible for the characteristic pathologies in pigs is Shiga toxin 2 subtype e (Stx2e). Moreover, there is growing evidence that Stx’s family of toxins also targets immune cells. Therefore, this study evaluated the effect of different concentrations of Stx2e on porcine immune cells. Porcine peripheral blood mononuclear cells were pre-incubated with Stx2e, at three different concentrations (final concentrations of 10, 500, and 5000 CD50/mL) and with a negative control group. Cells were then stimulated with polyclonal mitogens: concanavalin A, phytohemagglutinin, pokeweed mitogen, or lipopolysaccharides. Cell proliferation was assessed by BrdU (or EdU) incorporation into newly created DNA. The activation of the lymphocyte subsets was assessed by the detection of CD25, using flow cytometry. The toxin significantly decreased mitogen-driven proliferation activity, and the effect was partially dose-dependent, with a significant impact on both T and B populations. The percentage of CD25+ cells was slightly lower in the presence of Stx2e in all the defined T cell subpopulations (CD4+, CD8+, and γδTCR+)—in a dose-dependent manner. B cells seemed to be the most affected populations. The negative effects of different concentrations of Stx2e on the immune cells in this study may explain the negative impact of the subclinical course of OD. Full article

We recently identified a deviant bovine immune phenotype characterized by hyperproliferation of lymphocytes after polyclonal stimulation. This phenotype was first discovered in dams that responded to PregSure BVD vaccination by producing pathological antibodies, triggering the fatal disease “bovine neonatal pancytopenia” in calves. The aim of the study was to gain deeper insights into molecular processes occurring in lymphocytes of immune phenotypes and the effect on their secretome after immune stimulation. Two discovery proteomic experiments were performed with unstimulated and Pokeweed Mitogen (PWM) stimulated lymphocytes, using label-free LC-MS/MS. In lymphocytes, 2447 proteins were quantified, and 1204 proteins were quantified in the secretome. Quantitative proteome analysis of immune deviant and control samples after PWM stimulation revealed clear differences. The increase in abundance of IL17A, IL17F, IL8, CCL5, LRRC59, and CLIC4 was higher in controls through mitogenic stimulation. In contrast, the abundance of IFNγ, IL2, IL2RA, CD83, and CD200 increased significantly more in immune deviant lymphocytes. Additional pathway enrichment analysis of differentially secreted proteins also yielded fundamental differences between the immune phenotypes. Our study provides a comprehensive dataset, which gives novel insights into proteome changes of lymphocytes from different bovine immune phenotypes. These differences point to the development of diverse immune responses of bovine immune phenotypes after immune stimulation. Full article

Oxidative stress is implicated in HIV-infection. It has been suggested that plant antioxidants may offer protection from viral replication and cell death associated with oxidative stress in patients with HIV/AIDS. Because of inherent antioxidant properties of turmeric (T) and its derivatives, water-soluble extract turmerin (Tm) and lipid soluble curcumin (Cu), their potential efficacy as anti-HIV drugs were examined. Cell viability and p-24 antigen release by CEMss-T cells (1 x 10⁵ cells/ml) infected with HIV-III_B strain, used as an acute model of infection, were tested in the presence of 3’azido-3’deoxythmidine (AZT). Proliferative responses of human mononuclear cells derived from HIV patients (chronic model) stimulated with phyohemagglutinin (PHA), concanavalin A (ConA), and pokeweed mitogen (PWM) were also examined in the presence of AZT and Tm. In the infection assay, T, Tm and Cu individually did not reduce p-24 antigen release or improve cell viability. AZT (5μM) + Tm (800 ng/ml) inhibited infection by 37 % and increased cell numbers by 30%; whereas, Tm (80 ng/ml) inhibited infection by 26% and increased cell number by 60%. In the proliferation assay, lymphocytes from HIV-infected patients showed better inhibition of mitogen responsiveness to Tm (800 ng/ml) when compared to AZT at 5 μM or Tm at 80 ng/ml. Turmerin inhibited HIV-infected T-cell proliferation and, in combination with AZT, decreased T-cell infection and increased cell viability. These data provide evidence suggesting that efficacious anti-HIV therapy may be possible using lower, less toxic doses of AZT in the presence of turmerin. Full article