scholarly journals Computational investigations of the immune response to repeated influenza infections and vaccinations

2021 ◽  
Vol 8 (3) ◽  
Author(s):  
Emmanuel S. Adabor
Keyword(s):  
Immune Response ◽  
Immune Cells ◽  
Computational Analysis ◽  
T Regulatory Cells ◽  
Influenza Season ◽  
Influenza Viruses ◽  
Antibody Responses ◽  
Regulatory Cells ◽  
Subsequent Infection ◽  
Susceptibility To Infection

Previous studies have shown that repeated influenza vaccination can enhance susceptibility to subsequent infection with a drifted influenza virus strain. This paper seeks to further understanding of the interactions between influenza viruses and specific immune cells that accompany this phenomenon. The paper argues that repeated vaccination increases susceptibility to infection only in the context of a residual immunity induced by prior vaccination or infection. The results of computational analysis indicate that this is a dynamic consequence of interactions between vaccines, influenza viruses and specific immune cells. In particular, mathematical modelling was used to show that in the presence of residual immunity conferred by a vaccine administered in Canada in the 2013–2014 influenza season, the 2014–2015 season vaccine enhanced susceptibility to infection. Such infection enhancement occurs when the 2014–2015 vaccine boosts suppressive T-regulatory cells induced by the 2013–2014 vaccine, decreasing the strength of antibody responses to the infecting strain. Overall, the study suggests probable characteristics of infecting viruses and vaccines that make repeated influenza infections and vaccinations detrimental.

Abstract 13073: Epicardial YAP/TAZ Regulate an Immune Suppressive Response Following Myocardial Infarction

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Vimal Ramjee ◽  
Manvendra K Singh ◽  
Feiyan Liu ◽  
Kurt A Engleka ◽  
Lauren J Manderfield ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Immune Response ◽  
T Cells ◽  
Heart Disease ◽  
T Regulatory Cells ◽  
Hippo Signaling ◽  
Regulatory Cells ◽  
Strong Immune Response ◽  
Inflammation Response ◽  
Injured Myocardium

Ischemic heart disease constitutes the most prevalent type of heart disease in the US. Remodeling post-myocardial infarction (MI) is a multifaceted process driven by a strong immune response. Regulatory T-cells, a subset of CD4+ T-cells, have been shown to suppress the innate and adaptive immune response following myocardial injury to allow for less deleterious remodeling. To date, the precise mechanism by which injured myocardium recruits these suppressive immune cells remains unknown. Here, we show a novel role for the epicardium in suppressing the post-infarct inflammation response through recruitment of T-regulatory cells. The Hippo pathway is a signal transduction pathway, which has gained importance in determining organ size and is implicated as a critical regulator of tissue regeneration. Mice deficient in epicardial YAP/TAZ, two core effectors of the Hippo signaling pathway, develop profound pericardial inflammation, thoracic adhesions and myocardial fibrosis post-MI, with resultant cardiomyopathy and death. These mice demonstrate fewer suppressive T-regulatory cells in the injured myocardium, due to a deficiency of interferon-gamma, a known inducer of these T-cells. Collectively, these results suggest a novel role for Hippo signaling in immune regulation. In addition, our data suggest that the epicardium plays an important role in homing suppressive T-regulatory cells to injured myocardium so that the inflammation response may be attenuated following MI.

Unraveling the immune response during AIHA

Blood ◽  
2008 ◽  
Vol 111 (2) ◽  
pp. 483-483
Author(s):  
Neil D. Avent
Keyword(s):  
Immune Response ◽  
Autoimmune Disease ◽  
Hemolytic Anemia ◽  
Autoimmune Hemolytic Anemia ◽  
T Regulatory Cells ◽  
Regulatory Cells

In this issue of Blood, Ward and colleagues make some novel fundamental observations on the nature of the immune response during autoimmune hemolytic anemia (AIHA). They show a key role for T regulatory cells (Tregs) in the pathogenesis of this autoimmune disease.

scholarly journals A Multi-Phenotype System to Discover Therapies for Age-Related Dysregulation of the Immune Response to Viral Infections

2020 ◽  
Author(s):  
Brandon White ◽  
Ben Komalo ◽  
Lauren Nicolaisen ◽  
Matt Donne ◽  
Charlie Marsh ◽  
...  
Keyword(s):  
Older Adults ◽  
Immune Response ◽  
Viral Infection ◽  
Immune Cells ◽  
Viral Infections ◽  
Cell Interaction ◽  
Rapid Identification ◽  
Beneficial Effects ◽  
Susceptibility To Infection ◽  
Age Related

ABSTRACTAge-related immune dysregulation contributes to increased susceptibility to infection and disease in older adults. We combined high-throughput laboratory automation with machine learning to build a multi-phenotype aging profile that models the dysfunctional immune response to viral infection in older adults. From a single well, our multi-phenotype aging profile can capture changes in cell composition, physical cell-to-cell interaction, organelle structure, cytokines, and other hidden complexities contributing to age-related dysfunction. This system allows for rapid identification of new potential compounds to rejuvenate older adults’ immune response. We used our technology to screen thousands of compounds for their ability to make old immune cells respond to viral infection like young immune cells. We observed beneficial effects of multiple compounds, of which two of the most promising were disulfiram and triptonide. Our findings indicate that disulfiram could be considered as a treatment for severe coronavirus disease 2019 and other inflammatory infections.

The Frequency of T Regulatory Cells Modulates the Survival of Multiple Myeloma Patients: Detailed Characterization of Immune Status In Multiple Myeloma

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 984-984
Author(s):  
Krzysztof Giannopoulos ◽  
Wioletta Kaminska ◽  
Anna Dmoszynska
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Immune System ◽  
Dendritic Cell ◽  
Immune Cells ◽  
T Regulatory Cells ◽  
Control Group ◽  
Regulatory Cells ◽  
Cell Antigen ◽  
Blood Dendritic Cell

Abstract Abstract 984 Multiple myeloma (MM) is a immunoproliferative disease which is characterized by the uncontrolled proliferation of plasma cells which is accompanied by defects in the immune system. Abnormalities of function and number of T regulatory cells (Treg), dendritic cells (DC) might be responsible for the immunosuppression in MM. DC and Treg are the most important cells in the immune system, able to control peripheral tolerance as well as response to foreign and tumor antigens. The current study aimed to characterize the frequency of Treg, DC as well as subpopulations of T cells bearing regulatory properties like CD4+GITR+, CD4+CD62L+, CD3+TCRγδ+ along with the concentration of IL-10, TGFβ, IL-6 in patients with MM. Subsequently the influence of therapy on those components of immune system was assessed. The study population consisted of 66 newly diagnosed MM patients (females-29, males-37, median age 66.5 years; range 39–81) admitted to the Department of Hematoonocology Medical University of Lublin. The study was approved by the Local Ethics Committee. Immune cells subpopulations were evaluated by the flow cytometry. Myeloid DC (MDC) were identified as blood dendritic cell antigen-1 (BDCA-1) positive and CD19 negative cells. Plasmacytoid DC (PDC) were characterized as blood dendritic cell antigen-1 (BDCA-2) and CD123 positive cells. We also estimated the frequency of Treg (CD4+CD25hiFOXP3+) and other populations of lymphocytes with regulatory function such as: CD4+GITR+, CD4+CD62L+, CD3+TCRγδ+. We used enzyme linked (ELISA) assay to detect cytokines IL-10, IL-6, TGFβ in serum of MM patients. In the current study we observed that the percentage of both MDC and PDC was lower in MM compared to control group (0.16% vs. 0.19% and 0.03% vs. 0.12%, respectively). The frequency of Treg was significantly higher in MM patients compared to healthy control (6.16% vs 0.05%). Also, the percentages of CD4+GITR+, CD4+CD62L+ were increased compared to healthy volunteers (95.19% vs 78% and 10.35% vs 0.42%, respectively). The frequency of CD3+TCRγδ+ was lower compared to control group (2.82% vs 6.05%). We further assessed the influence of certain immune cells frequencies on clinical behavior of MM patients. We found that patients with higher percentages of Treg live shorter (median survival 21 months vs not-reached, p=0.013, Figure 1). Serum levels of cytokines IL-10, IL-6, TGFβ were increased in MM compared to control group (1.16pg/mL vs 0.91pg/mL for IL-10; 3.74pg/mL vs 2.12pg/mL for IL-6; 32233.5pg/mL vs 3877.23pg/mL for TGFβ). During therapy we detected significant lowering concentration of IL-10, to higher extent in responders. In conclusion our results identified several abnormalities of immune system in MM. The dysfunction of immune system (decreased antigen presentation along with increased frequencies of suppressive cells and cytokines) might facilitate progression of the disease and infectious complications. The most important finding of our study is the key function of Treg in modulation of overall survival of MM patients. Overall survival by low (Treg low – below the median) and high (Treg hi – above the median) T regulatory cells frequencies of multiple myeloma patients. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Contemporary H3N2 influenza viruses have a glycosylation site that alters binding of antibodies elicited by egg-adapted vaccine strains

2017 ◽  
Vol 114 (47) ◽  
pp. 12578-12583 ◽  
Author(s):  
Seth J. Zost ◽  
Kaela Parkhouse ◽  
Megan E. Gumina ◽  
Kangchon Kim ◽  
Sebastian Diaz Perez ◽  
...  
Keyword(s):  
Seasonal Influenza ◽  
Influenza Season ◽  
Antigenic Site ◽  
Glycosylation Site ◽  
Influenza Viruses ◽  
Antibody Responses ◽  
H3n2 Virus ◽  
Viral Strain ◽  
H3n2 Influenza ◽  
H3n2 Vaccine

H3N2 viruses continuously acquire mutations in the hemagglutinin (HA) glycoprotein that abrogate binding of human antibodies. During the 2014–2015 influenza season, clade 3C.2a H3N2 viruses possessing a new predicted glycosylation site in antigenic site B of HA emerged, and these viruses remain prevalent today. The 2016–2017 seasonal influenza vaccine was updated to include a clade 3C.2a H3N2 strain; however, the egg-adapted version of this viral strain lacks the new putative glycosylation site. Here, we biochemically demonstrate that the HA antigenic site B of circulating clade 3C.2a viruses is glycosylated. We show that antibodies elicited in ferrets and humans exposed to the egg-adapted 2016–2017 H3N2 vaccine strain poorly neutralize a glycosylated clade 3C.2a H3N2 virus. Importantly, antibodies elicited in ferrets infected with the current circulating H3N2 viral strain (that possesses the glycosylation site) and humans vaccinated with baculovirus-expressed H3 antigens (that possess the glycosylation site motif) were able to efficiently recognize a glycosylated clade 3C.2a H3N2 virus. We propose that differences in glycosylation between H3N2 egg-adapted vaccines and circulating strains likely contributed to reduced vaccine effectiveness during the 2016–2017 influenza season. Furthermore, our data suggest that influenza virus antigens prepared via systems not reliant on egg adaptations are more likely to elicit protective antibody responses that are not affected by glycosylation of antigenic site B of H3N2 HA.

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