Influenza vaccination is a common approach to prevent seasonal and pandemic influenza. Pre-existing antibodies against close viral strains might impair antibody formation against previously unseen strains–a process called original antigenic sin. The role of this pre-existing cellular immunity in this process is, despite some hints from animal models, not clear. Here, we analyzed cellular and humoral immunity in healthy individuals before and after vaccination with seasonal influenza vaccine. Based on influenza-specific hemagglutination inhibiting (HI) titers, vaccinees were grouped into HI-negative and -positive cohorts followed by in-depth cytometric and TCR repertoire analysis. Both serological groups revealed cross-reactive T-cell memory to the vaccine strains at baseline that gave rise to the majority of vaccine-specific T-cells post vaccination. On the contrary, very limited number of vaccine-specific T-cell clones was recruited from the naive pool. Furthermore, baseline quantity of vaccine-specific central memory helper T-cells and clonotype richness of this population directly correlated with the vaccination efficacy. Our findings suggest that the deliberate recruitment of pre-existing cross-reactive cellular memory might help to improve vaccination outcome.
Досліджено екзогенні та ендогенні регуляторні впливи на стан ліпідного метаболізму за допомогою вивчення жирнокислотного складу їжі та експресії регуляторного протеїну L-FABP у 43 осіб без діабету (23 із підвищенням вмісту глюкози та/або холестерину крові, 20-група контролю) та у 76 пацієнтів з ускладненим цукровим діабетом 2-го типу (ЦД2). Основною відмінністю ліпідного обміну пацієнтів з ЦД2 та осіб без діабету виявлено суттєву різницю перерозподілу вмісту жирних кислот (ЖК) у мембранах еритроцитів у вигляді підвищення в 1,5 раза вмісту насичених і відповідне зниження ненасичених ЖК за рахунок поліненасичених (ПНЖК), а також підвищення вмісту сироваткового протеїну L-FABP в 1,5 раза. Вживання в їжу продуктів-джерел указаних типів ЖК за показником «раціональності споживання продуктів», отриманим на основі аналізу анкет харчування,не відрізнялося в групах осіб без діабету та з ЦД2. У осіб без діабету, але з підвищеним вмістом глюкози крові та/або холестерину, виявили зменшений індекс маси тіла, незначне підвищення вмісту ПНЖК у мембранах еритроцитів, концентрацію L-FABP в 1,2 раза меншу, ніж у відносно здорових осіб і вдвічі меншу, ніж у пацієнтів з ЦД2. Можна припустити, що за певних умов, саме зменшення експресії L-FABP на тлі підвищення вмісту ПНЖК у клітинах, не погіршує стан метаболічних зсувів, а запобігає розвитку ожиріння і діабету. Відсутність прямої залежності між екзогенним впливом у вигляді вживання продуктів-джерел ЖК та перерозподілом вмісту цих кислот у мембранах еритроцитів, що є ознакою розвитку діабету, але наявністьзв'язку експресії внутрішньоклітинного регуляторного протеїну L-FABP із вмістом ЖК, дає підставу вважати ендогенні клітинні механізми основою глибокого порушення ліпідного гомеостазу.
While virus-specific antibodies are broadly recognized as correlates of protection, virus-specific T cells are important for direct clearance of infected cells. Failure to generate hepatitis B virus (HBV)-specific antibodies is well-known in patients with end-stage renal disease. However, whether and to what extent HBV-specific cellular immunity is altered in this population and how it influences humoral immunity is not clear. To address it, we analyzed HBV-reactive T cells and antibodies in hemodialysis patients post vaccination. 29 hemodialysis patients and 10 healthy controls were enrolled in a cross-sectional study. Using multiparameter flow cytometry, HBV-reactive T cells were analyzed and functionally dissected based on granzyme B, interferon-γ (IFN-γ), tumor necrosis factor alpha (TNF-α), interleukin-2 (IL-2), and IL-4 expression. Importantly, HBV-reactive CD4 + T cells were detected not only in all patients with sufficient titers but also in 70% of non-responders. Furthermore, a correlation between the magnitude of HBV-reactive CD4 + T cells and post-vaccination titers was observed. In summary, our data showed that HBV-reactive polyfunctional T cells were present in the majority of hemodialysis patients even if humoral immunity failed. Further studies are required to confirm their in vivo antiviral capacity. The ability to induce vaccine-reactive T cells paves new ways for improved vaccination and therapy protocols.
The aim: Is to determine the levels of markers of endothelial dysfunction in young men with myocardial infarction and their changes during the treatment with beta-blockers with different pharmacological properties. Materials and methods: 112 male patients of Caucasian race of the Ukrainian population under the age of 50 with MI. Group I received Nebivolol, group II – bisoprolol. Results: During the 6-month follow-up, positive dynamics of NOS-2 and ET-1 was observed. The level of NOS-2 in groups I – II was 4272.3±162.7, 4629.7±161.2 pg/mL, respectively (p<0.05). The dynamics of ET-1 showed significant decrease of its level in all groups Conclusions: Significant changes in markers of endothelial dysfunction, namely NOS3/eNOS, NOS2/iNOS and ET-1, are observed in young male patients of the Ukrainian population with MI. During 6 months of treatment, positive changes were observed in the form of an increase in NOS-3 levels and a significant decrease in ET-1 and NOS-2 levels. The inclusion of Nebivolol in the basic therapy for this group of patients is associated with an additional positive effect on the normalization of levels NO synthase and the reduction of ET-1.
Relevance. Investigation of polymorphism in a locus of CYP2E1 as the prognostic factor of drug-induced hepatotoxicity at anti-TB therapy is significant due to the influence of CYP2E1 on drug metabolism. The objective of the investigation is to analyze the association of rs2070676 СYP2E1 gene polymorphism with drug-induced hepatotoxicity by means of the clinical-laboratory values of serum transaminases at anti-TB treatment. Materials and methods. The study involved 47 patients with drug-susceptible tuberculosis first time discovered. 58 healthy volunteers comprised a control group. Laboratory indices were determined in venous blood three times: before the treatment as baseline; in 2 months of intensive therapy (isoniazid, rifampicin, ethambutol, pyrazinamide), then in 4 months of maintenance therapy (isoniazid, rifampicin). Serum activities of enzymes ALT, AST, and GGT were measured by standard algorithm on automatic analyzer BS-300. Analysis of rs2070676 polymorphism of CYP2E1 gene was performed by polymerase chain reaction using standard PureLink® Genomic DNA Kit for Purification of Genomic DNA; Manufacturer of INVITROGEN (USA). For statistical processing, IBM SPSS Statistics 23 was applied. Results. Investigation of serum ALT and AST in patients with major genotype CYP2E1 (C/C) showed the lower baseline ALT and AST levels comparing to the control group, which might be caused by suppression of hepatocytes functions at the development of the disease. Anti-TB treatment caused an increase in ALT and AST levels comparing to the baseline in patients with major CYP2E1 (C/C) genotype. In the group with C/G polymorphism, the baseline ALT level didn’t differ much from the baseline of the control group; it showed a decrease after intensive therapy and returned back to the initial level at maintenance therapy. This might be related to the certain protective property of СYP2E1 gene polymorphism. The AST level was increased after intensive therapy (to a smaller extent than for the patients with major C/C genotype) and remained on the same level at maintenance therapy. A study of GGT showed a gradual increase regardless of genotype. Conclusion. According to the data of the experiment, the status of hepatocytes in patients with tuberculosis at baseline and during treatment was different depending on the CYP2E1 genotype. The results of the experiment indicate that the CYP2E1 gene polymorphism has a certain protecting role. It reduces the level of drug metabolites and hepatotoxicity which causes mitochondrial dysfunction.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.