Field Of Immunology Research Articles

Innovative PBMC-derived humanized mouse model reveals CD8+ T cell-intrinsic regulation during antitumor immunity.

The PBMC-derived humanized mouse model (PBMC model) may serve as an excellent tool in the field of immunology for both preclinical research and personalized therapeutic strategy development. However, single transplantation of complete PBMCs without modifications prevents the identification of cell type-specific factors that are potentially involved in modulating cell-intrinsic functions for the immune response. Here, we establish an innovative strategy for PBMC model generation, where two-step transplantations coupled with cell type-specific gene manipulation were conducted to evaluate the potential role of CD8+ T cell-intrinsic factors in regulating antitumor immunity toward PDX-based tumors. This method readily yields over 10% of human CD45+ cells within the PBMCs of humanized mice with high editing efficiency of gene expression in CD8+ T cells that can be subsequently detected in the tumor microenvironment (TME). Our work provides a new method to generate a PBMC-derived humanized mouse model for investigating regulators of interest during antitumor immunity in a cell type-specific manner.

Genomic profiling at a single center cracks the code in inborn errors of immunity.

Inborn errors of immunity (IEI) entail a diverse group of disorders resulting from hereditary or de novo mutations in single genes, leading to immune dysregulation. This study explores the clinical utility of next-generation sequencing (NGS) techniques in diagnosing monogenic immune defects. Eight patients attending the immunodeficiency clinic and with unclassified antibody deficiency were included in the analysis. Clinical records, immune characteristics, and family histories were reviewed, and a target gene panel (TGP) sequencing was performed to identify pathogenic variants. TGPs identified seven variants in TNFRSF13B (TACI), CARMIL2, STAT1, STAT3, and ORAI1 genes. These findings provided definitive diagnoses and proper prognostic assessment. Patients exhibited a wide range of clinical manifestations, including recurrent infections, autoimmune cytopenias, and organ-specific complications. The genetic diversity observed highlights the importance of genetic testing in diagnosing IEIs and tailoring treatments. This study underscores the role of TGPs in diagnosing IEIs, revealing significant genetic heterogeneity and phenotypic variability. They offer a precise tool for identifying underlying genetic defects, facilitating personalized medicine approaches, and eventually improving patient outcomes. The findings emphasize the need for comprehensive genetic testing to uncover novel pathogenic variants, enhancing our understanding of immune system dysfunction. NGS is a critical tool for the management of IEI, enabling precise diagnosis and personalized treatment strategies. Despite resource limitations, the progressive affordability is likely to expand its clinical utility, ultimately improving patient care and advancing the field of immunology. In the meantime, accurate phenotypic assessment is essential for resource optimization and case prioritization.

Predictive signatures of immune response to vaccination and implications of the immune setpoint remodeling.

In 2020, I featured two articles in the "mSphere of Influence" commentary series that had profound implications for the field of immunology and helped shape my research perspective. These articles were "Global Analyses of Human Immune Variation Reveal Baseline Predictors of Postvaccination Responses" by Tsang et al. (Cell 157:499-513, 2014, https://doi.org/10.1016/j.cell.2014.03.031) and "A crowdsourced analysis to identify ab initio molecular signatures predictive of susceptibility to viral infection" by Fourati et al. (Nat Commun 9:4418, 2018, https://doi.org/10.1038/s41467-018-06735-8). From these topics, the identification of signatures predictive of immune responses to vaccination has greatly advanced and pivoted our understanding of how the immune state at the time of vaccination predicts (and potentially determines) vaccination outcomes. While most of this work has been done using influenza vaccination as a model, pan-vaccine signatures have been also identified. The key implications are their potential use to predict who will respond to vaccinations and to inform strategies for fine-tuning the immune setpoint to enhance immune responses. In addition, investigations in this area led us to understand that immune perturbations, such as acute infections and vaccinations, can remodel the baseline immune state and alter immune responses to future exposures, expanding this exciting field of research. These processes are likely epigenetically encoded, and some examples have already been identified and are discussed in this minireview. Therefore, further research is essential to gain a deeper understanding of how immune exposures modify the epigenome and transcriptome, influence the immune setpoint in response to vaccination, and define its exposure-specific characteristics.

Complement regulators as novel targets for anti-cancer therapy: A comprehensive review.

Cancer remains a formidable global health challenge requiring the continued exploration of innovative therapeutic approaches. While traditional treatment strategies including surgery, chemotherapy, and radiation therapy have had some success, primarily in early-stage disease, the quest for more targeted, personalized, safer, and effective therapies remains an ongoing pursuit. Over the past decade, significant advances in the field of tumor immunology have dramatically shifted a focus towards immunotherapy, although the ability to harness and coopt the immune system to treat cancer is still just beginning to be realized. One important area that has yet to be fully explored is the complement system, an integral part of innate immunity that has gathered attention recently as a source of potential targets for anti-cancer therapy. The complement system has a complex and context dependent role in cancer biology in that it not only contributes to immune surveillance but also may promote tumor progression. Complement regulators, including CD46, CD55, CD59, and complement factor H, exercise defined control over complement activation, and have also been acknowledged for their role in the tumor microenvironment. This review explores the intricate role of complement regulators in cancer development and progression, examining their potential as therapeutic targets, current strategies, challenges, and the evolving landscape of clinical research.

A Current Perspective of Medical Informatics Developments for a Clinical Translation of (Non-coding)RNAs and Single-Cell Technologies.

The journey from laboratory research to clinical practice is marked by significant advancements in the fields of single-cell technologies and non-coding RNA (ncRNA) research. This convergence may reshape our approach to personalized medicine, offering groundbreaking insights and treatments in various clinical settings. This chapter discusses advancements in (nc)RNAs in the clinics, innovations in single-cell technologies and algorithms, and the impact on actual precision medicine, showing the integration of single-cell and ncRNA research can have a tangible impact on precision medicine. Case studies in Oncology, Immunology, and other fields demonstrate how these technologies can guide treatment decisions, tailor therapies to individual patients, and improve outcomes. This approach is particularly potent in addressing diseases with high inter- and intra-tumor heterogeneity. The final sections address standardization, data integration, and analysis challenges because the complexity and volume of data generated by single-cell and ncRNA research poses significant challenges. Medical Informatics is not just a support tool but could be seen as a pivotal component in advancing clinical applications of single-cell and ncRNA research by bridging the gap between bench and bedside. The future of personalized medicine depends on our ability to harness the power of these technologies, and Medical Informatics in combination with ncRNA and single-cell technologies may stand at the forefront of this endeavor.

Glial-immune interactions in barrier organs.

Neuro-immune interactions within barrier organs, such as lung, gut, and skin, are crucial in regulating tissue homeostasis, inflammatory responses, and host defence. Our rapidly advancing understanding of peripheral neuroimmunology is transforming the field of barrier tissue immunology, offering a fresh perspective for developing therapies for complex chronic inflammatory disorders affecting barrier organs. However, most studies have primarily examined interactions between the peripheral nervous system and the immune system from a neuron-focused perspective, while glial cells, the nonneuronal cells of the nervous system, have received less attention. Glial cells were long considered as mere bystanders, only supporting their neuronal neighbours, but recent discoveries mainly on enteric glial cells in the intestine have implicated these cells in immune-regulation and inflammatory disease pathogenesis. In this review, we will highlight the bi-directional interactions between peripheral glial cells and the immune system and discuss the emerging immune regulatory functions of glial cells in barrier organs.

Green synthesis of Pd nanoparticle embedded into chitosan-pectin polymeric composite as an efficient nanocatalyst in the Suzuki-Miyaura coupling reactions and accelerating the osteoarthritis articular cartilage repair

A new and efficient nanocatalyst, CS-Pec/Pd NPs, was developed using a simple and effective synthesis approach. This nanocatalyst exhibited outstanding performance and reusability in promoting Suzuki reactions involving variety of aryl halides with phenylboronic acid. The chitosan-pectin (CS-Pec) matrix acted as a reliable bio template, facilitating the in situ reduction and stabilization of Pd nanoparticles, all without the need for harmful chemicals. Pd(0) nanoparticles were evenly dispersed over the functionalized surface of CS-Pec. Detailed characterization of the nanocatalyst was carried out using advanced techniques, including FT-IR, FE-SEM, EDX, TEM, EDS-elemental mapping, and XRD. The CS-Pec/Pd NPs nanocatalyst was tested in Suzuki–Miyaura coupling, demonstrating excellent functional group compatibility and consistently achieving good to high yields of biphenyl products. Moreover, the nanocatalyst displayed superior catalytic activity and maintained high efficiency even after multiple reaction cycles, underscoring its potential as a sustainable and recyclable catalyst. CS-Pec/Pd NPs were successfully utilized to inhibit abnormal angiogenesis and fibrosis at the injury site. The histological test showed an increase in chondrocyte proliferation and cartilage matrix synthesis due to the presence of CS-Pec/Pd NPs, as well as a decrease in the formation of abnormal vasculature. The research revealed that the application of CS-Pec/Pd NPs expedited the recovery process post-injury within a span of three weeks. Additionally, we emphasized the advantageous impact of CS-Pec/Pd NPs on facilitating the development of cartilage in a controlled laboratory environment. Within the field of immunology, the CS-Pec/Pd NPs exhibited a reduction in the levels of TNF-α, IL-1β, MMPs, and p-p65 expression. The cellular redox homeostasis modulation linked to the Nrf2 pathway may be the cause of this phenomenon. The findings of this study ultimately validated the beneficial effects of CS-Pec/Pd NPs in enhancing the restoration of osteoarthritis articular cartilage

Valery Aleksandrovich Chereshnev – organizer of the immunological service in the Western Urals

The article is dedicated to the 80th anniversary of Valery Aleksandrovich Chereshnev, a Russian scientist, academician of the Russian Academy of Sciences, known for his works in the field of immunology and pathophysiology. V.A. Chereshnev began his career at Perm State Medical Institute, where he continued his postgraduate studies after graduating with honors. In 1970, he defended his PhD thesis on the topic “On the role of the properties of microbial cells and macroorganisms in the mechanism of development of an early phagocytic reaction to the introduction of typhoid vaccine”. In 1982, he defended his doctoral dissertation on the topic “Closed chest injury in combination with gamma irradiation (clinic, pathogenesis, treatment, medical protection).” He worked as a lecturer and professor in various educational institutions, and also headed scientific laboratories. In 1988, he became the director of the Institute of Ecology and Genetics of Microorganisms, Ural Branch of the Russian Academy of Sciences, and then organized a branch in Yekaterinburg, which was later transformed into the Institute of Immunology and Physiology, Ural Branch of the Russian Academy of Sciences, where he also became the director. Valery Aleksandrovich was elected a corresponding member of the Russian Academy of Sciences, academician of the Russian Academy of Sciences, Chairman of the Ural Branch of the Russian Academy of Sciences and Vice-President of the Russian Academy of Sciences, Chairman of the Committee on Science and High Technologies of the State Duma of the Federal Assembly of the Russian Federation. In addition, he was elected President of the Russian Scientific Society of Immunologists, organized the Society of Immunologists of the Urals. Currently he is actively developing immunological services in the Western Urals.

The Hunt Lab Guide to De Novo Peptide Sequence Analysis by Tandem Mass Spectrometry

Donald Hunt has made seminal contributions to the fields of proteomics, immunology, epigenetics, and glycobiology. The foundation of every important work to come out of the Hunt Laboratory is de novo peptide sequencing. For decades, he taught hundreds of students, postdocs, engineers, and scientists to directly interpret mass spectral data. To honor his legacy and ensure that the art of de novo sequencing is not lost, we have adapted his teaching materials into "The Hunt Lab Guide to De Novo Peptide Sequence Analysis by Tandem Mass Spectrometry". In addition to the de novo sequencing tutorials, we present two freely available software tools that facilitate manual interpretation of mass spectra and validation of search results. The first, "Hunt Lab Peptide Fragment Calculator", calculates precursor and fragment mass-to-charge ratios for any peptide. The second program, "Predator Protein Fragment Calculator", was inspired in part by the fragment calculator developed in the Hunt Lab. Its capabilities are enhanced to facilitate interpretation of mass spectral data derived from intact proteins. We hope that the combination of these educational tools will continue to benefit students and researchers by empowering them to interpret data on their own.

A proliferation-inducing ligand (APRIL) level among risk factors of ocular involvement in patients with Behçet's disease.

Ocular involvement is quite common in Behçet's disease (BD) and may cause crucial functional complications. Even though the mechanisms of BD remain unclear, advances in genetic and immunological fields have improved our understanding of the immunopathogenesis of BD ocular involvement. Little is known about the expression of a proliferation-inducing ligand (APRIL) in terms of ocular involvement in BD. The objective of this study was to determine whether serum APRIL concentrations are associated with ocular involvement in patients with BD. The study included 60 patients diagnosed with BD matched by age and sex to 30 healthy individuals. Every patient underwent a clinical evaluation, and the Behçet's Disease Current Activity Form (BDCAF) was utilized to quantify disease activity. All patients underwent a comprehensive ophthalmological assessment. Serum APRIL was assessed for patients as well as controls. One or more ocular manifestations were found in 42 BD patients (70%), while 18 patients (30%) had no ocular involvement. The mean level of serum APRIL levels was markedly elevated in BD patients, particularly those with ocular involvement, compared to both BD patients without ocular involvement and healthy individuals. A statistically significant association was determined between high APRIL concentration and development of uveitis, cataract, and hypopyon. Cutaneous lesions and arthritis were strong independent predictors for ocular involvement in BD patients. Overexpression of APRIL in patients with BD, particularly in terms of uveitis, cataract, and hypopyon, lends credence to the idea that B cell activating factors have an important function in BD. These findings may indicate that serum APRIL concentrations can differentiate a clinical subgroup of BD patients with ocular disease. As a result, finding a new therapeutic strategy targeting the APRIL pathway might be beneficial in BD patients suffering from ocular involvement.

Studying bats using a One Health lens: bridging the gap between bat virology and disease ecology.

Accumulating data suggest that some bat species host emerging viruses that are highly pathogenic in humans and agricultural animals. Laboratory-based studies have highlighted important adaptations in bat immune systems that allow them to better tolerate viral infections compared to humans. Simultaneously, ecological studies have discovered critical extrinsic factors, such as nutritional stress, that correlate with virus shedding in wild-caught bats. Despite some progress in independently understanding the role of bats as reservoirs of emerging viruses, there remains a significant gap in the molecular understanding of factors that drive virus spillover from bats. Driven by a collective goal of bridging the gap between the fields of bat virology, immunology, and disease ecology, we hosted a satellite symposium at the 2024 American Society for Virology meeting. Bringing together virologists, immunologists, and disease ecologists, we discussed the intrinsic and extrinsic factors such as virus receptor engagement, adaptive immunity, and virus ecology that influence spillover from bat hosts. This article summarizes the topics discussed during the symposium and emphasizes the need for interdisciplinary collaborations and resource sharing.

How Technical Advances Changed the Concept of Antibodies.

Shaped by advances in scientific instrumentation and experimental techniques, the concept of antibody has undergone profound transformations throughout the history of immunology. Serological assays, separation techniques, protein fragmentation techniques, molecular biology techniques, and other methodological innovations did not only serve to produce data on the structure and function of these molecules but, by framing antibodies into a unique facet of experimental investigation, were effectively redefining and reconceptualizing these molecules for the scientific community. The characteristics and properties of antibodies observed in experimental settings were often directly extrapolated to their presumed nature in living organisms, as exemplified by the literal identification of antibodies with a gamma electrophoretic fraction in the 1930s. Stemming from parallel advances in related fields such as molecular biology and biochemistry, the introduction of novel techniques was driving shifts in the field of immunology, establishing novel frameworks of theoretical conceptualization and understanding. Technological innovation in experimental techniques continues to shape our view of these molecules, driving progress in both basic immunology and therapeutic applications.

Neurophysiology and Molecular Basis of Cognitive Behavioral Therapy for Patients with Insomnia: Implications for Non-Pharmacological Approaches.

Cognitive behavioral therapy for insomnia (CBT-I) is a widely used psychological intervention known for its effectiveness in improving insomnia symptoms. However, the neurophysiological mechanisms underlying the cognitive-behavioral treatment of insomnia remain unclear. This narrative review aimed to elucidate the neurophysiological and molecular mechanisms of CBT-I, focusing on the fields of psychology, neurophysiology, neuroendocrinology, immunology, medical microbiology, epigenetics, neuroimaging and brain function. A comprehensive search was conducted using databases including: PubMed, Embase, PsycINFO and Web of Science, with customized search strategies tailored to each database that included controlled vocabulary and alternative synonyms. It revealed that CBT-I may have a beneficial effect on the central nervous system, boost the immune system, upregulate genes involved in interferon and antibody responses, enhance functional connectivity between the hippocampus and frontoparietal areas and increase cortical gray matter thickness. In conclusion, an integrated model is proposed that elucidates the mechanisms of CBT-I and offers a new direction for investigations into its neurophysiological mechanisms.

Tumor Immunology Unveiled: Advances, Challenges, and Future Prospects in Cancer Immunotherapy

Among the most important disciplines in the field of immunology, tumor immunology holds a significant place due to its focus on the interaction between tumors and the immune system. With the advancement of immunotherapy technologies in recent years, tumor immunology has emerged as one of the most exciting areas in cancer research. In this article, we will examine in detail the research progress in tumor immunology, including the mechanisms by which tumor cells evade the immune system, the application of immune checkpoint inhibitors, the development of tumor vaccines and their application in clinical practice, and how the tumor microenvironment impacts immunotherapy.

Mass Spectrometry–Based Proteomics for the Masses: Peptide and Protein Identification in the Hunt Laboratory During the 2000’s

There has been a rapid increase in the number of individuals utilizing mass spectrometry-based proteomics to study complex biological systems and questions since the start of the 2000's. Building off the advancements in ionization and liquid chromatography scientists continued to push towards technology that would enable in-depth analysis of biological specimen. Donald F Hunt and the Hunt laboratory were major contributors to this effort with their work on improving upon existing Fourier Transform MS, development of electron transfer dissociation, and continued work on ion-ion reactions to improve intact protein analysis. Collaboration with other instrumentation laboratories and instrument companies led to the sharing of technology and eventual commercialization providing greater access. Additionally, the Hunt laboratory spread the gospel of MS-based proteomics through collaborations that lasted decades with other scientists who were experts in immunology, cellular signaling, epigenetics, and other fascinating fields. This article attempts to highlight the many contributions of Don and the Hunt laboratory to peptide and protein identification since the year 2000.

Is modulation of immune checkpoints on glioblastoma-infiltrating myeloid cells a viable therapeutic strategy?

The field of immunology has traditionally focused on immune checkpoint modulation of adaptive immune cells. However, many malignancies such as glioblastoma are mostly devoid of T cells and rather are enriched with immunosuppressive myeloid cells of the innate immune system. While some immune checkpoint targets are shared between adaptive and innate immunity, myeloid-specific checkpoints could also serve as potential therapeutics. To better understand the impact of immune checkpoint blockade on myeloid cells, we systematically summarize the current literature focusing on the direct immunological effects of PD-L1/PD-1, CD24/Siglec-10, collagen/LAIR-1, CX3CL1/CX3CR1, and CXCL10/CXCR3. By synthesizing the molecular mechanisms and the translational implications, we aim to prioritize agents in this category of therapeutics for glioblastoma.

The mouse monoclonal antibody 4E3 is specific for the G1m17 allotype of human IgG1

Allotype is an amino acid variation within the immunoglobulin isotypes. Four allotypes have been described for human IgG1 and two of them (G1m3 and G1m17) are located at position 214 in the CH1 region of the gamma chain. Various diseases have been associated with allotype expression, making the allotype research an interesting field in immunology. However, allotype-specific reagents are rare. In the present study the specificity of a widely used and commercially available IgG1-specific monoclonal antibody named 4E3, described as binding to the hinge region of IgG1, was evaluated. Using the ImmunoCAP™ assay technology, surprisingly no IgG1 was measured in 13 of 23 human serum and plasma samples when 4E3 was used in an antibody-enzyme conjugate as detection reagent. Further evaluation of 4E3 using eight IgG1 myeloma paraproteins revealed that 4E3 did not bind to three of them. No association was seen between the binding pattern and myeloma light chain glycosylation or the kappa or light chain use. By comparing the myeloma paraprotein binding patterns of 4E3 and TM14 (a monoclonal antibody with known G1m3 specificity), it was indicated that 4E3 only bound to myeloma paraproteins expressing the G1m17 allotype. This was confirmed using recombinant human antibodies expressing either the G1m3 or G1m17 allotype. The G1m17 bias of 4E3 seen using ImmunoCAP was also observed in microtiter plate-based enzyme-linked immunosorbent assays. The antibody 4E3 has a G1m17 bias limiting its use in assays to measure IgG1 antibodies. However, it may be a valuable allotype-specific reagent.

Conserved allomorphs of MR1 drive the specificity of MR1-restricted TCRs.

Major histocompatibility complex class-1-related protein (MR1), unlike human leukocyte antigen (HLA) class-1, was until recently considered to be monomorphic. MR1 presents metabolites in the context of host responses to bacterial infection. MR1-restricted TCRs specific to tumor cells have been described, raising interest in their potential therapeutic application for cancer treatment. The diversity of MR1-ligand biology has broadened with the observation that single nucleotide variants (SNVs) exist within MR1 and that allelic variants can impact host immunity. The TCR from a MR1-restricted T-cell clone, MC.7.G5, with reported cancer specificity and pan-cancer activity, was cloned and expressed in Jurkat E6.1 TCRαβ- β2M- CD8+ NF-κB:CFP NFAT:eGFP AP-1:mCherry cells or in human donor T cells. Functional activity of 7G5.TCR-T was demonstrated using cytotoxicity assays and by measuring cytokine release after co-culture with cancer cell lines with or without loading of previously described MR1 ligands. MR1 allele sequencing was undertaken after the amplification of the MR1 gene region by PCR. In vivo studies were undertaken at Labcorp Drug Development (Ann Arbor, MI, USA) or Epistem Ltd (Manchester, UK). The TCR cloned from MC.7.G5 retained MR1-restricted functional cytotoxicity as 7G5.TCR-T. However, activity was not pan-cancer, as initially reported with the clone MC.7.G5. Recognition was restricted to cells expressing a SNV of MR1 (MR1*04) and was not cancer-specific. 7G5.TCR-T and 7G5-like TCR-T cells reacted to both cancer and healthy cells endogenously expressing MR1*04 SNVs, which encode R9H and H17R substitutions. This allelic specificity could be overcome by expressing supraphysiological levels of the wild-type MR1 (MR1*01) in cell lines. Healthy individuals harbor T cells reactive to MR1 variants displaying self-ligands expressed in cancer and benign tissues. Described "cancer-specific" MR1-restricted TCRs need further validation, covering conserved allomorphs of MR1. Ligands require identification to ensure targeting MR1 is restricted to those specific to cancer and not normal tissues. For the wider field of immunology and transplant biology, the observation that MR1*04 may behave as an alloantigen warrants further study. .

A study on loading multiple epitopes with a single peptide.

Epitopes, the basic functional units of antigens, hold great significance in the field of immunology. However, the structure and composition of epitopes and their interactions with antibodies remain unclear, which limits in-depth studies on epitopes and the development of subunit vaccines. In a previous study on the localization of anti-influenza HA monoclonal antibodies (mAbs), three strains with different characteristics reacted with the same peptide. In this study, by conventional immunological assays, computer homology modeling, and molecular docking simulations, we found that (1) the peptide could bind to three strains of mAbs with different reaction characteristics utilizing different combinations of immunodominant groups. (2) By computer molecular docking and simulation methods, the immunodominant groups on the two peptides could be combined into a multi-epitope peptide bound to six strains of mAbs. We established a method for multi-epitope peptide recombination from these immunodominant groups. (3) The immune effect of the recombinant multi-epitope peptide was better than that of a single peptide. Our findings facilitate the understanding of the composition of antigen epitopes and provide a theoretical and experimental basis for developing polyvalent vaccines and understanding immune responses at the molecular level.

Comparison of social network engagement performance between artificial intelligence‐generated content and human experts: A study in the field of immunology and allergology

Comparison of social network engagement performance between artificial intelligence‐generated content and human experts: A study in the field of immunology and allergology