Exploration of immunology最新文献

{"title":"Understanding sepsis-induced immunosuppression and organ dysfunctions: from immunosuppression to immunotherapy","authors":"D. Gupta, T. Sinha, Richa Pathak, S. Bhoi, D. Rao","doi":"10.37349/ei.2022.00070","DOIUrl":"https://doi.org/10.37349/ei.2022.00070","url":null,"abstract":"Sepsis is a life-threatening condition caused by dysregulated host immune response to infection, leading to persistent inflammation followed by immunosuppression. Sepsis represents a substantial global health problem owing to protracted inflammation, immune suppression, and susceptibility to nosocomial infections. Despite continuing progress in the development of antibiotics, fluid resuscitation, and other supportive care therapies, no specific immunomodulatory drugs or immunotherapeutic adjuncts for the treatment of sepsis are available to date. The advances in tertiary care facilities and patient care have improved the survival of sepsis patients in the initial hyper-inflammatory phase of sepsis. However, the majority of sepsis patients succumb later due to prolong immunosuppression. The sepsis-induced immune dysregulation and its long-term effects on mortality are under meticulous investigations that are still poorly defined. Sepsis leads to the impaired functions of the innate and adaptive immune systems. The exhaustion of T cells, reduced expression of human leukocytes antigen (HLA)-DR on monocytes, and induced uncontrolled apoptosis of immune cells have been reported as hallmark features of sepsis. Sepsis-induced immune cell apoptosis of immune cells is a primary contributing factor to the immunosuppression in sepsis. Preclinical studies have identified several new therapeutic targets for therapy in sepsis, including monoclonal antibodies (Abs) and anti-apoptotic agents to reduce T cells exhaustion, immune cells apoptosis, and restoring immune cells functions. Recent studies have centered on immune-modulatory therapy. The review article will focus solely on sepsis’ effects on innate and adaptive cells functions that contribute to immunosuppression. Finally, it is discussed how immune cells responsible for immunosuppression might be directly targeted to provide potential therapeutic benefits in treating sepsis and improving long-term survival.","PeriodicalId":93552,"journal":{"name":"Exploration of immunology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48081528","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The human microbiome and the tumor microenvironment","authors":"Joseph F. Murphy","doi":"10.37349/ei.2022.00069","DOIUrl":"https://doi.org/10.37349/ei.2022.00069","url":null,"abstract":"The human microbiome has emerged as an intriguing field of scientific research. Its role in human physiology impacts both health and disease, contributing to the enhancement or impairment of metabolic and immune functions. Sometimes referred to as our body’s “second genome”, the alteration of the microbiome’s bacterial ecology (dysbiosis), is linked to increasing numbers of illnesses, including cancer. The tumor microenvironment (TME) is the environment in which tumors grow and modulate the tumorigenic process depending on a myriad of distinct factors, including cell types, vascular system, and cytokines. Given the emerging relationship between the microbiome and the TME, this perspective aims to distill some of the key factors regulating the crosstalk between the microbiome and the TME. It also outlines why manipulating the microbiome may be a feasible strategy for anti-cancer therapy.","PeriodicalId":93552,"journal":{"name":"Exploration of immunology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43426256","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"γδ T cells: a sparkling star for clinical immunotherapy","authors":"Jiamian Zheng, Xuan Jiang, Haotian Zhao, Wandi Wang, Xiuli Wu, Zhenyi Jin","doi":"10.37349/ei.2022.00066","DOIUrl":"https://doi.org/10.37349/ei.2022.00066","url":null,"abstract":"Human γδ T cells are unconventional lymphocytes that function in innate and adaptive immune responses and immunosurveillance. These cells show potent cytotoxicity against tumor cells in a major histocompatibility complex unrestricted manner and have recently gained considerable attention as a sparkling star for clinical immunotherapy. Clinical immunotherapy trials with activated γδ T cells are tolerated well. However, clinical benefits are still unsatisfactory. Therefore, anti-tumor effects need to further increase the cytotoxicity of γδ T cells via several mechanisms, including the novel nitrogen-containing bisphosphonate products, adjuvant use with a bispecific antibody and chimeric antigen receptor, co-immunotherapy with γδ T cells plus immune checkpoint inhibitors, and adoptive immunotherapy with Vδ1 T cells and T cells engineered to express a defined γδ T cell receptor. Here, this article describes the crucial role of γδ T cells in anti-tumor immunity, concludes transduction strategies and summarizes the different development of novel approaches for clinical applications and cancer immunotherapy, which may be effective in overcoming current therapeutic limitations.","PeriodicalId":93552,"journal":{"name":"Exploration of immunology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48314731","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immune network operations in COVID-19","authors":"J. Burgos-Salcedo","doi":"10.37349/ei.2022.00068","DOIUrl":"https://doi.org/10.37349/ei.2022.00068","url":null,"abstract":"The immune system, whose nature lies in being a complex network of interactions, lends itself well to being represented and studied using graph theory. However, it should be noted that although the formalization of models of the immune system is relatively recent, the medical use of its signaling network structure has been carried out empirically for centuries in vaccinology, immunopathology, and clinical immunology, as evidenced by the development of effective vaccines, the management of transplant rejection, the management of allergies, and the treatment of certain types of cancer and autoimmune diseases. A network optimization analogy is proposed through the employment of the system dynamic formalism of causal loop diagrams (CLDs), where current network operations (also known as NetOps) in information technology (IT), are interpreted as immune NetOps in coronavirus disease 2019 (COVID-19) treatment. Traffic shaping corresponds to signaling pathway modulation by immunosuppressors. Data caching corresponds to the activation of innate immunity by application of Bacillus Calmette-Guerin (BCG) and other vaccines. Data compression corresponds with the activation of adaptative immune response by vaccination with the actual approved COVID-19 vaccines. Buffer tuning corresponds with concurrent activation of innate and adaptative or specialized immune cells and antibodies that attack and destroy foreign invaders by trained immunity-based vaccines to develop. The present study delineates some experimental extensions and future developments. Given the complex communication architecture of signal transduction in the immune system, it is apparent that multiple parallel pathways influencing and regulating each other are not the exception but the norm. Thus, the transition from empirical immune NetOps to analytical immune NetOps is a goal for the near future in biomedicine.","PeriodicalId":93552,"journal":{"name":"Exploration of immunology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44616485","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Contribution of immunology to build precision medicine in reproduction: present and future","authors":"A. Kazhalawi, M. Petitbarat, M. Rahmati, N. Lédée","doi":"10.37349/ei.2022.00067","DOIUrl":"https://doi.org/10.37349/ei.2022.00067","url":null,"abstract":"Infertility affects millions of people of reproductive age. The failure of a blastocyst to implant is a leading cause of psychological distress. It became increasingly evident that an effective immune dialogue occurs at each step in the fluids surrounding the oocyte, the spermatozoa, the embryo, or the endometrium. Exploring and deciphering this dialogue could potentially help understand why 50% of healthy euploid blastocysts fail to implant. Introducing immunology into reproductive medicine requires a change of mindset to bring immune hypothesis to clinical applications. Implantation of an embryo requires a prepared uterus in order to dialogue with the embryo, which is able to express and repair itself. Exploring the uterine immune profile of patients with previous implantation failures (IF) or recurrent miscarriages (RM) has already been developed and is under evaluation as a precision tool to equilibrate the uterine environment before implantation to increase the subsequent live birth rate after the embryo transfer. Immunology may also be fundamental in the future to identify through non-invasive procedure the competence of oocytes or embryos through reliable immune biomarkers quantified in follicular fluids or embryo supernatants during the in vitro fertilization (IVF) process. Non-invasive biomarkers would allow physicians to identify competent oocytes or embryos based on their ability to communicate with the mother and their energetic potential for all the self-repair processes that should occur during the preimplantation and the implantation period. This area of research is only beginning.","PeriodicalId":93552,"journal":{"name":"Exploration of immunology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45209514","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Uterine natural killer cells and successful pregnancy: from mouse experiments to human physiology","authors":"M. Faas","doi":"10.37349/ei.2022.00065","DOIUrl":"https://doi.org/10.37349/ei.2022.00065","url":null,"abstract":"Uterine natural killer (uNK) cells, a specific type of natural killer (NK) cells, are important cells at the foeto-maternal interface in humans as well as in mice. uNK cells are part of the innate lymphoid cells group 1. Especially in the mouse, but also in the rat, many in vivo studies have been performed to evaluate the role of uNK cells in placental development. These studies have shown that uNK cells are not indispensable to pregnancy, but that they play an important role in optimal decidual angiogenesis in early pregnancy, trophoblast invasion and spiral artery remodelling in the mouse placenta. Based on the mouse studies, various in vitro studies, as well as immunohistological studies of the human placenta from elective abortions, have shown that uNK cells have similar functions in the human placenta. In the present narrative review, the role of the uNK cells in the development of the mouse and rat placenta will be discussed first. Thereafter, studies on the role of human uNK cells in the human placenta will be reviewed and these studies will be discussed in the light of the knowledge on mouse uNK cells.","PeriodicalId":93552,"journal":{"name":"Exploration of immunology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43973027","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pathogenesis of the obstetric antiphospholipid syndrome: the key role of beta 2 glycoprotein I","authors":"P. Meroni, C. Grossi, F. Tedesco","doi":"10.37349/ei.2022.00064","DOIUrl":"https://doi.org/10.37349/ei.2022.00064","url":null,"abstract":"Antiphospholipid syndrome (APS) is defined by recurrent pregnancy morbidity and/or vascular thrombosis associated with the persistent presence of antibodies against anionic phospholipid-binding proteins. Beta 2 glycoprotein I (β2GPI) and prothrombin (PT) are the major antigens for antiphospholipid antibodies (aPL) detectable by functional coagulation [lupus anticoagulant (LA)] or solid-phase assays [anti-β2GPI-dependent cardiolipin (aCL) and anti-β2GPI]. β2GPI-dependent aPL are responsible for the positivity of the three classification laboratory criteria. While medium/high titers of antibodies against β2GPI are risk factors for both the vascular and the obstetric manifestations of APS, persistent low titers are also associated with pregnancy complications. There is evidence from animal models of aPL-dependent fetal loss and from in vitro systems that β2GPI-dependent aPL can be pathogenic. β2GPI is physiologically found in large quantities at the placental level being available for the specific antibodies circulating in the maternal blood. Once bound to the protein, the antibodies trigger a local inflammation via the activation of the complement cascade and affect trophoblast and decidual function. The final result is represented by defective placentation, while thrombotic events are apparently less important. β2GPI is a pleiotropic molecule with scavenging properties towards several molecules including apoptotic material and displays anti-oxidant activity. These functions may explain the β2GPI placental localization in an area of intensive tissue remodeling and low oxygen tension. Since β2GPI interacts also with the complement and the coagulation cascade, its binding with specific antibodies may affect the physiology of placentation in several ways.","PeriodicalId":93552,"journal":{"name":"Exploration of immunology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48839997","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Small molecules targeting endolysosomal acidification and signaling in sepsis and severe SARS-CoV-2 infection/COVID-19","authors":"M. Blaess, O. Sommerfeld, R. Csuk, H. Deigner","doi":"10.37349/ei.2022.00063","DOIUrl":"https://doi.org/10.37349/ei.2022.00063","url":null,"abstract":"Sepsis and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, and its severe form coronavirus disease 2019 (COVID-19), represent the major medical challenges of the modern era. Therapeutic options are limited, mostly symptomatic, partially relying on antibodies and corticosteroids and, in the case of SARS-CoV-2 infection, supplemented by the antiviral drug remdesivir, and more recently by molnupiravir, nirmatrelvir/ritonavir, and the Janus kinase (JAK) inhibitors tofacitinib and baricitinib. Sepsis and severe SARS-CoV-2 infection/COVID-19 share many features at the level of pathophysiology and pro-inflammatory mediators, thus enabling a common disease management strategy. New ideas in successfully targeting the prognostic severity and mortality marker pentraxin 3 (PTX3) in sepsis and severe SARS-CoV-2 infection/COVID-19; the complement (C3/C3a/C3aR and C5/C5a/C5aR axis); tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 expression; IL-6-triggered expression of C5aR receptor in vascular endothelial cells; and release of anti-inflammatory IL-10 are still missing. Small molecules with lysosomotropic characteristics such as the approved drugs amitriptyline, desloratadine, fluvoxamine, azelastine, and ambroxol have demonstrated their clinical benefits in rodent models of sepsis or clinical trials in COVID-19; however, their exact mode of action remains to be fully elucidated. Addressing disease-relevant targets such as viral infection of host cells, shedding of toll-like receptors (TLRs), expression of pro-inflammatory mediators such as TNF-α, IL-1β, IL-6, PTX3, and the complement receptor C5aR, highlight the advantages of this multi-target approach in comparison to current standards. Rational drug repurposing of approved drugs or screening for active compounds with virtually exclusively lysosomotropic pharmacologic effects is a major opportunity to improve prophylaxis and treatment of sepsis and/or SARS-CoV-2 infection, and its severe form COVID-19.","PeriodicalId":93552,"journal":{"name":"Exploration of immunology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47595014","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Endometriosis through an immunological lens: a pathophysiology based in immune dysregulation","authors":"Alison McCallion, Danielle J. Sisnett, Katherine B. Zutautas, Donya Hayati, Katherine G. Spiess, Stanimira Aleksieva, Harshavardhan Lingegowda, M. Koti, C. Tayade","doi":"10.37349/ei.2022.00062","DOIUrl":"https://doi.org/10.37349/ei.2022.00062","url":null,"abstract":"Endometriosis (EMS) is an inflammatory, gynaecologic disease characterized by the growth of endometrial tissues outside the uterus. With no satisfactory therapies or non-invasive diagnostics available, a shift in perspectives on EMS pathophysiology is overdue. The implication of immune dysregulation in EMS pathogenesis and disease progression has been an evolving area of research, with numerous immune and inflammatory pathways identified. Traditional theories regarding the establishment of endometriotic lesions have lacked mechanistic explanations for their proliferation and survival until recent research unearthed the involvement of mesenchymal stem cell (MSC) and myeloid-derived suppressor cells (MDSCs) in a complex network of immune-endocrine signaling. The unique immunology of EMS is likely owing to estrogen dominance, as endocrine imbalance reliably cultivates immune dysregulation. Many of the phenomena observed in EMS parallel immune biology seen in various cancers, including accelerated somatic mutations in endometrial epithelial cells. Here, the high mutational load leads to EMS neoantigen development which potentially contributes to the lesion immune microenvironment. As well, EMS manifests comorbidity with several chronic inflammatory diseases that share common dysregulation of the interleukin-23 (IL-23)/IL-17 pathway (as seen in inflammatory bowel disease, psoriasis, and rheumatoid arthritis). EMS is especially relevant to the study of chronic pelvic pain (CPP) as 60% of EMS patients experience this symptom and chronic inflammation is believed to be central to the process of pain sensitization. Since the onset of the disease usually occurs in adolescence, and diagnosis only occurs years later once moderate to severe symptoms have developed, it is vital to innovate non-invasive diagnostic tools for earlier detection. Several potential biomarkers are being studied, including some cytokines, gene signatures, and extracellular vesicle (EV) signatures. By incorporating the immune perspectives of EMS into our research, approaches to diagnosis, and treatment solutions, the field has more promising avenues to clearly define EMS and offer patients relief.","PeriodicalId":93552,"journal":{"name":"Exploration of immunology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43444151","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In COVID-19, antigen size lower or larger than 70 kDa modulates the sepsis and memory B cells","authors":"Francisco Javier Martín Oncina","doi":"10.37349/ei.2022.00061","DOIUrl":"https://doi.org/10.37349/ei.2022.00061","url":null,"abstract":"This review pretends to shed light on the immune processes occurring in the coronavirus disease 2019 (COVID-19) from a perspective based on the antigens size, lower or larger than 70 kDa. This cutoff size point explains the host type of immune response against the antigenic proteins of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which may lead to the development of the memory B cells or, conversely, the immune suppression, apoptosis, viral escape, and sepsis. Here, based on previous experimental work and the review of related literature, the following is proposed: antigens < 70 kDa can access the germinal center through the follicular conduits, where the activated B cells can present the processed antigen to specific naive CD4+ T cells that, in interaction with the major histocompatibility complex class II (MHC-II), trigger the immune response T helper type 2 (Th2). Conversely, antigens > 70 kDa cannot circulate through the narrow follicular conduits network and might be captured within the subcapsular sinus by the macrophages and dendritic follicular cells. Then, these cognate antigens are presented, via complement receptors, to the B cells that acquire and present them through the MHC-II to the specific naive CD4+ T cells, triggering the immune response Th1. The sustained infected cells lysis can overfeed high levels of unassembled viral proteins < 70 kDa, which can lead to a strong and persistent B cell receptor (BCR) activation, enhancing the Th2 immune response, releasing interleukin-10 (IL-10) and transforming growth factor-beta (TGF-β) that may lead to the immune paralysis, apoptosis, sepsis, and death. Finally, it is suggested that the polymerization of the viral antigens < 70 kDa into an antigenic polymer > 70 kDa could shift the immune response type from Th2 to Th1, developing the memory B cells and immunoglobulin G2 (IgG2) production, and avoiding the sepsis.","PeriodicalId":93552,"journal":{"name":"Exploration of immunology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41877584","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}