International Reviews of Immunology最新文献

SARS-CoV2 infection or COVID-19 has created panic around the world since its first origin in December 2019 in Wuhan city, China. The COVID-19 pandemic has infected more than 46.4 million people, with 1,199,727 deaths. The immune system plays a crucial role in the severity of COVID-19 and the development of pneumonia-induced acute lung injury (ALI) or acute respiratory distress syndrome (ARDS). Along with providing protection, both innate and T cell-based adaptive immune response dysregulate during severe SARS-CoV2 infection. This dysregulation is more pronounced in older population and patients with comorbidities (Diabetes, hypertension, obesity, other pulmonary and autoimmune diseases). However, COVID-19 patients develop protective antibodies (Abs) against SARS-CoV2, but they do not long for last. The induction of the immune response against the pathogen also requires metabolic energy that generates through the process of immunometabolism. The change in the metabolic stage of immune cells from homeostasis to an inflammatory or infectious environment is called immunometabolic reprogramming. The article describes the cellular immunology (macrophages, T cells, B cells, dendritic cells, NK cells and pulmonary epithelial cells (PEC) and vascular endothelial cells) and the associated immune response during COVID-19. Immunometabolism may serve as a cell-specific therapeutic approach to target COVID-19.

As the most important innate immune component cancers invader, natural killer (NK) cells have a magnificent role in antitumor immunity without any prior sensitization. Different subsets of NK cells have distinct responses during tumor cell exposure, according to their phenotypes and environments. Their function is induced mainly by the activity of both inhibitory and activating receptors against cancerous cells. Since the immunosuppression in the tumor microenvironment of breast cancer patients has directly deteriorated the phenotype and disturbed the function of NK cells, recruiting compensatory mechanisms indicate promising outcomes for immunotherapeutic approaches. These evidences accentuate the importance of NK cell distinct features in protection against breast tumors. In this review, we discuss the several mechanisms involved in NK cells suppression which consequently promote tumor progression and disease recurrence in patients with breast cancer.

Coronavirus disease (COVID-19) is an emerging and highly infectious disease making global public health concern and socio-economic burden. It is caused due to Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2). It has the tendency to spread rapidly through person-to-person. Currently, several molecular diagnostic platforms such as PCR, qRT-PCR, reverse transcription loop-mediated isothermal amplification (RT-LAMP), CRISPR are utilized for the diagnosis of SARS-CoV-2. These conventional techniques are costly, time consuming and require sophisticated instrumentation facility with well trained personnel for testing. Hence, it is tough to provide testing en-masse to the people in developing countries. On the other hand, several serological biosensors such as lateral flow immunosensor, optical, electrochemical, microfluidics integrated electrochemical/fluorescence is currently utilized for the diagnosis of SARS-CoV-2. In current pandemic situation, there is an urgent need of rapid and efficient diagnosis on mass scale of SARS-CoV-2 for early stage detection. Early monitoring of viral infections can help to control and prevent the spreading of infections in large chunk of population. In this review, the SARS-CoV-2 and their biomarkers in biological samples, collection of samples and recently reported potential electrochemical immunosensors for the rapid diagnosis of SARS-CoV-2 are discussed.

Gut barrier controls the food tolerance as well as host defense against potential hazards. The gut epithelium has been extensively studied for its importance in the structure and function of gut barrier. Recently, a new concept of barrier, named gut vascular barrier (GVB) has been discovered in both mice and human. Subsequent studies identified the morphological characteristics of GVB, the involved signaling events and its association with clinical diseases. In current study, we will summarize recent breakthroughs of GVB, with particular attentions to the molecular basis of GVB dysfunction. We will perform bioinformatics analysis to compare the transcriptional profiles of endothelium between blood and lymphatic vessels, healthy and inflammatory bowel diseases (IBD), healthy and colorectal cancer in the absence or presence of liver metastasis. We will further discuss the significance of impaired GVB in associated diseases, including vascular diseases, IBD and cancer metastasis. Our study will provide insights into the new concept of gut barrier, and promote the development of new strategies toward the vascular endothelium in the management of various diseases.

The immunological synapse promotes receptors and ligands interaction in the contact interface between the T lymphocyte and the antigen presenting cell; glycosylation of the proteins involved in this biological process favors regulation of molecular interactions and development of the T lymphocyte effector response. Glycans in the immunological synapse influence cellular and molecular processes such as folding, expression, and structural stability of proteins, they also mediate ligand-receptor interaction and propagation of the intracellular signaling or inhibition of uncontrolled cellular activation that could lead to the development of autoimmunity, among others. It has been suggested that altered glycosylation of proteins that participate in the immunological synapse affects the signaling processes and cell proliferation, as well as exacerbation of the effector mechanisms of T cells that trigger systemic damage and autoimmunity. Understanding the role of glycans in the immune response has allowed for advances in the development of immunotherapies in different fields through the controlled and specific activation of the immune response. This review describes the structural and biological aspects of glycans associated with some molecules present in the immunological synapse, providing information that allows understanding the function of glycosylation in the interaction between the T lymphocyte and the antigen-presenting cell, as well as its impact on signaling and development regulation of T lymphocytes effector response.

Mouth and associated structures were regarded as separate entities from the rest of the body. However, there is a paradigm shift in this conception and oral health is now considered as a fundamental part of overall well-being. In recent years, the subject of oral-foci of infection has attained a resurgence in terms of systemic morbidities while limited observations denote the implication of chronic oral inflammation in the pathogenesis of eye diseases. Hitherto, there is a paucity for mechanistic insights underlying the reported link between periodontal disease (PD) and ocular comorbidities. In light of prevailing scientific evidence, this review article will focus on the understudied theme, that is, the impact of oral dysbiosis in the induction and/or progression of inflammatory eye diseases like diabetic retinopathy, scleritis, uveitis, glaucoma, age-related macular degeneration (AMD). Furthermore, the plausible mechanisms by which periodontal microbiota may trigger immune dysfunction in the Oro-optic-network and promote the development of PD-associated AMD have been discussed.

Activated B-cells diversify their antibody repertoire via somatic hypermutation (SHM) and class switch recombination (CSR). SHM is restricted to the variable region, whereas, CSR is confined to the constant region of immunoglobulin (Ig) genes. Activation-induced cytidine deaminase (AID) is a crucial player in the diversification of antibodies in the activated B-cell. AID catalyzes the deamination of cytidine (C) into uracil (U) at Ig genes. Subsequently, low fidelity repair of U:G mismatches may lead to mutations. Transcription is essential for the AID action, as it provides a transient single-strand DNA substrate. Since splicing is a co-transcriptional event, various splicing factors or regulators influence the transcription. Numerous splicing factors are known to regulate the AID targeting, function, Ig transcription, and AID splicing, which eventually influence antibody diversification processes. Splicing regulator SRSF1-3, a splicing isoform of serine arginine-rich splicing factor (SRSF1), and CTNNBL1, a spliceosome interacting factor, interact with AID and play a critical role in SHM. Likewise, a splicing regulator polypyrimidine tract binding protein-2 (PTBP2) and the debranching enzyme (DBR1) debranches primary switch transcripts which later forms G-quadruplex structures, and the S region guide RNAs direct AID to S region DNA. Moreover, AID shows several alternate splicing isoforms, like AID devoid of exon-4 (AIDΔE4) that is expressed in various pathological conditions. Interestingly, RBM5, a splicing regulator, is responsible for the skipping of AID exon 4. In this review, we discuss the role and significance of splicing factors in the AID mediated antibody diversification.

Lack of standardized therapeutic approaches is arguably the significant contributor to the high burden of mortality observed in the ongoing pandemic of the Coronavirus disease, 2019 (COVID-19). Evidence is accumulating on SARS-CoV-2 specific immune cell dysregulation and consequent tissue injury in COVID-19. Currently, no definite drugs or vaccines are available against the disease; however initial results of the ongoing clinical trials have raised some hope. In this article, taking insights from the emerging empirical evidence about host-virus interactions, we deliberate upon plausible pathogenic mechanisms and suitable therapeutic approaches for COVID-19.