Natural killer (NK) cells directly lysis the virus-infected cells through rapidly releasing cytotoxic mediators and cytokines. The balance between inhibitory and activated receptors on the surface of NK cells, as well as the corresponding ligands expressed on target cells are involved in the regulation of the cytotoxic function of NK cells. NKG2A is one of the highly anticipated inhibitory receptors expressed on NK cells, which can inhibit the cytotoxicity of NK cells to autologous normal tissue cells through interacting with the ligand HLA-E. The studies have shown that HLA-E is overexpressed on virus-infected cells and forms a complex with peptides derived from viral proteins. The interaction of HLA-E and NKG2A can regulate the functions of NK cells, participateing the pathogenesis process of virus infectious diseases. This review outlines the characteristics of the molecular interaction between NKG2A and HLA-E, as well as the mechanisms of NKG2A-HLA-E axis in regulating NK cell responses.
BackgroundHemorrhagic fever with renal syndrome (HFRS) induced by Hantaan virus infection and heparin‐induced thrombocytopenia (HIT) are associated with symptoms such as thrombocytopenia and thrombosis. However, related molecules, such as anti–platelet factor 4 (PF4)/heparin antibodies, in patients with HFRS have not been evaluated.ObjectivesTo test plasma levels of anti‐PF4/heparin antibodies and study the possible role of these antibodies in HFRS pathogenesis.MethodsIndirect ELISA was used to determine plasma levels of anti‐PF4/heparin antibodies in 75 patients with HFRS and 20 normal controls. The 4Ts (thrombocytopenia, timing of platelet count fall, thrombosis or other sequelae, and other causes of thrombocytopenia) scoring system was used to determine the probability of HIT occurrence. A PF4‐enhanced platelet activation assay was used to detect the pathological effects of anti‐PF4/heparin antibodies. The laboratory/clinical features and viral load of all the patients were also assessed.ResultsOf the 75 patients with HFRS enrolled instudy, 69 had thrombocytopenia. Platelet count was negatively correlated with Hantaan viral load. Moreover, the optical density (OD) values of plasma antibodies against PF4/heparin in normal controls were less than 0.65, 4 patients tested strongly positive for anti‐PF4/heparin antibodies (OD values, 1.51–3.87), 21 patients were weakly positive (OD values, 0.66–0.74), and 50 patients were negative (OD values, 0.16–0.65). Moreover, all 4 patients who tested strongly positive for anti‐PF4/heparin antibodies showed a low probability of HIT (4Ts score of 3 or less) and had negative results in the PF4‐enhanced platelet activation assay.ConclusionsHantaan virus infection produces nonpathogenic antibodies against PF4/heparin; however, the generation mechanism of these antibodies requires further study.
The concept of "ntigen"is a relative one. The narrow concept of it condenses the process of activation of adaptive immune response and re-recognition of the same antigen, revealing the protective mechanism of vaccines with great significance for research and development of vaccines. However, the narrow concept involves adaptive immune system members: B cells, T cells and their effector products, which is difficult for beginners to understand the inherent meaning. Meanwhile, antigen classification fully summarizes the immune response process, so a variety of classification approach increases the difficulty in learning. Our teaching team analyzes the difficulties of this chapter in depth, and we implements the strategy that takes antibody structure and function as the breakthrough point and simplified adaptive immune response process as the core in teaching. A mind map that includes the main contents of this chapter is made during the process, which promotes the effectiveness of classroom teaching greatly.
Abstract Aggressive cancers are less sensitive to standard cancer treatments available, reducing overall survival rates and increasing relapse percentage in cancer patients. As a result, there is an increasing need for alternative therapeutics that will prolong the survival of patients. Within the last decade, methods to attenuate tumor immune evasion have become a centerpiece of tumor therapies. However, a major hurdle in tumor immunotherapy is the immunosuppression mediated by Regulatory T (Treg) cells, which can promote tumor progression through the suppression of tumor immune evasion. Therefore, the ability to modulate Treg function in the context of cancer could lead to more effective therapies. Here, we identify the ubiquitin-specific peptidase 22 (USP22), a member of the deubiquitination module of the SAGA chromatin modifying complex, as a specific regulator of Foxp3, the lineage-specifying transcription factor of Tregs. Treg-specific ablation of Usp22 in mice reduced Foxp3 at both the transcriptional and post-translational level, creating defects in their suppressive function and leading to spontaneous autoimmunity. Importantly, USP22 ablation protected against tumor growth in multiple cancer models. Collectively, our findings reveal a previously underappreciated physiological function of USP22 in maintaining Treg stability and identify USP22 as a potential target for cancer immunotherapy.
Hantaan orthohantavirus (HTNV) can cause hemorrhagic fever with renal syndrome (HFRS) characterized by acute kidney injury and hemorrhage. Neutrophils are the most abundant innate immune cell and the body's first line of defense against pathogens. Currently, an increasing number of studies have shown that neutrophils may be a mixed blessing in terms of viral infections. However, the role of neutrophils in HFRS patients with HTNV infection has not been fully declared. In this study, we analyzed plasma levels of both myeloperoxidase (MPO) and MPO-DNA in HFRS patients, together with the clinical parameters. Neutrophil-platelet aggregates (NPAs) during the acute and convalescent phases of HFRS were also assessed. The results showed that plasma MPO-DNA levels had no change in different disease phases or severities of HFRS patients. Whereas plasma MPO significantly increased in the acute phase and critical/severe groups of HFRS patients. Furthermore, plasma MPO was positively correlated with inflammatory clinical parameters, such as white blood cell counts, neutrophil counts, and renal injury-related parameters, such as blood urea nitrogen, blood uric acid, and serum creatinine, as well as negatively correlated with and platelet counts. In addition, NPAs increased both in acute and convalescent phase in HFRS patients compared with normal controls. These results suggested that elevated plasma MPO in HFRS patients correlated with disease severity, together with the increases of NPAs in HFRS patients, which may provide new insights into potential role of neutrophils in the pathogenesis of HFRS.
CD163, a hemoglobin scavenger receptor for haptoglobin-hemoglobin complexes, is expressed by monocytes/macrophages and is often shed as soluble CD163 (sCD163) in response to inflammatory stimuli. This scavenger receptor is reported to dampen the inflammatory response, and high plasma levels of sCD163, which are thought to reflect the total level of CD163 expression, may predict the severity of disease. To understand the role of sCD163 in the pathogenesis of hemorrhagic fever with renal syndrome (HFRS) better, the concentrations of sCD163 in plasma from 66 patients were quantified, and the relationships between sCD163 level and disease course, severity, and clinical parameters were analyzed. The level of plasma sCD163 in HFRS patients was elevated from fever onset and during the course of the disease, and it peaked in the oliguria stage at 874.5 (549.9–1138.0) ng/mL compared with controls at 192.8 (54.9–282.1) ng/mL. The correlations between plasma sCD163 and renal dysfunction suggest that sCD163 may play an important role in the development of acute renal failure in patients infected with Hantaan virus.
Hantaan viruses (HTNVs) are zoonotic pathogens transmitted mainly by rodents and capable of infecting humans. Increasing knowledge of the human response to HTNV infection can guide the development of new preventative vaccines and therapeutic strategies. Here, we show that HTNV can infect CD8+ T cells in vivo in patients diagnosed with hemorrhagic fever with renal syndrome (HFRS). Electron microscopy-mediated tracking of the life cycle and ultrastructure of HTNV-infected CD8+ T cells in vitro showed an association between notable increases in cytoplasmic multivesicular bodies and virus production. Notably, based on a clinical cohort of 280 patients, we found that circulating HTNV-infected CD8+ T cell numbers in blood were proportional to disease severity. These results demonstrate that viral infected CD8+ T cells may be used as an adjunct marker for monitoring HFRS disease progression and that modulating T cell functions may be explored for new treatment strategies.
In mild cognitive impairment (MCI), cognitive decline is associated with abnormal changes of cerebral blood flow (CBF). Arterial spin labeling magnetic resonance imaging (ASL-MRI) is an effective method for assessing regional cerebral blood flow (rCBF). However, the CBF estimated via ASL-MRI in MCI often differs between studies, and the consistency of CBF changes in MCI is unclear. In this study, 13 ASL-MRI studies with 495 MCI patients and 441 health controls were screened out from PubMed, Embase, Cochrane, Web of Science, Wanfang, and CNKI. An activation likelihood estimation (ALE) meta-analysis was performed to explore the brain regions with abnormal CBF in MCI. It showed that the decreased CBF in MCI was identified in the precuneus, inferior parietal lobule (IPL), superior occipital gyrus (SOG), middle temporal gyrus (MTG), and middle occipital gyrus (MOG), while the increased CBF in MCI was identified in the lentiform nucleus (LN) compared with healthy controls. The study characterized the abnormal pattern of regional CBF in MCI, which would promote our knowledge of MCI and might be used as a biomarker in clinic.https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=259633.
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