The COVID-19 pandemic is still raging across the world. Everyday thousands of infected people lost their lives. What is worse, there is no specific medicine and we do not know when the end of the pandemic will come. The nearest global pandemic is the 1918 influenza, which caused about 50 million deaths and partly terminate the World War Ⅰ. We believe that no matter the virus H1N1 for the 1918 influenza or 2019-nCoV for COVID-19, they are essentially the same and the final cause of death is sepsis. The definition and diagnostic/management criteria of sepsis have been modified several times but the mortality rate has not been improved until date. Over decades, researchers focus either on the immunosuppression or on the excessive inflammatory response following trauma or body exposure to harmful stimuli. But the immune response is very complex with various regulating factors involved in, such as neurotransmitter, endocrine hormone, etc. Sepsis is not a kind of disease, instead a misbalance of the body following infection, trauma or other harmful stimulation. Therefore we should re-think sepsis comprehensively with the concept of systemic biology, i.e. inflammationomics.
Betacoronavirus ; Coronavirus Infections ; complications ; epidemiology ; immunology ; Humans ; Immune Tolerance ; Inflammation ; complications ; Influenza A Virus, H1N1 Subtype ; Influenza, Human ; complications ; epidemiology ; immunology ; Pandemics ; Pneumonia, Viral ; complications ; epidemiology ; immunology ; Sepsis ; etiology

The natural history of chronic hepatitis B (CHB) is complex and may run through different immune phases that may overlap. In particulars, the immune-tolerant phase is the most interesting and not as well understood as we thought. The concept of true immune tolerance have been under challenged from immunology points of view. The major international guidelines have not yet reached a consensus on the definition of the immune-tolerant phase. While positive hepatitis B e antigen (HBeAg), high serum hepatitis B virus (HBV) DNA and normal serum alanine aminotransferase (ALT) levels are the three key features of this phase, some guidelines also put age into consideration. A new nomenclature, Phase 1 or HBeAg-positive chronic HBV infection, is given by the latest European Association for the Study of the Liver (EASL) published in April 2017. While current guidelines advise against starting antiviral treatment for immune-tolerant CHB patients, some new data suggest treating such patients may reduce the risk of liver fibrosis progression and hepatocellular carcinoma.
Alanine Transaminase ; Allergy and Immunology ; Carcinoma, Hepatocellular ; Consensus ; DNA ; Hepatitis B ; Hepatitis B virus ; Hepatitis B, Chronic* ; Hepatitis, Chronic* ; Humans ; Immune Tolerance ; Liver ; Liver Cirrhosis ; Natural History

The liver has been characterized as a frontline lymphoid organ with complex immunological features such as liver immunity and liver tolerance. Liver tolerance plays an important role in liver diseases including acute inflammation, chronic infection, autoimmune disease, and tumors. The liver contains a large proportion of natural killer (NK) cells, which exhibit heterogeneity in phenotypic and functional characteristics. NK cell activation, well known for its role in the immune surveillance against tumor and pathogen-infected cells, depends on the balance between numerous activating and inhibitory signals. In addition to the innate direct "killer" functions, NK cell activity contributes to regulate innate and adaptive immunity (helper or regulator). Under the setting of liver diseases, NK cells are of great importance for stimulating or inhibiting immune responses, leading to either immune activation or immune tolerance. Here, we focus on the relationship between NK cell biology, such as their phenotypic features and functional diversity, and liver diseases.
Adaptive Immunity ; Animals ; Autoimmune Diseases ; immunology ; Humans ; Immune Tolerance ; Immunity, Innate ; Killer Cells, Natural ; immunology ; Liver Diseases ; immunology ; Mice

Objective: Due to the special anatomical structure and pathophysiological mechanism of the central nervous system (CNS), there is a big difference between the repair of brain injury and other systems of the body. More and more evidence shows that targetedly reducing the autoimmune response of brain tissue without affecting the immune function in other parts of the body will be the best optimized treatment for brain injury. Data Sources: This review was based on data in articles published in PubMed up to June 5, 2017, with the following keywords: "immune tolerance", "traumatic brain injury", and "central nervous system". Study Selection: Original articles and critical reviews on immune tolerance and brain damage were selected for this review. References of the retrieved articles were also screened to search for potentially relevant papers. Results: The CNS is isolated from the immune system through the blood-brain barrier. After brain injury, brain antigens are released into the systemic circulation to induce damaging immune responses. Immune tolerance can effectively reduce the brain edema and neurological inflammatory response after brain injury, which is beneficial to the recovery of neurological function. The clinical application prospect and theoretical research value of the treatment of immune tolerance on traumatic brain injury (TBI) is worth attention. Conclusions The establishment of immune tolerance mechanism has a high clinical value in the treatment of TBI. It opens up new opportunities for the treatment of brain damage.
Brain ; immunology ; Brain Injuries, Traumatic ; immunology ; therapy ; Central Nervous System ; Humans ; Immune Tolerance ; Immunotherapy

Immunosuppressive regulatory T lymphocytes (Treg) expressing the transcription factor Foxp3 play a vital role in the maintenance of tolerance of the immune-system to self and innocuous non-self. Most Treg that are critical for the maintenance of tolerance to self, develop as an independent T-cell lineage from common T cell precursors in the thymus. In this organ, their differentiation requires signals from the T cell receptor for antigen, from co-stimulatory molecules, as well as from cytokine-receptors. Here we focus on the cytokines implicated in thymic development of Treg, with a particular emphasis on the roles of interleukin-2 (IL-2) and IL-15. The more recently appreciated involvement of TGF-β in thymic Treg development is also briefly discussed. Finally, we discuss how cytokine-dependence of Treg development allows for temporal, quantitative, and potentially qualitative modulation of this process.
Animals ; Cell Differentiation ; genetics ; Cytokines ; immunology ; Forkhead Transcription Factors ; genetics ; immunology ; Gene Expression Regulation ; Immune Tolerance ; genetics ; Interleukin-15 ; genetics ; immunology ; Interleukin-2 ; genetics ; immunology ; Mice ; Receptors, Antigen, T-Cell ; genetics ; immunology ; T-Lymphocytes, Regulatory ; immunology ; Transforming Growth Factor beta ; genetics ; immunology

Preterm infants are a special group, and related severe neurological, respiratory, and digestive disorders have high disability/fatality rates. Allogeneic cell transplantation may be an effective method for the prevention and treatment of these diseases. At present, animal studies have been conducted for allogeneic cell transplantation in the treatment of hypoxic-ischemic encephalopathy, bronchopulmonary dysplasia, and necrotizing enterocolitis. The main difficulty of this technique is graft-versus-host reaction (GVHR), and successful induction of immune tolerance needs to be achieved in order to solve this problem. This article reviews the research advances in immune tolerance of allogeneic cell transplantation in preterm infants.
Apoptosis ; Cell Transplantation ; adverse effects ; Cytokines ; physiology ; Graft vs Host Reaction ; Humans ; Immune Tolerance ; Infant, Newborn ; Infant, Premature ; immunology ; Transplantation, Homologous

No abstract available.
Adult ; Female ; Graft Rejection/immunology/*prevention & control ; Graft Survival ; *Hematopoietic Stem Cell Transplantation ; Humans ; *Immune Tolerance ; Immunosuppressive Agents/therapeutic use ; Kidney Failure, Chronic/diagnosis/*surgery ; *Kidney Transplantation ; Living Donors ; Siblings ; Time Factors ; *Transplantation Chimera ; Treatment Outcome

OBJECTIVETo explore progesterone-induced blocking factor (PIBF) expression in the placenta and blood of patients with severe preeclampsia and its relationship with immune tolerance imbalance.

METHODSForty-seven patients admitted between January and December, 2012 were enrolled in this study, including 25 patients with early-onset severe preeclampsia (EOPE) and 22 with late-onset severe preeclampsia (LOPE), with 25 women with normal pregnancy serving as control group. The antenatal blood and postpartum placenta were collected for immunohistochemical staining to detect PIBF expression in the placenta and for testing serum PIBF level using ELISA. Flow cytometry was used to detect the percentage of circulating Th1 and Th2 cells and the Th1/Th2 ratio was calculated.

RESULTSPIBF was expressed in decidual cells, syncytiotrophoblasts and partial cytotrophablasts. The serum PIBF levels were 213.58 ± 44.93 ng/ml in EOPE group, 243.00∓61.19 ng/ml in LOPE group and 273.91 ± 48.57 ng/ml in control group. There were significant differences in serum PIBF, blood Th1/Th2 and placenta PIBF-IOD among the 3 groups (P<0.05). EOPE group had significantly lower serum PIBF, lower llacental PIBF quantity (PIBF-IOD) and higher blood Th1/Th2 than the control group (P<0.05). Serum PIBF in women with severe preeclampsia was positively correlated with placenta PIBF-IOD and negatively with blood Th1/Th2 ratio (P<0.05), but a negative correlation between serum PIBF and 24-hour urinary protein was found only in EOPE group (P<0.05).

CONCLUSIONThe immune tolerance imbalance mediated by PIBF may participate in the pathogenesis of severe preeclampsia. PIBF, the immune suppressor secreted by lymphocytes of pregnancy women, is also a protective factor against severe preeclampsia, which is expected to be a new target in therapy.

Case-Control Studies ; Enzyme-Linked Immunosorbent Assay ; Female ; Humans ; Immune Tolerance ; Placenta ; metabolism ; Pre-Eclampsia ; immunology ; Pregnancy ; Pregnancy Proteins ; blood ; metabolism ; Suppressor Factors, Immunologic ; blood ; metabolism ; Th1-Th2 Balance

Animals ; Antibodies ; immunology ; therapeutic use ; Female ; Graves Disease ; immunology ; prevention & control ; Immune Tolerance ; immunology ; Mice ; Mice, Inbred BALB C ; Receptors, Thyrotropin ; immunology

This study was aimed to explore the effects of blocking B7/CD28 and CD40/CD154 co-stimulatory signals on immune function of sensitized mice', and provide the evidences of acquired immune tolerance for allogeneic bone marrow transplantation. The mice sensitized on 7 day before transplant were divided into 4 groups: (1)CTLA4Ig+ anti-CD154 isotype control IgG; (2)anti-CD154 +CTLA4Ig isotype control IgG; (3)CTLA4Ig and anti-CD154; (4)isotype control IgG of CTLA4Ig and anti-CD154. CTLA4Ig and anti-CD154 used in normal BALB/c mice as isotype control IgG. Each mouse in all groups received CTLA4Ig and anti-CD154 (or corresponding isotype control IgG) 500 µg respectively, and was injected via tail vein on 7 day before transplant. There were 5 mice in each group. The mice were sacrificed on day 0, then the number of CD19(+)CD69(+)B cells, CD44(high)/CD62L(high) and CD44(high)/CD62L(low)/- T cells were measured by flow cytometry. Changes of cytokines and sensitized antibody were tested by ELISA or flow cytometry. The results showed that the numbers of CD19(+)CD69(+)B cells were significantly increased in comparison with the normal group (P < 0.01) , whereas the numbers of cells were significantly decreased when blocking B7/CD28 or /and CD40/CD154 co-stimulatory signals (P < 0.01) . Blocking these 2 signals together displayed a synergistic effect (P < 0.01) . The central memory and effector T cells were defined as CD44(high)/CD62L(high) and CD44(high)/CD62L(low)/- respectively, those increased significantly after sensitized in comparison with those in normal group, whereas their numbers decreased when blocking B7/CD28 or/and CD40/CD154 co-stimulatory signals. Blocking these two signals together, displayed a synergistic effect (P < 0.01). Cytokines, IgG and IgM in all groups were not significantly different. Sensitizing antibody test showed that the fluorescence intensity of sensitized group significantly increased as compared with normal group, whereas fluorescence intensity of CTLA4Ig or/and anti-CD154 treated groups significantly decreased as compared with sensitized group (P < 0.01) . It is concluded that blocking the B7/CD28 or/and CD40/CD154 co-stimulatory signal can inhibit the cellular and humoral immune function, whereas blocking these two signals together displays a synergistic effect.
Animals ; B7-1 Antigen ; metabolism ; Bone Marrow Transplantation ; CD28 Antigens ; metabolism ; CD40 Antigens ; metabolism ; CD40 Ligand ; metabolism ; Immune Tolerance ; immunology ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Signal Transduction ; Transplantation, Homologous