T cell immunopathogenesis and immunotherapeutic strategies for chronic hepatitis B virus infection

Hepatitis B is caused by the host immune response and T cells play a major role in the immunopathogenesis. More importantly,T cells not only destroy hepatocytes infected by hepatitis B virus(HBV),but also control HBV replication or eradicate HBV in a noncytolytic manner.Therefore,analysis of T cell immune response during acute and chronic HBV infection is important to develop a strategy for successful viral control,which could lead to immunotherapy for terminating persistent HBV infection.There have been many attempts at immunotherapy for chronic HBV infection,and some have shown promising results.High viral load has been shown to suppress antiviral immune responses and immunoinhibitory signals have been recently elucidated, therefore,viral suppression by nucleos(t)ide analogs, stimulation of antiviral immune response,and suppression of the immunoinhibitory signals must be combined to achieve desirable antiviral effects.

Immunopathogenesis of chronic hepatitis B

Chronic hepatitis B (CHB) is a widespread infectious disease with unfavorable outcomes and life-threatening consequences for patients, in spite of modern vaccination and antiviral treatment modalities. Cutting-edge experimental approaches have demonstrated key pathways that involve cross-talk between viral particles and host immune cells. All events, including penetration of hepatitis B virus (HBV) particles into host cells, establishing persistence, and chronization of CHB infection, and possibility of complete elimination of HBV particles are controlled by the immune system. Researchers have paid special attention to the replication capacity of HBV in host cells, which is associated with cellular changes that reflect presentation of viral antigens and variability of HBV antigen features. In addition, specific HBV proteins have an immune-modulating ability to initiate molecular mechanisms that “avoid” control by the immune system. The relationship between immunological shifts and chronic infection stages has been intensively studied since it was recognized that the immune system is a direct participant in the recurrent (cyclic) nature of CHB. Understanding the wide diversity of molecular pathways and the crosstalk between innate and adaptive immune system components will provide fresh insight into CHB immune pathogenesis and the possibilities of developing new treatment strategies for this disease.

The role of cell mediated immunopathogenesis in thyroid-associated ophthalmopathy

Currently, thyroid-associated ophthalmopathy (TAO) lacks effective treatment due to our lack of clarity in its immunopathogenesis. Orbital fibroblasts play a key role in altering inflammation and immune response in TAO, and are considered as the key target and effector cells in its pathogenesis. The orbit infiltrating CD34+ fibrocytes add on to the process by expressing high levels of autoantigens and inflammatory cytokines, while also differentiating into myofibroblasts or adipocytes. This review focuses on the role of orbital fibroblasts and CD34+ fibrocytes in the pathogenesis of TAO, highlighting the basis of emerging treatments.

Roles of microRNAs in immunopathogenesis of non-alcoholic fatty liver disease revealed by integrated analysis of microRNA and mRNA expression profiles

BACKGROUND： The integrative analysis of microRNA and mRNA expression profiles can elucidate microRNA-targeted gene function. We used this technique to elucidate insights into the immunological pathology of non-alcoholic fatty liver disease （NAFLD）. METHODS： We analyzed differentially expressed microRNA and mRNA expression profiles of CD4＋ T lymphocytes from the liver and mesenteric lymph nodes （MLNs） of mice with NAFLD using microarrays and RNA sequencing. Normal mice were used as controls. The target genes of microRNAs were predicted by TargetScan. Integrative analysis showed that the mRNAs were overlapped with microRNAs. Furthermore, the Gene Ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） analyses were performed to predict the key genes and pathways. Then, 16 microRNAs and 10 mRNAs were validated by qRT-PCR. RESULTS： Microarray analysis suggested that 170 microRNAs were significantly de-regulated in CD4＋ T lymphocytes from the liver between the two groups. Eighty mRNAs corresponded with microRNA targeted genes. KEGG analysis indicated that the MAPK pathway was consistently augmented in the liver of NAFLD mice. miR-23b, let-7e, miR-128 and miR-130b possibly played significant parts in the MAPK pathways. Furthermore, between the two groups, 237 microRNAs were significantly deregulated in CD4＋ T lymphocytes from MLNs. 38 mRNAs coincided with microRNA target genes. The metabolic pathway was consistently enriched in the MLNs of NAFLD mice. miR- 206-3p, miR-181a-Sp, miR-29c-3p and miR-30d-5p likely play important roles in the regulation of metabolic pathways. CONCLUSION： The results of this study presented a new perspective on the application of integrative analysis to identify complex regulation means involved in the immunological pathogenesis of NAFLD.

Crimean-Congo hemorrhagic fever from the immunopathogenesis, clinical, diagnostic, and therapeutic perspective: A scoping review

Crimean-Congo hemorrhagic fever virus(CCHFV) is responsible for widespread tick-borne zoonotic viral disease CCHF in African, Middle Eastern, Asian, and European countries. CCHFV can be spread to humans through tick bites or contact with infected animals or humans, and it often progresses from asymptomatic to severe/lethal illness, with fatality rates ranging from 10% to 40% in humans. Today, CCHF is growing into a significant public health concern due to its very high prevalence, severity of the condition, and lack of available vaccines and specific treatments. Recent research has been drawn towards a more accurate study of CCHFV characteristics, including the structure, genetic diversity, mechanisms involved in pathogenesis and immunopathogenesis, and clinical features. In addition, the use of animal models(mouse and non-human primates) and advanced diagnostic tools in recent years has resulted in a significant advance in CCHF related studies. In this context, we summarized the latest findings about CCHF research, its health complications, animal models, current diagnosis, vaccination, and CCHF treatments, and therapeutic strategies. Furthermore, we discussed existing deficiencies and problems in CCHFV analysis, as well as areas that still need to yield conclusive answers.

Porcine Circovirus 2:Immunopathogenesis and Recent Developments in Vaccines

Porcine circovirus 2 (PCV2) is currently considered an important etiologic agent of swine and its infection has potentially serious economic impact on the swine industry worldwide. This virus is frequently associated with postweaning multisystemic wasting syndrome (PMWS), and also with other clinical conditions such as porcine dermatitis and nephropathy syndrome (PDNS), late-term abortions, reproductive failure in sows, proliferative and necrotizing pneumonia and congenital tremors. The term porcine circovirus-associated disease (PCVAD) is currently used to refer to any of these diseases when they are associated with PCV2 infection. The PCV2 was recognized as a pathogen in 1997, and many questions regarding its biology and pathogenesis remain unanswered. Currently, some studies have shown the production of new vaccine candidates and field efficacy testing of commercial vaccines. This review discusses some major points concerned with immunopathogenesis and vaccines for PCV2 infection.

Immunopathogenesis and immunomodulatory therapy for myocarditis

Myocarditis is an inflammatory cardiac disease characterized by the destruction of myocardial cells, infiltration of interstitial inflammatory cells, and fibrosis, and is becoming a major public health concern. The aetiology of myocarditis continues to broaden as new pathogens and drugs emerge. The relationship between immune checkpoint inhibitors, severe acute respiratory syndrome coronavirus 2, vaccines against coronavirus disease-2019, and myocarditis has attracted increased attention. Immunopathological processes play an important role in the different phases of myocarditis, affecting disease occurrence, development, and prognosis. Excessive immune activation can induce severe myocardial injury and lead to fulminant myocarditis,whereas chronic inflammation can lead to cardiac remodelling and inflammatory dilated cardiomyopathy. The use of immunosuppressive treatments, particularly cytotoxic agents, for myocarditis, remains controversial. While reasonable and effective immunomodulatory therapy is the general trend. This review focuses on the current understanding of the aetiology and immunopathogenesis of myocarditis and offers new perspectives on immunomodulatory therapies.

A Review of Hepatitis B Virus and Hepatitis C Virus Immunopathogenesis

Despite the advances in therapy,hepatitis B virus(HBV)and hepatitis C virus(HCV)still represent a significant global health burden,both as major causes of cirrhosis,hepatocellular carcinoma,and death worldwide.HBV is capable of incorporating its covalently closed circular DNA into the host cell’s hepatocyte genome,making it rather difficult to eradicate its chronic stage.Successful viral clearance depends on the complex interactions between the virus and host’s innate and adaptive immune response.One encouraging fact on hepatitis B is the development and effective distribution of the HBV vaccine.This has significantly reduced the spread of this virus.HCV is a RNA virus with high mutagenic capacity,thus enabling it to evade the immune system and have a high rate of chronic progression.High levels of HCV heterogeneity and its mutagenic capacity have made it difficult to create an effective vaccine.The recent advent of direct acting antivirals has ushered in a new era in hepatitis C therapy.Sustained virologic response is achieved with DAAs in 85–99%of cases.However,this still leads to a large population of treatment failures,so further advances in therapy are still needed.This article reviews the immunopathogenesis of HBV and HCV,their properties contributing to host immune system avoidance,chronic disease progression,vaccine efficacy and limitations,as well as treatment options and common pitfalls of said therapy.

Cellular and Molecular Immunopathogenesis of Ulcerative Colitis

Ulcerative colitis （UC） is an inflammatory disease of the rectal and colonic mucosa and seems to result from a complex series of interactions between susceptibility genes, the environment and the immune system. Various components of the mucosal immune system are implicated in the immunopathogenesis of UC. Evidence from animal models also suggests that an altered immune response to the commensal microflora of the host plays a central role in the development of UC. So in this review, we elucidate the cells and molecules which are implicated in the immunopathogenesis of the disease from four aspects： antigens in the intestine, dendritic cells, toll like receptors and NF-κB in the UC.

Human leukocyte antigens-immunogenetics of neuromyelitis optica or Devic’s disease and the impact on the immunopathogenesis,diagnosis and treatment:a critical review

Neuromyelitis optica(NMO)is an autoimmune demyelinating disorder,predominantly characterized by severe optic neuritis,transverse myelitis and the high level of antibodies against aquaporin-4(AQP4)or NMO-immunoglobulin G(IgG).Researches trying to correlate NMO with specific human leukocyte antigen(HLA)alleles took place in a limited extend in the last few years.Nevertheless,it has become clear that HLAs play a crucial role in the genetic risk of NMO,in the understanding of its pathogenesis and the differential diagnosis mainly from multiple sclerosis(MS),and also from other demyelinating diseases.In this study,we retrieved all the available data in the MEDLINE concerning the distribution of HLA frequencies in NMO and NMO-spectrum diseases,in all available ethnic groups,and compared them with those of MS.The results suggest that,the well-established HLA-DRB1*15:01 allele,associated with MS,plays rather a protective role for NMO.HLA-DRB1*03 allele is highly frequent in the NMO-IgG positive Caucasian patients,while HLA-DPB1*05:01 is the predominant allele in Japanese patients.The HLA-genotype and anti-AQP4 presence are the common immunological components in cases of comorbidity of NMO and other autoimmune diseases.The authors aim to summarize in the critical review the results of these researches worldwide,create a workable table including all this information for an easier reading approach and highlight the importance of these results in therapeutic decision making,using the HLA profile as biomarker in patients’stratification.

Is there a window of opportunity for the therapeutic use of vitamin D in multiple sclerosis?

Multiple sclerosis is an autoimmune treatable but not curable disease.There are a multiplicity of medications for multiple sclerosis therapy,including a class entitled disease-modifying drugs that are mainly indicated to reduce the number and severity of disease relapses.Not all patients respond well to these therapies,and minor to severe adverse effects have been reported.Vitamin D,called sunshine vitamin,is being studied as a possible light at the end of the tunnel.In this review,we recapitulated the similar immunopathogenesis of multiple sclerosis and experimental autoimmune encephalomyelitis,the immunomodulatory and neuroprotective potential of vitamin D and the state-of-art concerning its supplementation to multiple sclerosis patients.Finally,based on our and other groups’experimental findings,we analyzed the need to consider the relevance of the route and the different time-point administration aspects for a more rational indication of this vitamin to multiple sclerosis patients.

Adaptive immunity in the liver

The anatomical architecture of the human liver and the diversity of its immune components endow the liver with its physiological function of immune competence. Adaptive immunity is a major arm of the immune system that is organized in a highly specialized and systematic manner, thus providing long-lasting protection with immunological memory. Adaptive immunity consists of humoral immunity and cellular immunity. Cellular immunity is known to have a crucial role in controlling infection, cancer and autoimmune disorders in the liver. In this article, we will focus on hepatic virus infections, hepatocellular carcinoma and autoimmune disorders as examples to illustrate the current understanding of the contribution of T cells to cellular immunity in these maladies. Cellular immune suppression is primarily responsible for chronic viral infections and cancer. However, an uncontrolled auto-reactive immune response accounts for autoimmunity. Consequently, these immune abnormalities are ascribed to the quantitative and functional changes in adaptive immune cells and their subsets, innate immunocytes, chemokines, cytokines and various surface receptors on immune cells. A greater understanding of the complex orchestration of the hepatic adaptive immune regulators during homeostasis and immune competence are much needed to identify relevant targets for clinical intervention to treat immunological disorders in the liver.

Hepatobiliary Schistosomiasis

Schistosomiasis is an ancient parasitic disease that has afflicted Egyptians since the time of the pharaohs.The disease is caused by lodged schistosome eggs in the host liver,evoking an immune response and leading in some patients to the development of hepatic granuloma and fibrosis.Here,we review the epidemiology,immunopathogenesis,and clinical profile of schistosomiasis.This information may aid in the development of more efficacious treatments and improved disease prognosis.