Overview of the immunological mechanisms in hepatitis B virus reactivation:Implications for disease progression and management strategies

Hepatitis B virus(HBV)reactivation is a clinically significant challenge in disease management.This review explores the immunological mechanisms underlying HBV reactivation,emphasizing disease progression and management.It delves into host immune responses and reactivation’s delicate balance,spanning innate and adaptive immunity.Viral factors’disruption of this balance,as are interac-tions between viral antigens,immune cells,cytokine networks,and immune checkpoint pathways,are examined.Notably,the roles of T cells,natural killer cells,and antigen-presenting cells are discussed,highlighting their influence on disease progression.HBV reactivation’s impact on disease severity,hepatic flares,liver fibrosis progression,and hepatocellular carcinoma is detailed.Management strategies,including anti-viral and immunomodulatory approaches,are critically analyzed.The role of prophylactic anti-viral therapy during immunosuppressive treatments is explored alongside novel immunotherapeutic interventions to restore immune control and prevent reactivation.In conclusion,this compre-hensive review furnishes a holistic view of the immunological mechanisms that propel HBV reactivation.With a dedicated focus on understanding its implic-ations for disease progression and the prospects of efficient management stra-tegies,this article contributes significantly to the knowledge base.The more profound insights into the intricate interactions between viral elements and the immune system will inform evidence-based approaches,ultimately enhancing disease management and elevating patient outcomes.The dynamic landscape of management strategies is critically scrutinized,spanning anti-viral and immunomodulatory approaches.The role of prophylactic anti-viral therapy in preventing reactivation during immunosuppressive treatments and the potential of innovative immunotherapeutic interventions to restore immune control and proactively deter reactivation.

Efficacy of Telbivudine in the Treatment of Chronic Hepatitis B and Liver Cirrhosis and Its Effect on Immunological Responses

This study was aimed to evaluate the long-term effects of telbivudine（Ld T） in the treatment of chronic hepatitis B（CHB） and HBV-related liver cirrhosis（LC） and to observe the changes of immunological responses during Ld T treatment. Clinical data of 80 CHB and 28 HBV-related LC patients who were administered with Ld T for 108 weeks and followed up were retrospectively analyzed. The liver function indicators including ALT, AST and γ-GT, HBV DNA copy number in serum and the rates of hepatitis B e antigen（HBe Ag） seroconversion were analyzed before and 12, 24, 36, 48, 60, 72, 84, 96 and 108 weeks after Ld T treatment in CHB and LC groups. Four serum fibrosis-related markers, including hyaluronic acid（HA）, human laminin（LN）, human type Ⅳ collagen（Ⅳ-C） and human N-terminal procollagen Ⅲ peptide（PC-Ⅲ）, were detected before and after Ld T treatment in LC group. The results showed favorable viral suppression and biochemical responses after treatment with Ld T for 12 weeks, and a high rate of virological and biochemical control was maintained during the course of 108-week treatment in both CHB and LC groups. The four fibrosis-related markers, especially HA and LN, were down-regulated to some degrees in LC group. Moreover, Ld T treatment led to the fluctuation of the circulating interferon-γ（IFN-γ） and interleukin-10（IL-10） levels at different time points in CHB group. It was concluded that Ld T could favorably lead to the virological suppression and biochemical remission. Besides, IFN-γ and IL-10 may represent a suitable and effective predictor of responsiveness during Ld T therapy.

A Study of Immunological Indices for Diagnosis of Chronic Berylliosis

The results of the Be-induced leukocyte migration inhibition test(Be-MIT),the lymphocyte transformation test(LI),the E-rosette formation test(E-RFC),the old tuberculin test(OT),and sero-immunoglobulin(IgG,IgA,IgM)measurements on 13 cases of berylliosis,44 members of the observation group,and 51 members of the contact group are rèported.In the Be-MIT,2 of the berylliosis patients were new cases that had been diagnosed and treated for a long time,and both tested positive(18%).Fourteen patients from the observation group tested positive(32%), and 15 from the contact group tested positive(30%).The 8 cases in the control group tested negative;7 patients from the observation group and 3 of the berylliosis cases tested negative after being treated.The lymphocyte transformation rates of the observation group and the berylliosis group were significantly lower than that of the control group(P<0.01).Both Et-RFC and Ea- RFC contents in the group with berylliosis were much lower than those in the control group(P <0.01).OT tests were performed on 8 berylliosis patients and 10 healthy men.Seven patients showed negative reactions and one showed a positive reaction.All the healthy men showed positive reactions.The IgG and IgA levels of the observation group were significantly higher than those of the control group(P<0.01).The Be-MIT could detect active beryllium disease at an early stage as well as Be-sensitive individuals.This test could be used as a supplementary diagnostic index for the differential diagnosis of berylliosis and for the evaluation of a curative effect.1989 Academic Press,Inc.

Inhibitory effect of cyclosporin A on the immunological rejection of rats with cerebral hemorrhage following transplantation of nerve growth factors transfected glial cells

BACKGROUND： At present, it has been confirmed that immunological rejection exists in the cell transplantation in brain tissue, the effects of immunosuppressant on the immunological rejection and the survival of grafts in brain cell transplantation are worthy being investigated further. OBJECTIVE： To observe the immunological rejection after transgeneic cell transplantation in treating cerebra hemorrhage in rats, and investigate the interventional effect of cyclosprin. DESIGN ： A randomized controlled study SETTINGS： Second Affiliated Hospital of Xuzhou Medical College; First Affiliated Hospital of Nanjing Medica University. MATERIALS： Thirty-five healthy clean-degree SD rats of 6-8 weeks old were used, weighing 200-250 g, either male or female; The FACSort flow cytometer （American BD Company） and NYD-1000 image analytical system were used, The rat-anti-rat CD4 monoclonal antibody, rat-anti-rat CD8 monoclonal antibody, and rat-anti-rat MHC Ⅱ antigen monoclonal antibody were purchased from Santa Cruz Company; SP and DAB kits were purchased from Beijing Zhongshan Bio-engineering Company. XSP-8C2 light microscope was the product of Shanghai Zousun Optical Instrument, Co.,Ltd, and KYKY-3800B electron microscope was the product of China KYKY Technology Development Co.,Ltd. METHODS ： The experiments were carried out in the animal experimental center of Nanjing Medical University from April to July in 2003. ① Model establishment： The rats were anesthetized, and then the coordinates of left internal capsule were identified, and the needle was withdrawn after 120 μL blood was injected into the internal capsule. Adenoviruses were taken as the carriers, after the astrocytes were successfully transfected by nerve growth factor（NGF） gene, 0.2 mL cell suspension was injected into the sites of cerebral hemorrhage. Thirty successfully established rat models were randomly divided into cyclosporin A group （n=18） and control group, the rats were treated with intraperitoneal injection of cyclosporin A （10 mg/kg per day） intraperitoneal injection of saline of the same dosage from the 1^st day after transplantation, once a day for 7 days continuously.② CD4^＋ and CD4^＋ detection： The CD4^＋ and CD4^＋ T lymphocytes in caudal vein were counted with flow cytometer at 15 days after treatment. ③ Morphological observation in the transplanted sites： The rats were killed and then brain tissues were taken out, the transplanted sites and the structure of the normal brain tissue around the transplanted sites were observed with light and electron microscopes. ④Detections of the infiltration of T lymphocyte subsets and expression of major histocompatibility complex （MHC） Ⅱ antigen in the transplanted sites： The image analysis of immunohistochemical sections was performed with the image analytical system, and the integral optical density （IOD） was taken as the statistical value to observe the infiltration of T lymphocyte subsets and expression of MHC Ⅱ antigen in the transplanted sites, and the normal brain tissue around the transplanted sites were taken as controls. MATN OUTCOME MEASURES： ① Countings of CD4^＋ and CD4^＋ in peripheral blood; ②Results of the morphological observation in the transplanted sites; ③ Infiltration of T lymphocyte subsets and expression of MHC Ⅱ antigen in the transplanted sites RESULTS ： Totally 35 rats were used, and 30 were successfully made into models, 5 died during the treatment, the other 25 were involved in the analysis of results. ① Results of CD4^＋ and CD4^＋ T lymphocytes in pedpherel blood： The percentages of CD4^＋ and CD4^＋ T lymphocytes in the cyclosporin A group were （29.20±3.97）% and （20.65±2,02）%, respectively, which were obviously lower than those in the control group [（47,39±3,01）%, （28.30±2.36）%, t=-4.983, 4.012, P 〈 0.05], and the CDC/CD4^＋ ratio was obviously lower than that in the control group （1,41±0.86, 1,64^＋0.69, t=-3. 871, P〈 0.05）.② Morphological results in the transplanted sites： Under optical and electron microscopes, the survival region of the transplant was round, and it had an unobvious migration region with the normal brain tissues, the grafts had normal cellular form. Infiltrations of lymphocytes and monocytes were observed in both groups, and mainly located in the transplanted sites, and the expression of lymphocytes in the cyclosporin A group was markedly lower than that in the control group, and no above-mentioned changes were observed in the normal brain tissue around the transplanted sites. ③ Results of CD. and CD4^＋ T lymphocytes and expression of MHC Ⅱ antigen in the transplanted sites： The CD4^＋ and CD4^＋ T lymphocytes and expression of MHC Ⅱ antigen in the transplanted sites were observed in both groups. The IOD of CD4^＋ and CD4^＋ antigen positive cells in the cyclosporin A group were obviously lower than those in the control group （1.85±0.38, 1.44^＋0.33; 3.33±0.37, 2.648±0.56, /=-4.122, 4.434, P〈 0.05）, and the IOD of MHC Ⅱantigen positive cells was markedly lower than that in the control group （0.76±0.22, 0.94±0.24, t=3.885, P 〈 0.05）. CONCLUSION： There is immunological rejection in brain tissue after the transplantation of NSC transgeneic glial cells. ② The immunosuppressant of cyclosporin A can reduce the immunological rejection after the cell transplantation.

Radiation Effects on the Immunological Functions and Membranes of Alveolar Macrophages of Rats

Alveolar macrophages (AM) from BCG activated Wistar rat were irradiated with different doses of Gamma rays in vitro. The effects of radiation on their immunological functions and membrane damage were studied. The non-specific cytotoxicity and specific phagocytosis of AM irradiated with dose of 0, 100, 300 and 500 Gy decreased with the increase in dose. The relative fractions of Lactate Dehydrogenase and Beta-glucuronidase (β-glu) activity in supernatant increased with the increase in dose. There was a correlation between the suppression of immunological functions and the degree of damage of cytoplasmic and lysosomal membranes of AM after irradiation. Na2SeO3, a protective agent of cell membranes, alleviated this effect on the suppressive cytotoxicity indices of irradiated AM.

Effect of Glycyrrhiza uralensis Fisch polysaccharide on growth performance and immunologic function in mice in Ural City,Xinjiang

Objective:To discuss the effect of Glycyrrhiza uralensis(G.uralensis) Fisch polysaccharide on growth performance and immunologic function in mice in Ural City,Xinjiang and to provide important data supporting the application of Glycyrrhiza polysaccharide.Methods:A total of100 Kunming mice aged 3 weeks old were randomly divided into 5 groups with 20 mice in each group(10 were females and 10 were males).About 0.5 mL normal saline was given to the mice of control group every day and 0.5 mL G.uralensis Fisch polysaccharide was given to the mice of other groups at the concentration of 1,20,50 and 100 mg/mL respectively.The growth performance(average body weight,average daily feed intake and feed efficiency),immune organ indexes(spleen index and thymus index) and immunologic function(serum IL-2,CD4^+/CD8^+ and the activity of NK cells) of mice in each group were detected continuously.Results:The average body weight,feed efficiency,serum IL-2,CD4^+/CD8^+ and the activity of NK cells of mice were increased with the increase of administrated time after administrating G.uralensis Fisch polysaccharide and were reached up the largest level on Day 28.At the same time,each index was proportional to the given dose and was significantly higher than those of control group and reached up the largest level at the administrated dose of 100 mg/mL.After administrating G.uralensis Fisch polysaccharide,the spleen index and thymus index of mice were increased with the increase of administrated dose and the spleen index and thymus index of mice administrated with the dose of 100 mg/mL were maximum which was more than 1.51 times and 1.43 times of that in control group respectively and the comparative differences showed statistical significance(P<0.05).The average daily feed intake of mice in each group was increased with the passage of lime and at the same time,the comparison of average daily feed intake of mice in each group was not significantly different(P>0.05).Conclusions:G.uralensis Fisch polysaccharide can significantly improve the growth performance and immunologic function of mice and laid a research basis for the clinical application of G.uralensis Fisch polysaccharide.

Traditional Chinese Medicine Compound Mianbu Mixfang Is Effective in Treating Immunological Infertility: a Female Mice

Objective To study the therapeutic effectivess of Traditional Chinese Medicine compound mixture Mianbu Fang (Immunological infertility therapy) on immunological infertility caused by antisperm antibody (AsAb) in female mice. Materials & Methods Forty-two female Kunming mice were evenly divided into 7 groups by weight. Group A was control group; Group B was model of infertility. Group C, D and E were fed with normal, half and double dosage of Mianbu I respectively. Group F and G were fed with Mianbu II and prednisone Acetates respectively. Animal model of immunological infertility were set up by injecting mice sperm to the other 36 Kunming female mice except Group A. The AsAb levels in serum, cervical mucus were measured, the histological and immunohistochemistry changes in ovary and endometrium were observed, and the pregnancy indexes were compared in different groups. Results Compared with the infertility model group, the AsAb level in serum and cervical mucus in treatment group was lower. Less immune compounds in ovary and endometrium and atretic follicle of ovary was found in treatment group than in model and control group. The immune compounds in ovary and endometrium were less in the treatment group than that in the model and control group. Conclusion By regulating immunological system, Traditional Chinese Medicine compound mixfang Mianbu Fang lowers AsAb in the circulation system and special organs, eliminates immunological compound, repairs tissue impairment and increases pregnancy of female mice.

Ocular diseases: immunological and molecular mechanisms

Many factors, such as environmental, microbial and endogenous stress, antigen localization, can trigger the immunological events that affect the ending of the diverse spectrum of ocular disorders. Significant advances in understanding of immunological and molecular mechanisms have been researched to improve the diagnosis and therapy for patients with ocular inflammatory diseases. Some kinds of ocular diseases are inadequately responsive to current medications;therefore, immunotherapy may be a potential choice as an alternative or adjunctive treatment, even in the prophylactic setting. This article first provides an overview of the immunological and molecular mechanisms concerning several typical and common ocular diseases; second, the functions of immunological roles in some of systemic autoimmunity will be discussed; third, we will provide a summary of the mechanisms that dictate immune cell trafficking to ocular local microenvironment in response to inflammation.

EFFECT OF ACUPUNCTURE AND POINT-INJECTION TREATMENT ON IMMUNOLOGIC FUNCTION IN RHEUMATOID ARTHRITIS

The results of treatment of 54 cases of rheumatoid arthritis(RA)by warm needling(WN)and point-injection(PI)with Zhuifengsu are reported.Good clinical results were observedwith an effective rate of 100%.At the same time,changes in cellular and humoral immunityand other parameters in peripheral blood were noted before and after treatment.The NK ac-tivity and IL-2 value in RA patients were found to be lower than those of normalindividuals;both increased after treatment(P【0.01).This suggests that the WN and PIwith Zhuifengsu exert a regulatory effect on the cellular immunological function.

New insights into the immunologic role of oligodendrocyte lineage cells in demyelination diseases

Oligodendrocyte lineage cells(OL-lineage cells)are a cell population that are crucial for mammalian central nervous system(CNS)myelination.OL-lineage cells go through developmental stages,initially differentiating into oligodendrocyte precursor cells(OPCs),before becoming immature oligodendrocytes,then mature oligodendrocytes(OLs).While the main function of cell lineage is in myelin formation,and increasing number of studies have turned to explore the immunological characteristics of these cells.Initially,these studies focused on discovering how OPCs and OLs are affected by the immune system,and then,how these immunological changes influence the myelination process.However,recent studies have uncovered another feature of OL-lineage cells in our immune systems.It would appear that OL-lineage cells also express immunological factors such as cytokines and chemokines in response to immune activation,and the expression of these factors changes under various pathologic conditions.Evidence suggests that OL-lineage cells actually modulate immune functions.Indeed,OL-lineage cells appear to play both"victim"and"agent"in the CNS which raises a number of questions.Here,we summarize immunologic changes in OL-lineage cells and their effects,as well as consider OL-lineage cell changes which influence immune cells under pathological conditions.We also describe some of the underlying mechanisms of these changes and their effects.Finally,we describe several studies which use OL-lineage cells as immunotherapeutic targets for demyelination diseases.

Functional and immunological peculiarities of peripheral nerve allografts

This review addresses the accumulating evidence that live(not decellularized)allogeneic peripheral nerves are functionally and immunologically peculiar in comparison with many other transplanted allogeneic tissues.This is relevant because live peripheral nerve allografts are very effective at promoting recovery after segmental peripheral nerve injury via axonal regeneration and axon fusion.Understanding the immunological peculiarities of peripheral nerve allografts may also be of interest to the field of transplantation in general.Three topics are addressed:The first discusses peripheral nerve injury and the potential utility of peripheral nerve allografts for bridging segmental peripheral nerve defects via axon fusion and axon regeneration.The second reviews evidence that peripheral nerve allografts elicit a more gradual and less severe host immune response allowing for prolonged survival and function of allogeneic peripheral nerve cells and structures.Lastly,potential mechanisms that may account for the immunological differences of peripheral nerve allografts are discussed.

Histology and Immunohistochemistry Study on Mianbu Fang Healing Immunological Infertility of Male Mice

To observe the histological and immunohistochemical changes caused by of Traditional Chinese Medicine——Mianbu Fang (Immunological Infertility Healing Mixture) in testis and epididymus of male mice with immunological infertility induced by antisperm antibody (AsAb). Materials & Methods Models of mice with immunological infertility were used by injection of mice sperm. These mice were treated with Mianbu Ⅰ, Mianbu Ⅱ or Prednisone Acetates. The characteristics on histology and immunohistochemistry of mice were analyzed. Results High level of AsAb was detected in serum and seminal vesicle plasma of model mice after treatment. Immune compounds mostly deposited in limiting membrane of seminiferous tubules, spermatogonium and epithelia of epididymis ducts. The number of spermatogenic cells per convoluted seminiferous tubule decreased. However, the Chinese medicine could significantly reduce the level of AsAb, or even eliminate the antibodies and clear out the immune compounds and increase the number of spermatogenic cells of seminiferous tubules. Conclusion Chinese Medicine Mianbu Ⅰand Ⅱ can regulate, absorb and clear out circulation and partial AsAb, as well as immunological compound. Hence, they can increase the number of spermatogenic cells of seminiferous tubules and increase the pregnancy of mice.

Autoimmune pancreatitis and pancreatic cancer:Epidemiological aspects and immunological considerations

Ordinary chronic pancreatitis is a well-known risk factor for pancreatic cancer,whereas such an association with autoimmune pancreatitis(AIP)is widely debated.Due to the rarity of the latter disorder,there are few specific clinical and epidemiological studies investigating the relation between AIP and pancreatic cancer,which do not seem to support it.However,these studies are affected by several limitations and,therefore,a link between AIP(and,specifically,type 1 AIP)and pancreatic cancer cannot be ruled out definitively on this basis.Moreover,several immunopathological aspects of type 1 AIP and,in general,immunoglobulin G4-related disease can create an immunological context that may impair the tumoral immunosurveillance and promote the pancreatic carcinogenesis and its progression.In detail,Th2 immunological dominance,type 2 macrophage polarization and basophil infiltration observed in type 1 AIP,may play a permissive role in creating a favorable immunological environment for pancreatic carcinogenesis,in addition to the immunosuppressive therapies that can be used in these patients.

CXCL16 participates in pathogenesis of immunological liver injury by regulating T lymphocyte infiltration in liver tissue

AIM: To investigate the role of CXCL16 in the pathogenesis of immunological liver injury and to explore the possible mechanism of T lymphocyte infiltration requlated by CXCL16.METHODS: Immunological liver injury in murine model was induced by Bacille Calmette-Guerin and lipopolysaccharide.Expression pattem and distribution of CXCL16 were examined by real-time quantitative RT-PCR and immunohistochemical analysis. Anti-CXCL16 antibody was administrated in vivo to investigate its effect on T-cell recruitment and acute hepatic necrosis. The survival of murine model was also evaluated.RESULTS: The murine immunological liver injury model was successfully established. CXCL16 expression increased and predominantly distributed in periportal areas and vascular endothelia in injured liver tissues. Administration of anti-CXCL16 Ab protected the mice from death and acute liver damage. Approximately 70% of the mice survived for 72 h in the anti-CXCL16 Ab treatment group, whereas 80% died within 72 h in control Ab group. The number of liver-infiltrating T lymphocytes was significantly reduced from 1.01×L07 to 3.52x 106/liver, compared with control Ab treatment.CONCLUSION: CXCL16 is involved in immunological liver injury by regulating T lymphocyte infiltration in liver tissue.

Hepatitis C virus lymphotropism and peculiar immunological phenotype:Effects on natural history and antiviral therapy

Hepatitis C virus(HCV) has been recognized to be both a hepato-and lymphotropic virus.HCV lymphotropism represents an essential lap in the pathogenesis of virusrelated autoimmune and lymphoproliferative disorders,ranging from clonal expansion of B-cells with organ-and non-organ-specific autoantibody production up to overt non-Hodgkin's lymphoma along a continuous step-by-step model of B-cell lymphomagenesis,where the intermediated mixed cryoglobulinemia could be considered as a stage of suppressible antigen-driven lymphoproliferation.HCV infection of lymphoid cells could set up privileged reservoirs able to interfere with the host viral clearance eff iciency and may be implicated in viral recurrence after apparently successful antiviral therapy.The HCV long-lasting extrahepatic replicative state generates an abnormal systemic immunological response,easily detectable by searching simple laboratory and clinical parameters,mainly represented by vasculitis-like skin features and hypocomplementemia.The presence or absence of this hypersensitivity pattern seems to correlate with the antiviral response and could be identif ied as a novel immunological cofactor.Further research is required to fully verify the real impact on therapeutic choice/regimen.

Effect of Yanhuning in combined with azithromycin on the inflammatory cytokines and immunological function in children with mycoplasma pneumonia

Objective: To explore the effect of Yanhuning in combined with azithromycin on the inflammatory cytokines and immunological function in children with mycoplasma pneumonia. Methods: A total of 130 children with mycoplasma pneumonia were included in the study and randomized into the treatment group (n=65) and the control group (n=65). The patients in the control group were given azithromycin. On the above basis, the patients in the treatment group were given Yanhuning. The patients in the two groups were continuously treated for 7 d. The levels of serum inflammatory cytokines and immunological function indicators before and after treatment in the two groups were detected and compared. Results: When compared with before treatment, the serum IL-2 level after treatment in the two groups was significantly elevated, while IL-4, IL-10, IL-13, IL-6, TNF-α, and IFN-γ levels were significantly reduced;moreover, the improvement in the treatment group was significantly superior to that in the control group. When compared with before treatment, CD3+, CD4+, and CD4+/CD8+ after treatment in the two groups were significantly elevated, and those in the treatment group were significantly higher than those in the control group, while CD8+ was significantly reduced, but the comparison between the two groups was not statistically significant. When compared with before treatment, RBC-C3bR after treatment in the two groups was significantly elevated, while RBC-ICR was significantly reduced;moreover, the improvement in the treatment group was significantly superior to that in the control group. Conclusions: Yanhuning in combined with azithromycin in the treatment of mycoplasma pneumonia in children can significantly enhance the immunological function, and reduce the inflammatory reaction, with an effect significantly superior to that by single application of azithromycin.