氢化考的松对大鼠垂体及胃肠道ACTH免疫反应性细胞的影响

用过氧化物酶抗过氧化酶免疫组织化学方法研究氢化考的松对大鼠垂体及胃肠道促肾上皮质激素免疫反应性（ａｄｒｅｎｏｃｏｒｔｉｃｏｒｔｒｏｐｈｉｃｈｏｍｏｎｅｉｍｍｕｎｏｒｅａｃｔｉｖｉｔｙ，ＡＣＴＨ－ＩＲ）细胞的影响，结果表明，注射氢化考的松，大鼠垂体前叶和十二指肠近端粘膜ＡＣＴＨ－ＩＲ细胞免疫的反应性减弱，细胞数量减少，尤以垂体前叶细胞更敏感。

枫蓼肠胃康颗粒对细胞免疫反应性结肠炎中SOD、MDA的影响

目的 观察枫蓼肠胃康颗粒对细胞免疫反应性结肠炎大鼠血中超氧化物歧化酶 (SOD)和丙二醛 (MDA)的作用。方法 将雄性Wistar大鼠分成 6组 ,用三硝基苯磺酸和ethanol混和液灌肠法 ,建立大鼠细胞免疫反应性结肠炎动物模型 ,在 1、3、7、2 1d分别处死大鼠。对肠壁形态进行观察 ,并测定大鼠血中SOD活力及MDA含量。结果 高剂量组的肠壁损伤分值在 7、2 1d较造模组降低 (P <0 0 5 ) ;造模组大鼠SOD活力d 3和d 7低于高剂量给药组 (P <0 0 5 ) ,MDA含量d 7、2 1高于各给药组 (P <0 0 1或P <0 0 5 )。

过敏性哮喘中Th2免疫反应的作用和相关机制

哮喘是多种细胞及细胞组分参与的慢性气道炎症,常伴有广泛而多变的气流阻塞,一般可自行或通过治疗逆转。过敏性哮喘主要是由辅助性T细胞2(Th2)介导的免疫反应。当变应原进入机体后,免疫细胞被激活,导致多种细胞因子募集和释放。由细胞因子导致的免疫功能紊乱受到了越来越多的关注,细胞因子基因剔除或过表达,对疾病的发生和发展产生不同的影响。明确Th2免疫反应机制在过敏性哮喘中的作用,可为过敏性哮喘的诊断和针对Th2细胞信号转导开发治疗过敏性哮喘的新药提供相应的理论基础。

Distribution of Oxytocin Hypothamic-Picuitary-Ovary Axis in Guangxi Local Buffalo

To study the association of oxytocin (OT)'s distribution in hypothalamatic,pituitary and ovary,and understand how the OT secrete releasing in hypothalamus,pituitary and ovaries,the paraffin section immunohistochemistry SuperPicTureTM two step method was used to detect the distribution of OT in hypothalamatic-pituitary-ovary axis of five femal Guangxi local buffalo. The test results could provide morphology according to study the OT's synthesis and mechanism of action,and could play reference and directions part in breeding Guangxi local buffalo. The test results display:oxytocin immuno reactive (OT-IR) neuronsw eremainly distributed arcuate nucleus,supraoptic nucleus and paraventricular nucleus,and OT-IR neurons was also found in ventromedial nucleus,ventrolateralis nucleus,suprachiasmaticus nucleus,dorsomedial nucleus,mamillary body,anterior hypothalamic nucleus and so on. The OT immunoactive production was found in pituitary and few OT-IR nerve fibers extended to post pituitary from hypophyseal stalk and medium eminence. In ovaries,OT immunoactive productions were only distributed in germinal epithelium cells,granulosa cells and lutein cells. The OT was first discovered in singulorum link of hypothalamatic-pituitary-ovary axis of Guangxi local buffalo. The OT immunoactive neurons were first discovered in every main nucleus of Guangxi local buffalo hypothalamus,especially distributed in arcuate nucleus,supraoptic nucleus and paraventricular nucleus.

白色念珠菌感染与口腔癌的关系

口腔癌是头颈部最常见的癌症之一,严重影响患者生存质量和生活水平。白色念珠菌是口腔中最常见的机会性致病真菌,当宿主免疫功能低下时表现出致病性,容易引起念珠菌感染。近年来研究发现白色念珠菌感染与口腔癌关系密切,本文对口腔癌患者白色念珠菌感染的流行病学特点,以及白色念珠菌感染对口腔癌发生发展的影响及其机制研究进行综述。通过回顾相关文献发现:口腔癌患者白色念珠菌感染风险增加,白色念珠菌感染可能通过损伤口腔上皮、产生致癌物质、触发慢性炎症及辅助性T细胞17免疫反应等机制促进口腔癌的发生发展。然而目前这些机制的研究仍比较表浅,缺乏充足的直接证据,未来仍需进行大量研究,以期进一步明确白色念珠菌的促癌机制,为防治口腔癌提供新思路。

Assays for predicting and monitoring responses to lung cancer immunotherapy

Immunotherapy has become a key strategy for cancer treatment, and two immune checkpoints, namely, programmed cell death 1 （PD-1） and its ligand （PD-L1）, have recently emerged as important targets. The interaction blockade of PD-1 and PD-L1 demonstrated promising activity and antitumor efficacy in early phase clinical trials for advanced solid tumors such as non-small cell lung cancer （NSCLC）. Many cell types in multiple tissues express PD-L1 as well as several tumor types, thereby suggesting that the ligand may play important roles in inhibiting immune responses throughout the body. Therefore, PD-L1 is a critical immunomodulating component within the lung microenvironment, but the correlation between PD-L1 expression and prognosis is controversial. More evidence is required to support the use of PD-L1 as a potential predictive biomarker. Clinical trials have measured PD-L1 in tumor tissues by immunohistochemistry （IHC） with different antibodies, but the assessment of PD-L1 is not yet standardized. Some commercial antibodies lack specificity and their reproducibility has not been fully evaluated. Further studies are required to clarify the optimal IHC assay as well as to predict and monitor the immune responses of the PD-I/PD-L1 pathway.

白色念珠菌影响口腔黏膜癌变的机制进展

微生物感染是癌症发生的重要因素,目前,越来越多的研究支持这样的观点:机会性白色念珠菌通过患者的免疫抑制状态,增加患者患癌的概率和肿瘤转移的风险。最近的研究结果表明,白色念珠菌可能通过以下几种机制来促进癌症发生:产生致癌副产物、引发炎症以及诱导辅助性T细胞17反应。本文就白色念珠菌影响口腔黏膜癌变机制的研究进展作一综述,以期能够进一步阐明白色念珠菌和癌症发生之间的关系,有望为预防和治疗口腔黏膜癌变提供新思路。

嗜碱性粒细胞在支气管哮喘中的作用

嗜碱性粒细胞是一类长期被忽略的免疫细胞,近期因其在2型辅助性T淋巴细胞(Th)免疫应答中的重要作用而被关注。嗜碱性粒细胞通过多种可能机制参与支气管哮喘(哮喘)发病。嗜碱性粒细胞作为始动者通过与树突状细胞相互作用启动和建立Th2免疫应答;作为免疫调节者,通过分泌白细胞介素4等细胞因子调节2型天然淋巴细胞等免疫细胞功能,进而巩固变态反应性炎症;作为效应者,通过IgE和非IgE途径活化嗜碱性粒细胞直接参与气道变态反应性炎症。利用嗜碱性粒细胞活化状态作为生物标志物监测变态反应性疾病治疗转归是目前临床研究热点,对实现哮喘个体化治疗有重要临床意义。

Inhibition of PMA-induced endothelial cell activation and adhesion by over-expression of domain negative IκBα protein

AIM: NF-κB, regulate the expression of cytokine-inducible genes involving immune and inflammatory responses, will be potential therapy approach for allograft from rejection. In this study, we use pCMV-IκBαM vector to inhibit NF-κB activation and investigate the effect of pCMV-IκBαM in inhibition of T cells adhesion to endothelial cells. METHODS: The NF-κB activity was detected with pNF-κB reporter gene and electrophoretic mobility shift assay. Expression of cell surface molecules was detected by RT-PCR and flow cytometer. The cell-cell adhesion assay was performed to determine the effect of pCMV-IκBαM in inhibition of T cells adhesion to endothelial cells. RESULTS: We could find that NF-κB activity is inhibited by over-expression of non-degraded IκBα protein. Expression of adhesion molecules like ICAM-1, VCAM-1, and P-selectin as well as cell-cell adhesion were inhibited significantly by transfection of the pCMV-IκBαM vector. CONCLUSION: Our results indicate that the pCMVIκBαM, which inhibit the activity of NF-κB through over-expression of non-degraded IκBα protein, can be used for gene therapy in diseases involving NF-κB activation abnormally like organ transplantation via inhibiting cell adhesion.

Selective proliferation of human γδ T cells in vitro

The effect of monoethylphosphate (MEP, commercial available or synthesized) together with IL-2 on the selective proliferation of human γ~δ T cells in Vitro from peripheral blood mononuclear cells (PBMC) of healthy donors and of cancer patients was investigated. The γ~δ T cells were stimulated by MEP to proliferate in a dose-dependent manner. The effect of synthesized MEP was 10 times greater than that of commercial MEP. When the PBMCs of healthy donors were cultured for 25 d in the medium containing different concentrations of MEP, the total cell number increased about 1000-3000 fold; and the ratio of γ~δ T cells reached to 70-80%. The selective expansion of γ~δ T cells depended on the synergic action of MEP and IL-2. The bulk cultured γ~δ T cells exhibited obvious cytotoxic activities against allogenic tumor cell lines (SQ-5,K562 alld Daudi) and autologous tumor cells. The culture system described here not only offers a simple method for obtaining a large number of γ~δ T cells which may become a new effector in the adoptive immunotherapy, but also provides a useful model for the further studies of the structure and function of γ~δ T cells in vitro.

The roles of toll-like receptors in carcinogenesis and cancer immunotherapy

Toll-like receptors （TLRs） are probably the most important class of pattern-recognition receptors. Members of the TLR family play key roles in the both innate and adaptive immune responses. Recognition of pathogen-associated molecular patterns （PAMPs） by TLRs, either alone or in heterodimedzation with other TLR or non-TLR receptors, induces the production of signals that are responsible for the activation of genes important for an effective host defense, especially those of proinflammatory cytokines. Thus, TLRs are involved in the development of many pathological conditions including infectious diseases, tissue damage, and cancer especially. In this review, the contribution of TLRs to tumorgenesis is evaluated. We hope to provide new insight into the progression of cancer and more importantly into the potential for TLRs as targets of therapeutics.

Trichosanthin functions as Th2-type adjuvant in induction of allergic airway inflammation

It is important to understand the pathogenesis of asthma induced by natural allergens, which could exclude the interference of artificial adjuvant and provide insights of natural immune response in the disease. In the present study, we show that Trichosanthin （TCS） could induce airway inflammation even without the help of alum. Furthermore, TCS appeared capable of replacing alum to promote OVA-specific airway inflammation. TCS induced accumulation of IL-4-producing eosinophils in peritoneum at an early stage and the adjuvant function of TCS was eliminated by blockage of IL-4 at this stage. Finally, the eosinophils triggered by TCS from WT mice, but not from IL-4- deficient mice were shown to function as adjuvant for the induction of OVA-specific Th2 responses. Our data indicate that TCS is not only an allergen, but also a Th2-typc adjuvant modulating the switching of immune responses to a Th2 pathway. This chain of events results from IL-4 production by eosinophils at an early stage of TCS-priming. In conclusion, TCS may be useful as a Th2 adjuvant, and innate immune cells, such as eosinophils, may be a good target to study the initiation of Th2 response.

Hepato-biliary profile of potential candidate liver progenitor cells from healthy rat liver

AIM： To evaluate the presence of progenitor cells in healthy adult rat liver displaying the equivalent ad- vanced hepatogenic profile as that obtained in humans. METHODS： Rat fibroblastic-like liver derived cells （rFLDC） were obtained from collagenase-isolated liver cell suspensions and characterized and their phenotype profile determined using flow cytometry, immunocyto- chemistry, reverse transcription polymerase chain reac- tion and functional assays. RESULTS： rFLDC exhibit fibroblastoid morphology, ex- press mesenchymal （CD73, CD90, vimentin, m-smooth muscle actin）, hepatocyte （UGTIA1, CK8） and biliary （CK19） markers. Moreover, these cells are able to store glycogen, and have glucose 6 phosphatase activity, but not UGTIA1 activity. Under the hepatogenic differentia- tion protocol, rFLDC display an up-regulation of hepatocyte markers expression （albumin, tryptophan 2,3-di- oxygenase, G6Pase） correlated to a down-regulation of the expression of the biliary marker CK19. CONCLUSION： Advanced hepatic features observed in human liver progenitor cells could not be demonstrated in rFLDC. However, we demonstrated the presence of an original rodent hepato-biliary cell type.

Evaluation of the Pathogenicity and Immune Response of Nervous Necrosis Virus Isolated in Vietnam

Eight strains of nervous necrosis virus （NNV） isolated in Vietnam were used to detect the pathogenicity and immune response in sea bass （SB）. All strains induced cytopathic effect in SB cell line, complete destruction of monolayer of cells appeared after seven days post infection （dpi）. Virus titer was different for each strain, TCIDso ranged from 102.7 to 1069, and LDs0 from 1015 to 1075. Five NNV strains named QN 02, QN 05, QN 07, ND 11 and KH 05 had higher virulence than the other three, the first causing 100% mortality in experimental fish 3-5 dpi. NNV KH 05 had the highest antigenic similarity, and it was inactivated completely by 0.2% formalin, 0.002 mol/L binary ethylenimine （BEI） and 0.1% beta-propiolactone. The neutralization antibody titer obtained in fish of groups immunized by BEI 0.002 M and beta-propiolactone 0.1% inactivated virus was four to eight times higher than that of the group treated with the formalin inactivated virus. The antibody titer in fish immunized with beta-propiolactone inactivated virus was more persistent. The efficacy of vaccines developed from beta-propiolactone inactivated virus and aluminium hydroxide （AH） or aluminum phosphate （AP） was observed by intramuscularly immunizing Epinephelusfuscoguttatus size 1.5 cm. Neutralizing antibodies appeared in vaccinated fish on 10th day post-immunization （dpi） at a dilution of 1：16; 1：32 and highest levels were reached on 30-45 dpi, at dilutions of 1：256 and 1：512, after treatment with AH and AP vaccine, respectively. The relative percent of survival （RPS） of vaccine at 30 dpi was highest with challenge doses 0.2-1 × 10^6.8 TCIDs0, the RPS varied from 80%-83.3% in both groups of AH and AP immunization. This result provides the basis for developing a vaccine against NNA disease.

Effect of Plasmodium yoelii YM Infection on Vaccination with 19 kDa Carboxylterminus of the Merozoite Surface Protein 1 (MSP1_(19))

We have previously demonstrated the ability of malaria parasites to interfere with specific immune responses. CD4 T cells specific to parasite antigens, but not CD4 T cells specific to an irrelevant antigen, ovalbumin (OVA), are de- leted via apoptosis during malaria infection. It is of interest, therefore, to investigate the immune responses that developed following vaccination with the 19 kDa carboxylterminus of the merozoite surface protein 1 (MSP119) in mice that had previ- ously experienced malaria infection. In this study, pre-exposure of mice to Plasmodium yoelii elicited native anti-MSP119 an- tibody responses, which could be boosted by vaccination with recombinant MSP119 . likewise, infection of MSP119-primed mice with Plasmodium yoelii ( P . yoelii) led to an increase of anti-MSP119 antibodies. MSP119 vaccination of malaria pre- exposed mice or immunization by infection/cure of MSP119-primed mice enabled the mice to survive challenge infection, with the former group having slightly lower parasitaemia. The data suggest that exposure to malaria infection primes a natural im- mune response which can be boosted by vaccination. This information is relevant to the development of a vaccine for use in individuals living in malaria-endemic areas.

Mechanism of Immune Hyporesponsiveness Induced by Recipientderived Immature Dendritic Cells in Rat Liver Transplantation

Objective： The use of donor-derived immature dendritic cells （imDC） has become a promising approach to induce immune tolerance or immune hyporesponsiveness. However, donor-derived imDC needs to be harvested for a few days and transfused into the recipient in 5-10 days before transplantation, which is practically impossible in a clinical setting where donor organs are mainly harvested from cadavers. Moreover, donor-derived imDC might be cleared by allogeneic reaction offsetting induced immune tolerance or immune hyporesponsiveness. In our study, we further explored the underlying mechanism of immune hyporesponsiveness induced by donor-antigen-unloaded recipient-derived imDC by transfusing these imDC into rats in 1 day before liver transplantation. This paper is to study the mechanism of immune hyporesponsiveness induced by donor-antigen-unloaded recipient-derived imDC and its protection of liver grafts in rats. Methods： 40 SD rats （donor） and 40 male Wistar rats （recipient） were randomly divided into 4 groups： control, cyclosporine A （CsA）, mature DC （mDC）, and imDC; with 10 SD rats and 10 Wistar rats for each group. Animal models of acute graft rejection were established with these rats. Corresponding treatments were given before or after transplantation. In the control group, Wistar rats received no treatment other than liver transplantation. In the CsA group, Wistar rats underwent liver transplantation plus CsA treatment （10 mg/kg·d） in the starting day 2 after transplantation. For the mDC group, recipient-derived mDC （1 × 10^6/rat） were infused intravenously via the dorsal vein of the penis to recipient rats. For the imDC group, imDC （1× 10^6/rat） were injected into recipient rats via the dorsal vein of the penis. In each group, 5 recipients were executed at 10 days after transplantation; the remaining five recipients were kept for the observation of survival time. Blood samples were collected for the measurement of ALT and TBIL; IL-2, IFN-γ, IL-4 and IL-10 and levels were measured with double-antibody sandwich ELISA. Liver tissue was harvested for HE staining and the observation of histological features. Acute rejection was evaluated with Banff classification. Expression levels of Fas-L/Fas in the grafts were detected by iminunohistochemieal staining; and western blot was used to detect the expression level of Scurfin. Results： The median survival times （MST） of the liver allografls in the CsA and imDC group were significantly longer than those in the control or mDC group （P〈0.05）. The serum levels of ALT and TBIL in the control and mDC groups were significantly higher than those of the CsA or imDC group （P〈0.05）. Compared with the CsA anti imDC group, the levels of IL-2 and IFN-γ were higher but the levels of IL-4 and IL-10 were lower than those of the control and mDC groups （P〈0.01）. Slight or no rejection reaction was found in the CsA anti imDC groups （P〈0.05）. The expression level of Scurfin protein in CD4^＋ CD25^＋ T cells of the imDC group was significantly higher than that of three other groups （P〈 0.05）. Conclusion： Donor-antigen-unloaded recipient- derived imDC is an effective treatment in inducing immune hyporesponsiveness by blocking indirect recognition in rat liver transplantation model. Survival span was significantly prolonged by its protective effect. The mechanism of immune hyporesponsiveness induced hy imDC transfusion may involve the preprocesses of T cell apoptosis induction, immune tolerance or hyporesponsiveness in T cells, induction of the shift in TH1/TH2 balance, selection activation of Th2 subset, or induction of regulatory T cell.

Influence of systemic immune and cytokine responses during the acute phase of zoster on the development of postherpetic neuralgia

Postherpetic neuralgia(PHN) is a severe sequela of herpes zoster(HZ).Until now,only age and pain severity were considered predisposing factors for the development of PHN.We evaluated 49 patients with acute phase HZ,10 of whom developed PHN(Group A) and 39 of whom did not develop PHN(Group B).Twenty-five healthy volunteers similar in age and gender distribution to the study group were recruited as controls(Group C).Numbers of serum CD3+(pan-T lymphocytes),CD4+(helper/inducer),and CD8+(suppressor/cytotoxic) lymphocytes were decreased significantly in Groups A and B relative to the control group,but there were no statistical differences between Groups A and B.Interleukin(IL)-1β,IL-6,tumor necrosis factor(TNF)-α,IL-8,and IL-10 were significantly elevated in Groups A and B relative to Group C.IL-6 was significantly higher in Group A than in Group B,and was significantly positively correlated with pain severity scored on a visual analog scale.Therefore,we suggest that the inflammatory response,especially that of IL-6,in the acute phase of HZ may be associated with hyperalgesia and the development of PHN.

肝内乙肝病毒cccDNA的研究进展

肝内HBVcccDNA被认为在乙肝病毒持续感染中是停药反跳和病毒耐药的关键因素.本文就肝内HBVcccDNA的产生、属性、检测方法、清除机制,及与现有抗病毒治疗的关系,作了综述.期望为终结乙肝病毒持续感染提供一些理论基础.