Nucleotide oligomerization domain 2 contributes to the innate immune response in THCE cells stimulated by Aspergillus fumigatus conidia

AIM: To investigate the expression of nucleotide oligomerization domain 2 (NOD2) in the immortalized human corneal epithelial cell line (THCE), and its role in the innate immune response triggered by inactive Aspergillus fumigatus (Af) conidia. METHODS: The normal THCE cells were investigated as controls. After incubation with inactive Af conidia for 0.5, 2, 4, 6, and 8 hours, THCE cells were harvested, mRNA expression of NOD2 and receptor interacting protein 2 (RIP2) was detected by RT-PCR. Intracellular proteins including NOD2, NF-kappa B and proinflammatory cytokines such as TNF-alpha, IL-8, IL-6 in the cell supernatant were analyzed by ELISA. RESULTS: Our data indicate that NOD2 expressed in the normal THCE cells. After triggered by the inactive Af conidia, the expression of NOD2, RIP2 mRNA and the secretion of NOD2, NF-kappa B, TNF-alpha, IL-8, IL-6 both increased in a time-depended manner, and reached the peak point at 4, 6, 6, 4, 6, 6, 4 hours, respectively. And after pretreated with NOD2 neutralizing antibody, the expression of RIP2, NF-kappa B, TNF-alpha, IL-8 both decreased dramatically at the peak point, while the secretion of IL-6 changed little. CONCLUSION: The results of this study suggest that NOD2 exists and expresses in the THCE cells, and contributes to the innate immune responses triggered by inactive Afconidia by induction of proinflammatory cytokines such as TNF-alpha and IL-8 through the NF-kappa B pathway.

Correlation of serum nutrient levels with immune cell differentiation and inflammatory response activation in children with pneumonia

Objective:To investigate the correlation of serum nutrient levels with immune cell differentiation and inflammatory response activation in children with pneumonia.Methods:200 children with pneumonia who were treated in our hospital between April 2015 and August 2017 were selected as the pneumonia group, and 100 healthy children who were vaccinated in this hospital during the same period were selected as the normal control group. The differences in serum levels of nutrients, Th1/Th2 cytokines, Th17/Treg cytokines and inflammatory mediators were compared between the two groups. Pearson test was used to assess the relationship between serum nutrient levels and disease severity.Results: Serum Vit A, Fe and Zn levels of pneumonia group were lower than those of control group. The differences in serum Vit D, Ca and Mg levels were not statistically significant between the two groups of children. Serum Th1 cytokines IL-2 and TNF-β contents of pneumonia group were lower than those of control group whereas Th2 cytokines IL-4 and IL-5 contents were higher than those of control group;Th17 cytokines IL-17, IL-21 and IL-22 contents were higher than those of control group whereas Treg cytokines IL-10 and TGF-β contents were lower than those of control group;inflammatory mediators CRP, PCT and MCP-1 contents were significantly higher than those of control group. Pearson test showed that serum nutrients Vit A, Fe and Zn levels in children with pneumonia were directly correlated with the degree of immune cell differentiation and inflammatory response.Conclusion: Serum Vit A, Fe, Zn and other nutrient levels abnormally decrease in children with pneumonia, and the specific level are directly correlated with the severity of the disease.

Mesenchymal stromal cells as potential immunomodulatory players in severe acute respiratory distress syndrome induced by SARSCoV- 2 infection

Severe acute respiratory syndrome coronavirus-2 and the related coronavirus disease-19(COVID-19)is a worldwide emerging situation,which was initially reported in December 2019 in Wuhan,China.Currently,more than 7258842 new cases,and more than 411879 deaths have been reported globally.This new highly transmitted coronavirus is responsible for the development of severe acute respiratory distress syndrome.Due to this disorder,a great number of patients are hospitalized in the intensive care unit followed by connection to extracorporeal membrane oxygenation for breath supporting and survival.Severe acute respiratory distress syndrome is mostly accompanied by the secretion of proinflammatory cytokines,including interleukin(IL)-2,IL-6,IL-7,granulocyte colony-stimulating factor(GSCF),interferon-inducible protein 10(IP10),monocyte chemotactic protein-1(MCP1),macrophage inflammatory protein 1A(MIP1A),and tumor necrosis factor alpha(TNF-α),an event which is known as“cytokine storm”.Further disease pathology involves a generalized modulation of immune responses,leading to fatal multiorgan failure.Currently,no specific treatment or vaccination against severe acute respiratory syndrome coronavirus-2(SARS-CoV-2)has been developed.Mesenchymal stromal cells(MSCs),which are known for their immunosuppressive actions,could be applied as an alternative co-therapy in critically-ill COVID-19 patients.Specifically,MSCs can regulate the immune responses through the conversion of Th1 to Th2,activation of M2 macrophages,and modulation of dendritic cells maturation.These key immunoregulatory properties of MSCs may be exerted either by produced soluble factors or by cell-cell contact interactions.To date,several clinical trials have been registered to assess the safety,efficacy,and therapeutic potential of MSCs in COVID-19.Moreover,MSC treatment may be effective for the reversion of ground-glass opacity of damaged lungs and reduce the tissue fibrosis.Taking into account the multifunctional properties of MSCs,the proposed stem-cell-based therapy may be proven significantly effective in critically-ill COVID-19 patients.The current therapeutic strategy may improve the patient’s overall condition and in parallel may decrease the mortality rate of the current disease.

Relationship between Th17 immune response and cancer

Cancer is the second leading cause of death worldwide and epidemiological projections predict growing cancer mortality rates in the next decades.Cancer has a close relationship with the immune system and,although Th17 cells are known to play roles in the immune response against microorganisms and in autoimmunity,studies have emphasized their roles in cancer pathogenesis.The Th17 immune response profile is involved in several types of cancer including urogenital,respiratory,gastrointestinal,and skin cancers.This type of immune response exerts pro and antitumor functions through several mechanisms,depending on the context of each tumor,including the protumor angiogenesis and exhaustion of T cells and the antitumor recruitment of T cells and neutrophils to the tumor microenvironment.Among other factors,the paradoxical behavior of Th17 cells in this setting has been attributed to its plasticity potential,which makes possible their conversion into other types of T cells such as Th17/Treg and Th17/Th1 cells.Interleukin(IL)-17 stands out among Th17-related cytokines since it modulates pathways and interacts with other cell profiles in the tumor microenvironment,which allow Th17 cells to prevail in tumors.Moreover,the IL-17 is able to mediate pro and antitumor processes that influence the development and progression of various cancers,being associated with variable clinical outcomes.The understanding of the relationship between the Th17 immune response and cancer as well as the singularities of carcinogenic processes in each type of tumor is crucial for the identification of new therapeutic targets.

基于Th1/Th2表达探究特异性免疫对哮喘小鼠肺泡灌洗液炎性反应的影响

目的 基于Th1/Th2表达探究特异性免疫对哮喘小鼠肺泡灌洗液炎性反应的影响。方法 选择40只小鼠分为对照组、模型组、SIT组及地塞米松组,每组10只。除了对照组外均建立哮喘小鼠模型,激发阶段后SIT组注射1 mg的OVA,地塞米松组灌胃0.075 mg/mL溶液,其余大鼠注射等体积的PBS溶液。采用肺功能仪检测气道反应;经瑞氏-吉姆萨染色观察肺泡灌洗液(BALF)炎性细胞;酶联免疫吸附法(ELISA)检测BALF中细胞因子IL-13、IL-4、IL-5及INF-γ;HE染色观察肺组织形态;PAS染色观察肺气道上皮杯状细胞活性;流式细胞术检测肺组织中Th1及Th2占比。结果 特异性免疫可显著降低模型小鼠气道高反应性、减少BALF内炎性细胞活性,并可通过升高Th1降低Th2而抑制哮喘发生发展。结论 特异性免疫可缓解哮喘小鼠气道高反应性,抑制炎性反应,并通过改善气道上皮杯状细胞增生而缓解通气,可能与调节Th1/Th2表达相关。

Orchestration between ILC2s and Th2 cells in shaping type 2 immune responses

The type 2 immune response is critical for host defense against large parasites such as helminths.On the other hand,dysregulation of the type 2 immune response may cause immunopathological conditions,including asthma,atopic dermatitis,rhinitis,and anaphylaxis.Thus,a balanced type 2 immune response must be achieved to mount effective protection against invading pathogens while avoiding immunopathology.The classical model of type 2 immunity mainly involves the differentiation of type 2 T helper(Th2)cells and the production of distinct type 2 cytokines,including interleukin-4(IL-4),IL-5,and IL-13.Group 2 innate lymphoid cells(ILC2s)were recently recognized as another important source of type 2 cytokines.Although eosinophils,mast cells,and basophils can also express type 2 cytokines and participate in type 2 immune responses to various degrees,the production of type 2 cytokines by the lymphoid lineages,Th2 cells,and ILC2s in particular is the central event during the type 2 immune response.In this review,we discuss recent advances in our understanding of how ILC2s and Th2 cells orchestrate type 2 immune responses through direct and indirect interactions.

CD4+ T cell responses in hepatitis C virus infection

Hepatitis C virus (HCV) infection is a major cause of liver damage, with virus-induced end-stage disease such as liver cirrhosis and hepatocellular carcinoma resulting in a high rate of morbidity and mortality worldwide. Evidence that CD4+ T cell responses to HCV play an important role in the outcome of acute infection has been shown in several studies. However, the mechanisms behind viral persistence and the failure of CD4+ T cell responses to contain virus are poorly understood. During chronic HCV infection, HCV-specific CD4+ T cell responses are rela- tively weak or absent whereas in resolved infection these responses are vigorous and multispecific. Persons with a T-helper type I profile, which promotes cellular effec- tor mechanisms are thought to be more likely to experi- ence viral clearance, but the overall role of these cells in the immunopathogenesis of chronic liver disease is not known. To define this, much more data is required on the function and specificity of virus-specific CD4+ T cells, especially in the early phases of acute disease and in the liver during chronic infection. The role and possible mechanisms of action of CD4+ T cell responses in deter- mining the outcome of acute and chronic HCV infection will be discussed in this review.

成人接种2剂新冠灭活疫苗12个月后T细胞免疫应答特点

目的评估成年人接种新型冠状病毒(SARS-CoV-2)灭活疫苗12个月后不同抗原特异性T细胞免疫应答的特点。方法解放军总医院第五医学中心2022年4-6月招募15名健康成年人,于接种2剂新冠灭活疫苗12个月后采集其静脉血标本,以基于多色流式细胞术的活化诱导标记法(AIM)检测SARS-CoV-2抗原特异性T淋巴细胞水平,并分析其记忆表型与亚群分化特点。结果成年人接种2剂灭活疫苗12个月后,90%以上个体可检测到Spike及Non-spike特异性CD4^(+)T细胞反应(S:14/15,P=0.0001;NS:15/15,P<0.0001);80%个体检测到Spike及Non-spike特异性CD8^(+)T细胞反应(S:12/15,P=0.0463;NS:12/15,P=0.0806)。抗原特异性CD4^(+)T细胞主要表现为中央记忆细胞(CM)、1型效应记忆细胞(EM1)记忆表型,以及1/17型辅助性T细胞(Th1/17)、2型辅助性T细胞(Th2)辅助表型。结论灭活疫苗接种后能诱导广泛且持久的抗原特异性CD4^(+)T细胞反应,可能是当前国内新型冠状病毒感染重症化比例较低的关键因素。

Mycobacterium tuberculosis Mce2E suppresses the macrophage innate immune response and promotes epithelial cell proliferation

The intracellular pathogen Mycobacterium tuberculosis(Mtb)can survive in the host and cause disease by interfering with a variety of cellular functions.The mammalian cell entry 2(mce2)operon of Mtb has been shown to contribute to tuberculosis pathogenicity.However,little is known about the regulatory roles of Mtb Mce2 family proteins towards host cellular functions.Here we show that the Mce2 family protein Mce2E suppressed the macrophage innate immune response and promoted epithelial cell proliferation.Mce2E inhibited activation of the extracellular signal-regulated kinase(ERK)and Jun N-terminal kinase(JNK)mitogen-activated protein kinase(MAPK)signaling pathways in a non-canonical D motif(a MAPK-docking motif)-dependent manner,leading to reduced expression of TNF and IL-6 in macrophages.Furthermore,Mce2E promoted proliferation of human lung epithelium-derived lung adenoma A549 cells by inhibiting K48-linked polyubiquitination of eEF1A1 in aβstrand region-dependent manner.In summary,Mce2E is a novel multifunctional Mtb virulence factor that regulates host cellular functions in a niche-dependent manner.Our data suggest a potential novel target for TB therapy.

Long-term asymptomatic SARS-CoV-2 infection associated with deficiency on multiple immune cells

The immune responses and the function of immune cells among asymptomatic severe acute respiratory syndrome coronavirus 2(SARS‐CoV‐2)infection cases,especially in immuno‐compromised individuals,remain largely unknown.Here we present a case of asymptomatic SARS‐CoV‐2 infection that lasted for at least 67 days.The patient has administrated Thymalfasin as 1.6 mg per dose every other day from Day 45 to 70,plus 200 mg per dose Arbidol antiviral therapy three doses per day from Day 48 to 57.Throughout the infection,no anti‐SARS‐CoV‐2 specific IgM or IgG antibodies were detected.Instead,the patient showed either a low percentage or an absolute number of non‐classical monocytes,dendritic cells(DCs),CD4^(+)T cells,and regulatory T cells(Tregs),which may account for the clinical feature and absence of antibody response.This case may shed new light on the outbreak management related to control/prevention,treatment,and vaccination of SARS‐CoV‐2 and other virus infections in immunocompromised individuals.

左旋精氨酸通过活化树突状细胞增强约氏疟原虫感染DBA/2小鼠的Th1应答效应

目的探讨左旋精氨酸(L-Arginine,L-Arg)对致死型约氏疟原虫(Plasmodium yoelii 17XL,P.y17XL)感染DBA/2小鼠Th1免疫应答的调节效应。方法 DBA/2小鼠随机分为两组,对照组和L-Arg组,每组20只,分别给予DBA/2小鼠生理盐水和L-Arg(1.5g/kg)连续灌胃预处理7d后,每鼠经腹腔感染1×10~6个P.y17XL寄生的红细胞(pRBC)。统计两组小鼠红细胞感染率和小鼠存活率。感染后第0、3和5天每组分别处死4只小鼠,取脾组织制备脾细胞悬液,流式细胞术检测CD4^+CD69^+T细胞、F4/80^+CD36^+巨噬细胞、髓样树突状细胞mDCs(CD11c^+CD11b^+)、浆样树突状细胞pDCs(CD11c^+B220^+)数量,ELISA法检测脾细胞培养上清中γ干扰素(IFN-γ)的分泌水平,Griess反应检测脾细胞培养上清中一氧化氮(NO)含量。结果与对照组(45%)比较,L-Arg组小鼠的最高红细胞感染率降到20%,自愈时间从22d缩短到20d。感染后第3天,L-Arg组小鼠CD4^+CD69^+T细胞数量[(11.27±0.97)%]、IFN-γ分泌水平[(767.86±20.56)pg/ml]、F4/80^+CD36^+巨噬细胞数量[(36.46±1.33)%]、NO产生水平[(78.66±2.89)μmol/L]、mDCs和pDCs数量[(10.02±0.37)%和(9.01±0.53)%]均显著高于对照组[分别为(7.3±0.68)%、(485.84±39.31)pg/ml、(29.61±0.47)%、(42.51±1.32)μmol/L]、(5.51±0.87)%和(5.60±0.85)%](P<0.05),而感染后第5天均无明显差异。结论 L-Arg预处理可促进DCs的活化,从而促进DBA/2小鼠于感染早期Th1免疫应答进一步有效建立。

新疆野生荒漠肉苁蓉醇提物调节小鼠DCs成熟对Th_(1)/Th_(2)的免疫增强作用

旨在探讨新疆野生荒漠肉苁蓉醇提物(ethanol extracts of wild Cistanche deserticola,EEWCD)调节Th1/Th2免疫反应的特点及初步的作用机制。采用卵清白蛋白(ovalbumin,OVA)为抗原,研究EEWCD对小鼠体液免疫,细胞免疫,细胞因子分泌,树突状细胞(dendritic cells,DCs)的成熟和调节性T细胞(regulatory T cell,Treg)等的影响。EEWCD低、中、高剂量(分别记作L、M、H)分别与OVA混合,ICR小鼠随机分为0.9%NaCl、EEWCD、OVA、OVA-EEWCD-L、OVA-EEWCD-M、OVA-EEWCD-H和OVA-铝佐剂免疫组。皮下免疫2次,间隔2周。小鼠免疫后,ELISA法检测抗体滴度及分型,MTT检测脾细胞增殖水平,FACS检测CD4^(+)IL-4、CD4^(+)IFN-γ和CD8^(+)IFN-γ的水平,以及DCs表面分子与Treg表达水平。结果显示,EEWCD提高了OVA特异性IgG抗体2~3倍;在初次免疫后21 d显著促进IgG_(1)和IgG_(2a)的表达水平(P<0.05);显著促进OVA特异性脾细胞增殖以及T/B细胞的活化(P<0.05);显著促进CD4^(+)IL-4、CD4^(+)IFN-γ和CD8^(+)IFN-γ的分泌(P<0.05)。同时,EEWCD也显著促进了DCs的CD40、CD80、CD86和MHCII的表达(P<0.05),下调了Treg的水平(P<0.05)。EEWCD-M为最佳剂量。监测免疫后小鼠行为及体重,小鼠行为没有异常,且同一时间点各组体重之间差异不显著(P>0.05)。综上表明,EEWCD能够促进OVA特异性的Th_(1)/Th_(2)免疫反应,尤其促进Th_(1)型反应,具有良好的免疫调节活性,其作用机制可能为通过激活DCs的成熟,促进IL-4和IFN-γ的分泌,降低Treg的水平调节Th_(1)/Th_(2)免疫反应的动态平衡。

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。

Ma Huang Tang ameliorates asthma though modulation of Th1/Th2 cytokines and inhibition of Th17 cells in ovalbumin-sensitized mice

AIM： Ma Huang Tang （Ephedra decoction, MHT） is a famous classical formula from Shang Han Lun by Zhang Zhongjing in the Han Dynasty. The anti-asthmatic effects of MHT and the possible mechanisms were tested. METHOD： An asthma model was established by ovalbumin （OVA）-induction in mice. A total of forty-eight mice were randomly assigned to six experimental groups： control, model, dexamethasone （2 mg·kg^-1） and MHT （5, 10, and 20 mg·kg^-1）. Airway resistance （Raw） was measured by the forced oscillation technique, histological studies were evaluated by hematoxylin and eosin （HE） staining, Thl/Th2 and Th17 cytokines were evaluated by enzyme-linked immunosorbent assay （ELISA）, and Thl7 cells were evaluated by flow cytometry （FCM）.RESULTS： This study demonstrated that MHT inhibited OVA-induced increases in Raw and eosinophil cotmt; interleukin （IL）-4 and IL-17 levels were recovered in bronchoalveolar lavage fluid, increased IFN-γ level in bronchoalveolar lavage fluid. Histological studies demonstrated that MHT substantially inhibited OVA-induced eosinophilia in lung tissue. Flow cytometry studies demonstrated that MHT substantially inhibited Thl 7 cells.CONCLUSION： These findings suggest that MHT may effectively ameliorate the progression of asthma, and could be further investigated for potential use as a therapy for patients with allergic asthma,

Duchesnea Phenolic Fraction Inhibits Tumor Growth through Restoring the Th1/Th2 Balance in U14 Cervical Cancer Bearing Mice

Duchesnea indica (Andr.) Focke has been traditionally used to treat cancer in Asian countries for centuries. In the present study, transplanted U14 cervical cancer mouse model was used to evaluate the antitumor and immunomodulatory activity of Duchesnea phenolic fraction (DPF). ELISA and RIA assay were employed to measured the serum concentration of Th1/Th2 cytokines (IL-2, IL-4, IFN-γ and TNF-α). Administration with 0.25 g/kg, 0.5 g/kg and 1 g/kg DPF significantly reduced the tumor weight by 34.37%, 43.89% and 56.28%, respectively, as compared to the tumor control group. Furthermore, the serum level of IL-2, IFN-γ and TNF-α increased and IL-4 level decreased in a dose-dependent manner during DPF treatment, indicating that the antitumor activity of DPF may be associated with the decrease of TNF-α level and restoration of the balance of Th1/Th2 cell responses. These data suggested that DPF, a mixture of plant polyphenols, had potent anticancer activity which was in part accomplished by its immunomodulatory ability.

Mild Cytokine Elevation, Moderate CD4^+ T Cell Response and Abundant Antibody Production in Children with COVID-19

Children with Coronavirus Disease 2019(COVID-19) were reported to show milder symptoms and better prognosis than their adult counterparts, but the difference of immune response against SARS-CoV-2 between children and adults hasn’t been reported. Therefore we initiated this study to figure out the features of immune response in children with COVID-19.Sera and whole blood cells from 19 children with COVID-19 during different phases after disease onset were collected.The cytokine concentrations, SARS-CoV-2 S-RBD or N-specific antibodies and T cell immune responses were detected respectively. In children with COVID-19, only 3 of 12 cytokines were increased in acute sera, including interferon(IFN)-cinduced protein 10(IP10), interleukin(IL)-10 and IL-16. We observed an increase in T helper(Th)-2 cells and a suppression in regulatory T cells(Treg) in patients during acute phase, but no significant response was found in the IFN-cproducing or tumor necrosis factor(TNF)-a-producing CD8?T cells in patients. S-RBD and N IgM showed an early induction, while S-RBD and N IgG were prominently induced later in convalescent phase. Potent S-RBD IgA response was observed but N IgA seemed to be inconspicuous. Children with COVID-19 displayed an immunophenotype that is less inflammatory than adults, including unremarkable cytokine elevation, moderate CD4?T cell response and inactive CD8?T cell response, but their humoral immunity against SARS-CoV-2 were as strong as adults. Our finding presented immunological characteristics of children with COVID-19 and might give some clues as to why children develop less severe disease than adults.

Immune responses to SARS-CoV-2 infection in Humans and ACE2 humanized mice

The coronavirus disease 2019(COVID-19)pandemic caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)represents a major public health threat worldwide.Insight into protective and pathogenic aspects of SARS-CoV-2 immune responses is critical to work out effective therapeutics and develop vaccines for controlling the disease.Here,we review the present literature describing the innate and adaptive immune responses including innate immune cells,cytokine responses,antibody responses and T cell responses against SARS-CoV-2 in human infection,as well as in AEC2-humanized mouse infection.We also summarize the now known and unknown about the role of the SARS-CoV-2 immune responses.By better understanding the mechanisms that drive the immune responses,we can tailor treatment strategies at specific disease stages and improve our response to this worldwide public health threat.

高敏C-反应蛋白在酮症或酮症酸中毒起病的2型糖尿病患者的检测意义

目的了解自发酮症或酮症酸中毒起病的2型糖尿病患者的免疫炎性反应和胰岛β细胞损害程度。方法检测以自发酮症或酮症酸中毒起病的2型糖尿病患者血清高敏C-反应蛋白(hs-CRP)、抗谷氨酸脱羧酶(GAD)抗体的水平,及空腹胰岛素、C-肽及餐后2h胰岛素、C-肽水平。用酶联免疫吸附试验(ELISA)法测定hs-CRP的水平,胰岛素(Ins)、C-肽、GAD抗体用化学发光法检测。结果①自发酮症或酮症酸中毒起病的2型糖尿病患者患者血清hs-CRP与对照组(32382.11±1685.68ng/ml比10775.25±1615.77ng/ml)相比明显增高,差异有统计学意义(P<0.05)。②以酮症酸中毒起病的2型糖尿病患者外周血GAD抗体阳性率(14.0%),与对照组(13.3%)比较,差异无统计学意义(P>0.05)。③自发酮症或酮症酸中毒起病的2型糖尿病患者外周血空腹胰岛素、C-肽、餐后2h胰岛素、餐后2hC-肽水平明显低于对照组差异有统计学意义(P<0.05)。结论机体免疫炎症反应是促使2型糖尿病患者自发酮症或酮症酸中毒的重要机制,是导致2型糖尿病患者急性胰岛β细胞损伤的主要原因。

人抗SARS-CoV-2感染适应性免疫应答的研究进展

由SARS-CoV-2感染引起的COVID-19为全球流行病,严重威胁全球公共卫生,感染无特异性免疫力人群影响人们改变社交行为和习惯,产生全球经济负担,目前尚无有效治疗药物。因此,自然感染诱导的适应性免疫应答备受关注。自然感染SARS-CoV-2可诱导绝大多数成人产生体液免疫应答和细胞免疫应答,形成高滴度S蛋白特异性IgM、IgG和IgA类抗体、高水平中和抗体、强CD4+T细胞应答、特异性记忆B细胞和记忆T细胞,可获得抗SARS-CoV-2感染的免疫保护,但免疫保护持续时间仍不确定。对SARS-CoV-2感染诊断、血清学监测、免疫策略、感染防控及疫苗开发等有重要意义。

HCV-NS3重组腺病毒转染树突状细胞体内诱导抗原特异性Th1应答的研究

目的:探讨表达丙型肝炎病毒(HCV)非结构蛋白(NS3)基因的重组腺病毒转染树突状细胞体内诱导特异性Th1细胞免疫应答。方法:分离培养小鼠骨髓树突状细胞,制备表达HCV-NS3蛋白的重组腺病毒转染树突状细胞(DC-AdNS3)疫苗,采用流式细胞术和免疫印迹法分析鉴定细胞及抗原蛋白表达。采用腹腔注射途径免疫接种BALB/c小鼠两次,每次间隔10天,3×105细胞/次。末次接种10天后,采用ELISPOT法和ELISA法分别测定脾NS3特异性分泌IFN-γ的T细胞反应以及细胞因子水平。结果:重组腺病毒转染DC可刺激DC成熟,同时可在DC内成功表达NS3蛋白。小鼠两次接种DC-AdNS3产生明显升高的分泌IFN-γ的T细胞反应(P<0·01),脾T细胞悬液内可测得高水平的IL-2和IFN-γ(P<0·01)以及显著降低的IL-10(P<0·05)。结论:DC-AdNS3疫苗可在BALB/c小鼠体内激发产生抗原特异性的Th1细胞免疫应答,为抗HCV感染的疫苗研究提供参考依据。