肺结核并重症肺炎患者细胞免疫功能研究

目的 了解肺结核合并重症肺炎患者的细胞免疫功能状态.方法 选取我院56例肺结核合并重症肺炎患者和40例健康对照者,对两组外周血进行T细胞亚群以及NK细胞活性检测.检测两组的白介素-8（IL-8）、白介素-6（IL-6）及肿瘤坏死因子-α（TNF-α）水平.并观察56例肺结核合并重症肺炎患者中出院存活组（38例）和死亡组（18例）在出院或死亡当天的IL-6、IL-8、TNF-α的水平.结果 肺结核合并重症肺炎患者的CD＋3、CD＋4T淋巴细胞绝对值、CD＋4/CD＋8比值和NK细胞活性明显降低,而CD＋8T淋巴细胞增高,与健康对照组相比（P＜0.01）.肺结核合并重症肺炎组的IL-6、IL-8、TNF-α均高于健康对照组（P＜0.01）.而肺结核合并重症肺炎患者中存活组的IL-6、IL-8、TNF-α的水平显著低于死亡组.结论 肺结核合并重症肺炎患者T淋巴细胞免疫功能下降,从而影响患者的病情发展和疾病转归.     

红细胞免疫功能与AgNOR检测对肺结核病人的临床意义

为探讨肺结核病人免疫功能的检测方法，采用郭峰法及银染方法对肺结核病人与健康对照者红细胞免疫功能及外周血淋巴细胞核仁组成区相关嗜银蛋白（ＡｇＮＯＲ）进行测定。结果表明肺结核病人红细胞免疫功能与外周血淋巴细胞ＡｇＮＯＲ颗粒总面积（ＧＡ）与细胞核面积（ＮＡ）之比（ＧＡ／ＮＡ）均明显低于正常对照组（Ｐ＜０．０１）。表明此检测可作为结核病人细胞免疫功能的一种方法，为结核病病人的免疫治疗、判断预后提供依据。     

注射用母牛分枝杆菌预防性治疗潜伏性结核感染的细胞免疫机制

目的评价母牛分枝杆菌（微卡）在预防性治疗潜伏性结核感染中的细胞免疫学作用机理。方法对入学的大学新生进行PPD筛检和X线透视检查,确定潜伏结核感染人群,随机分为对照组、化学药物治疗组和微卡治疗组,每组中各随机选择30例,于用药前、用药后1个月、用药后6个月分别采集血样,采用流式细胞术检测符项细胞免疫学指标,动态观察三组免疫前后细胞免疫学指标的变化情况。结果治疗1个月后,微卡组外周血中CD3^＋、CD4^＋、CD8^＋、NK、NKT和γδT各细胞亚群的比例较之对照组普遍升高,各组IL4^＋、IFNγ^＋表达也显著升高;治疗6个月后,微卡组CD4^＋T细胞比例显著高于同期的对照组和化疗组;CD8^＋、γδT各细胞亚群的比例与用药后一个月相比呈下降趋势,其中CD8^＋T细胞与同期对照组比较下降显著;微卡组IL4^＋表达与同期化疗组、对照组比较显著性降低,同时IFNγ^＋表达较用药前水平显著升高。结论微卡能显著提高潜伏结核感染者固有和获得性细胞免疫水平,尤其是增高并维持CD4^＋细胞的比例,降低CD8^＋细胞的比例,并能够调节Th1／Th2平衡,提示微卡对潜伏性结核感染有预防性免疫治疗作用,避免潜伏结核感染者的发病。     

胃癌患者细胞免疫功能的变化及意义

应用流式细胞技术检测胃癌患者外周血T细胞亚群分布和自然杀伤（NK）细胞活性。结果与对照组相比,胃癌患者外周血CD3^＋、CD4^＋、NK细胞比例降低,CD8^＋细胞比例升高,CD4^＋/CD8^＋＋下降,而且升高或降低的程度与Borrm an分型和有无淋巴结转移相关。认为细胞免疫与胃癌发生、发展及预后密切相关,外周血T细胞亚群和NK细胞活性可作为监测胃癌病情变化的重要指标。     

细胞免疫介质辅助治疗重症肺结核疗效观察

目的观察重症肺结核采用细胞免疫介质辅助治疗疗效?方法细胞免疫介质4ml肌注,隔日一次?结果细胞免疫介质治疗继6个月末痰菌阴转率为92.1%,X线胸片病灶吸收率为89.5%,空洞闭合率为81.2%,P<0.05?结论二年后随访用细胞免疫介质治疗组二年随访无细菌学复发,对照组复发3例(8.8%),试验组细菌学控制速度优于对照组。     

人类免疫缺陷病毒合并结核分枝杆菌感染者的抗结核细胞免疫功能

目的 评价HIV合并结核分枝杆菌潜伏感染或合并活动性结核患者的抗结核细胞免疫功能.方法 应用早期分泌性抗原靶蛋白(ESAT)-6和培养滤出蛋白(CFP)-10诱导的结核酶联免疫斑点法对云南地区100例明确诊断的HIV感染者的血液标本进行结核分枝杆菌特异性T淋巴细胞检测,同时应用流式细胞仪检测外周血CD3+CD4+T淋巴细胞和CD3+CD8+T淋巴细胞的绝对计数水平.采用Mann-Whitney检验进行非参数统计分析.结果临床上无活动性结核感染证据的HIV感染者中合并结核分枝杆菌潜伏感染的感染率高达67.6%.HIV合并结核分枝杆菌潜伏感染者的外周血CD3+CD4+T淋巴细胞(532×106/L)和CD3+CD8+T淋巴细胞(473×106/L)绝对计数与单纯HIV感染者(406×106/L和504 × 106/L)相比,差异无统计学意义.HIV合并活动性结核感染者的外周血CD3+CD4+T淋巴细胞绝对计数平均值为189 × 106/L,CD3+CD8+T淋巴细胞绝对计数平均值为293×106/L,均显著低于单纯HIV合并结核潜伏感染组和HIV组(U=168.0,U=163.0;U=147.0,U=374.0;均P<0.01).HIV合并活动性结核感染者的ESAT-6和CFP-10抗原特异性斑点形成细胞数(31/106细胞和82/106细胞)显著低于HIV合并结核分枝杆菌潜伏感染者(92/106细胞和109/106细胞.U=507.0,U=529.5,均P<0.01).结论 我国无活动性结核临床证据的HIV感染人群中有较高的结核潜伏感染率,HIV合并活动性结核感染者的总体细胞免疫应答功能及特异性抗结核免疫应答功能均严重受损.     

乙型肝炎的细胞免疫功能研究的进展

机体免疫对决定急性乙型肝炎的临床表现及结局有重要意义。带抗原者常有免疫应答的低下,但对其引起免疫应答低下的具体环节及组织损害的确切机理仍然不够了解。最近对急性乙型肝炎病毒感染进行系统的细胞及体液免疫应答测定,发现以T细胞对前S抗原的应答出现最早,常于肝损害症象出现之前30日即已显现,此时血清HBeAg刚出现阳性。继而出现对核心抗原(HBcAg)的细胞及体液免疫应答。常于肝损害前10日出现对乙型肝炎表面抗原(HBsAg)的明显T细胞应答。临床症状出现后,上述细胞     

细胞免疫参数对结直肠癌的评估价值

目的:评估结直肠癌患者抗肿瘤免疫状态.方法:应用流式细胞术检测100例未转移结直肠癌患者、100例伴有转移结直肠癌患者和100例健康志愿者外周血CD4+、CD8+、NK、B、CD4+CD25HighCD127lowTreg、Th/Treg值,采用单因素方差分析进行比较,分析差异.结果:转移性结直肠癌患者组分别与正常对照组和非转移性结直肠癌患者组相比,CD4+CD25HighCD127lowTreg细胞升高(7.72%±2.20%vs6.08%±1.47%,5.91%±1.55%,均P<0.05),CD4+T细胞降低(34.04%±8.71%vs37.83%±7.62%,37.68%±8.89%,均P<0.05),Th/Treg值降低(4.70±1.72vs6.47±2.54,6.81±4.09,均P<0.05).结直肠癌患者与正常对照组CD8+T细胞、NK细胞、B细胞三组两两相比,均无统计学意义.结论:转移性结直肠癌患者免疫功能紊乱,主要表现为CD4+T细胞、Th/Treg值降低,CD4+CD25HighCD127lowTreg细胞升高.     

HIV/AIDS人群中肺结核患者的治疗效果与细胞免疫的相关性研究

目的了解HIV/AIDS人群中肺结核(HIV(+)TB(+))患者的免疫特征及抗结核治疗的效果。方法横断面收集12例现症HIV(+)TB(+)患者、24例HIV/TB双重感染者(HIV(+)PPD(+))、74例单纯HIV/AIDS患者(HIV(+)PPD(-))、56例单纯肺结核病患者(HIV(-)TB(+))(初治涂阳)及36例正常对照者的外周血2 ml,进行淋巴细胞亚群的比较。同时前瞻性收集12例HIV(+)TB(+)患者及56例HIV(-)TB(+)患者的血常规数据、药物不良反应的发生、痰菌阴转及肺部病变的改变进行抗结核治疗的效果分析。结果(1)与正常人群相比,HIV感染或结核感染均可导致患者的淋巴细胞亚群不同程度的下降(P<0.05)。(2)在HIV与结核双重感染人群的细胞免疫中,与HIV相关的免疫改变起主要作用:不管其是否结核发病,其淋巴细胞计数都存在同等程度的下降。(3)HIV(+)TB(+)患者的抗结核治疗效果较好:与HIV(-)TB(+)患者相比,药物不良反应、痰菌阴转及肺部病变的改变无显著性差异(P>0.05)。结论HIV(+)TB(+)患者的细胞免疫主要与HIV感染有关,而有效的抗结核药物治疗可提高HIV(+)TB(+)患者的细胞免疫功能,并可使其肺结核病得到良好的控制。     

HIV/AIDS人群中肺结核患者的治疗效果与细胞免疫的相关性研究

目的了解HIV/AIDS人群中肺结核(HIV(+)TB(+))患者的免疫特征及抗结核治疗的效果。方法横断面收集12例现症HIV(+)TB(+)患者、24例HIV/TB双重感染者(HIV(+)PPD(+))、74例单纯HIV/AIDS患者(HIV(+)PPD(-))、56例单纯肺结核病患者(HIV(-)TB(+))(初治涂阳)及36例正常对照者的外周血2 ml,进行淋巴细胞亚群的比较。同时前瞻性收集12例HIV(+)TB(+)患者及56例HIV(-)TB(+)患者的血常规数据、药物不良反应的发生、痰菌阴转及肺部病变的改变进行抗结核治疗的效果分析。结果(1)与正常人群相比,HIV感染或结核感染均可导致患者的淋巴细胞亚群不同程度的下降(P&lt;0.05)。(2)在HIV与结核双重感染人群的细胞免疫中,与HIV相关的免疫改变起主要作用:不管其是否结核发病,其淋巴细胞计数都存在同等程度的下降。(3)HIV(+)TB(+)患者的抗结核治疗效果较好:与HIV(-)TB(+)患者相比,药物不良反应、痰菌阴转及肺部病变的改变无显著性差异(P&gt;0.05)。结论HIV(+)TB(+)患者的细胞免疫主要与HIV感染有关,而有效的抗结核药...     

The relationship between absolute counts of lymphocyte subsets and clinical features in patients with pulmonary tuberculosis

BackgroundThe aim of the present study is to investigate the clinical value and characteristics of peripheral blood lymphocyte subsets in patients with pulmonary tuberculosis (PTB) using flow cytometry.MethodsThe absolute counts of T, CD4⁺T, CD8⁺T, natural killer (NK), NKT and B lymphocytes in 217 cases of PTB were detected, and the variations in lymphocyte subset counts between different ages and genders and between aetiological detection results and chest radiography results were analysed.ResultsIn 75.3% of the patients with PTB, six subset counts were lower than the normal reference range, and 44% showed lower‐than‐normal CD4⁺T lymphocyte levels. The counts of T, CD4⁺T, CD8⁺T and B lymphocytes were significantly lower in patients aged >60 years, and the NKT cell counts were significantly lower in female patients than in male patients. Among the patients with positive aetiological results, 40.8% had reduced CD8⁺T counts; these were significantly lower than those in patients with negative aetiological results (P = 0.0295). The cell counts of T, CD4⁺T, CD8⁺T and B lymphocytes reduced as lesion lobe numbers increased. The counts of T, CD4⁺T and CD8⁺T lymphocytes were significantly higher in the group with lesions affecting one lobe than in the groups with two to three lobes or four to five lobes, and the counts of B lymphocytes were significantly higher in the group with one lobe and the group with two to three lobes than in the group with four to five lobes. The counts of CD4⁺T and CD8⁺T lymphocytes were highest in the no cavity group and showed a downward trend with the increase in cavities; the T lymphocyte count was significantly higher in the no cavity group than in the group with five or more cavities (P = 0.014), and the CD8⁺T lymphocyte count was significantly higher in the no cavity group than in the group with one to two cavities and the group with five or more cavities (P = 0.001 and 0.01, respectively).ConclusionsIn most patients with tuberculosis, immune function is impaired. The absolute counts of peripheral blood lymphocyte subsets are closely related to the aetiological results and lesion severity in patients with PTB; this could be used as evidence for immune intervention and monitoring curative effects.     

Friends and foes of tuberculosis: modulation of protective immunity

Protective immunity in tuberculosis (TB) is subject of debate in the TB research community, as this is key to fully understand TB pathogenesis and to develop new promising tools for TB diagnosis and prognosis as well as a more efficient TB vaccine. IFN‐γ producing CD4⁺ T cells are key in TB control, but may not be sufficient to provide protection. Additional subsets have been identified that contribute to protection such as multifunctional and cytolytic T‐cell subsets, including classical and nonclassical T cells as well as novel innate immune cell subsets resulting from trained immunity. However, to define protective immune responses against TB, the complexity of balancing TB immunity also has to be considered. In this review, insights into effector cell immunity and how this is modulated by regulatory cells, associated comorbidities and the host microbiome, is discussed. We systematically map how different suppressive immune cell subsets may affect effector cell responses at the local site of infection. We also dissect how common comorbidities such as HIV, helminths and diabetes may bias protective TB immunity towards pathogenic and regulatory responses. Finally, also the composition and diversity of the microbiome in the lung and gut could affect host TB immunity. Understanding these various aspects of the immunological balance in the human host is fundamental to prevent TB infection and disease.     

肺结核和肺外结核患者外周血淋巴细胞亚群的检测意义探讨

目的探讨肺结核与肺外结核患者外周血淋巴细胞亚群的检测意义。方法选择72例结核病患者,其中肺结核患者41例(A组),肺外结核患者31例(B组),同期选择32例健康体检者作为对照组(C组),应用流式细胞术即(FCM)进行检测。结果三组外周血淋巴细胞亚群的表达率比较,有统计学意义(P0.05),三组在CD+3CD+4/CD+3CD+8比值比较,差异无统计学意义(P0.05)。结论肺结核与肺外结核患者行外周血淋巴细胞亚群的检测对分析免疫状态有重要意义。     

老年与青年肺结核患者免疫功能差异的探讨

目的：探索老年肺结核患者与青年肺结核患者细胞免疫和体液免疫的各自特点以及两者的差异和相关免疫指标的临床意义。方法检测175例老年肺结核患者（老年组）和151例中青年肺结核患者（中青年组）免疫功能,并与50例健康人群（健康组）进行比较分析。采用流式细胞术（ FCM）检测肺结核患者和健康人群外周血CD3＋T细胞、CD4＋T细胞、CD8＋T细胞、NK细胞、B细胞比率;采用免疫透射比浊法测定免疫球蛋白水平。结果老年组CD3＋、CD4＋细胞与中青年组和健康组比较明显降低,差异有统计学意义（ P＜0?01）。中青年组CD4＋、CD8＋T细胞比率明显高于健康组,差异有统计学意义（ P＜0?01）。 NK细胞老年组最高、健康组次之、中青年组最低,3组间差异均有统计学意义（ P＜0?01）。老年和中青年肺结核患者血清IgA均高于健康组,差异有统计学意义（ P＜0?01）。结论中青年肺结核患者免疫功能明显高于健康人群,免疫效应细胞以CD4＋、CD8＋T细胞为主。老年肺结核患者的细胞免疫功能明显低于健康人群,免疫效应细胞以NK细胞为主。青年肺结核患者与老年肺结核患者在体液免疫功能方面无明显差异。     

Trained immunity: a new avenue for tuberculosis vaccine development

Adaptive immunity towards tuberculosis (TB) has been extensively studied for many years. In addition, in recent years the profound contribution of innate immunity to host defence against this disease has become evident. The discovery of pattern recognition receptors, which allow innate immunity to tailor its response to different infectious agents, has challenged the view that this arm of immunity is nonspecific. Evidence is now accumulating that innate immunity can remember a previous exposure to a microorganism and respond differently during a second exposure. Although the specificity and memory of innate immunity cannot compete with the highly sophisticated adaptive immune response, its contribution to host defence against infection and to vaccine‐induced immunity should not be underestimated and needs to be explored. Here, we present the concept of trained immunity and discuss how this may contribute to new avenues for control of TB.     

Significance of the frequency of CD4+CD25+CD127- T-cells in patients with pulmonary tuberculosis and diabetes mellitus

Background and objective: Pulmonary tuberculosis and diabetes mellitus (DM) are closely associated. The objective of this study was to determine whether the expression of CD4+CD25+CD127? T‐cells (regulatory T‐cells (Treg)) is associated with diabetic pulmonary tuberculosis. Methods: Flow cytometry was used to determine the frequencies of CD4+CD25+ and CD4+CD25+CD127? T‐cells in peripheral blood, bronchoalveolar lavage fluid (BALF) and pleural effusions from 120 patients (30 with pulmonary tuberculosis and DM (TBDM), 30 with pulmonary tuberculosis without DM (TB), 30 with tuberculous pleurisy without DM (TBP) and 30 healthy volunteers). The concentrations of interferon (IFN)‐γ and interleukin (IL)‐10 in BALF and pleural effusions were determined by enzyme‐linked immunosorbent assay. Results: Treg frequencies in peripheral blood were significantly higher in patients with TBDM, TB and TBP than in the control group, with the frequency in TBDM being the highest (P < 0.01 for all). In TBP patients, Treg frequencies were significantly lower in pleural effusions than in peripheral blood. In TB patients, Treg frequencies in BALF and peripheral blood were not significantly different. However, in TBDM patients, Treg frequencies were significantly higher in BALF than in peripheral blood. IL‐10 expression was significantly higher, and IFN‐γ expression was significantly lower in BALF of TBDM patients compared with BALF and pleural effusions of TB patients. Conclusions: In patients with pulmonary tuberculosis and DM, the imbalance between Treg and effector T‐cells at pathological sites may be associated with weakened immunity and clinical manifestations of TB.     

CD4+CD25+调节性T细胞对肺结核患者特异细胞免疫的调节作用

目的　探讨调节性T细胞对结核患者特异性细胞免疫的调节作用及其在结核病发生中的意义。方法 采用免疫磁珠从健康对照和结核患者外周血单个核细胞中分离CD4⁺CD25⁺调节性T细胞,观察其对结核患者外周血免疫反应,包括细胞增殖反应和细胞因子IFN-γ及IL-10分泌的影响。结果 体外消除CD4⁺CD25⁺调节性T细胞没有显著影响健康对照PBMC对BCG抗原的增殖反应,但可以显著增强结核患者PBMC对BCG抗原的细胞增殖反应、细胞因子IFN-γ及IL-10的分泌。分离的CD4⁺CD25⁺调节性T细胞能显著抑制结核患者CD4⁺CD25^-T细胞对BCG抗原及抗-CD3的细胞增殖和细胞因子IFN-γ分泌;CD4⁺CD25⁺调节性T细胞也抑制BCG刺激的CD4⁺CD25^-T细胞IL-10的分泌,但不影响抗-CD3刺激的IL-10分泌。结论 CD4⁺CD25⁺调节性T细胞可能通过抑制结核患者特异性细胞免疫应答促进肺结核病的发生发展。     

HIV合并结核潜伏感染患者CD_4~+细胞免疫功能影响的研究

目的观察HIV合并结核潜伏感染患者CD+4细胞免疫功能影响。方法选取136例HIV感染者,分别进行PPD和ELISPOT检测确定HIV合并结核潜伏感染者,随后通过流式细胞术检测治疗前后患者CD+4细胞的变化。结果 PPD试验对结核菌抗原阳性反应为3.4%;ELISPOT检测阳性率为20.6%,高于PPD皮试阳性率。流式结果显示HIV感染患者CD+4细胞数小于50/μl共有25例,51-200/μl有64例,大于200/μl有47例,各组ELISPOT检测阳性率分别为4%,28.1%和14.9%。9例HIV合并结核潜伏感染患者治疗9个月后,ELISPOT检测斑点中位数减少61.6%。结论 HIV合并结核潜伏感染者CD+4细胞明显降低,且普遍低于200/μl。