应用人型单克隆抗体治疗感染疾病

<正> 接受免疫仰制剂治疗癌症、重度烧伤等免疫功能低下的患者,常招致严重的绿脓杆菌(P、aeruginosa)感染。此外,可对现有抗生素很快产生抗药性,用化学疗法很难治疗。 Millican等(1958年)首次报道抗绿脓杆菌免疫血清抗体疗法有实用价值。以后,许多作者对抗绿脓杆菌各种成分的抗体进行了深入研究,结果发现脂多糖(LPS,存在于菌体外膜)抗体,可借助吞噬细胞的免疫吞噬作用而感染。用鼠型单克隆抗体(McAp)试验也有同样的结果,并发现抗外膜蛋白McAp的防御感染作用比抗LPSMcAp效果差。 最近,制备抗绿脓杆菌脂多糖的人型McAp已获成功,产生人型McAp的细胞是采用Epstein-Barr病毒(EBV)转化法或杂交细胞瘤法。作者对健康人未梢血淋巴细胞的病毒转化细胞产生的抗绿脓杆菌人型     

流行性出血热(EHF)Ⅱ型(家鼠型)纯化灭活疫苗Ⅰ期临床观察

根据卫生部(91)特申体第02号文,92年完成了Ⅱ型纯化疫苗Ⅰ期临床反应及血清效果观察,免疫程序为0,1,2月,分原倍疫苗组和1∶2稀释组,各免15人,每针次免疫后连续观察3天,结果均无不良反应,仅在注射时稍有微胀痛感。二针次免疫后均能产生较高的免疫抗体:原倍疫苗免疫抗体滴度,ELISA1∶181(GET),PRNT中和抗体≥1∶10;1∶2稀释疫苗,ELISA1∶169(GMT),PRNT≥1∶10。三针次免疫后抗体滴度高于二针次;原倍疫苗,ELISA1∶478(GMT),PRNT1∶10～1∶20;稀释疫苗,ELISA1∶446(GMT),PRNT1∶10～1∶20,但原倍疫苗和稀释疫苗的抗体水平之间无显著性差异。半年后仍保持一定抗体水平。可采用二针次总量2ml免疫。     

中国婴儿中脊灰母传抗体水平对两种疫苗免疫效果的影响

为了了解2月龄婴儿中针对脊髓灰质炎病毒的中和抗体水平,并探讨母传抗体对脊髓灰质炎减毒活疫苗(OPV)和灭活疫苗(IPV)免疫效果的影响。对416名2月龄婴儿分别接种OPV和IPV,采集免疫前后血清,用微量中和法检测血清中Ⅰ、Ⅱ、Ⅲ型脊髓灰质炎病毒中和抗体滴度,评价抗体GMT水平及4倍增长情况。检测结果显示,2月龄婴儿母传抗体Ⅰ、Ⅱ、Ⅲ型阳性率分别为45%、38.2%和17.5%,抗体GMT水平为9.0、8.1和5.2。经接种两组疫苗后,母传抗体阳性者与阴性者免后抗体GMT水平相比,OPV组无明显差异,IPV组阳性者略低于阴性者。在免前抗体滴度<1∶32人群中,OPV组免后抗体滴度4倍增长率及几何滴度增长倍数分别为:Ⅰ型93.6%、71.2;Ⅱ型98.2%、43.7;Ⅲ型91.7%、47.9;IPV组免后抗体滴度4倍增长率及几何滴度增长倍数分别为:Ⅰ型82%、9.4;Ⅱ型62.8%、5.1;Ⅲ型95.6%、11.7;在免前抗体滴度1∶32～1∶128人群中,OPV组Ⅰ型92.3%、23;Ⅱ型86.4%、13.9;Ⅲ型55.6%、4.1;IPV组Ⅰ型48%、2.5;Ⅱ型15%、0.9;Ⅲ型55.6%、2.7。目前中国2月龄婴儿免前脊灰抗体阳性率较高,尤其是Ⅰ、Ⅱ型。脊灰母传抗体对两种疫苗免疫效果有一定干扰,对IPV疫苗的影响较为明显。     

2018年河南省健康人群脊髓灰质炎抗体水平监测结果分析

目的了解2018年河南省健康人群脊髓灰质炎(poliomyelitis,简称脊灰)抗体水平,为评价脊灰疫苗免疫效果、保持河南省无脊灰状态提供科学依据。方法选取漯河市舞阳县、许昌市建安区和濮阳市清丰县作为监测点,通过中和抗体测定法对健康人群进行脊灰抗体检测。结果共检测636份健康人血标本,其中脊灰I型和III型抗体阳性率分别为96.54%和93.55%,抗体几何平均滴度(geometric mean titer,GMT)分别为1∶137.70和1∶47.27,I型、III型抗体阳性率和GMT之间差异均有统计学意义(P0.05),I型抗体阳性率和GMT均高于III型。不同年龄组之间脊灰I型、III型抗体阳性率和GMT差异均有统计学意义(P0.05),GMT随着年龄的增加而降低。不同免疫史之间脊灰I型、III型抗体阳性率和GMT差异有统计学意义(P0.05),接种过脊灰疫苗人群的抗体阳性率和GMT均高于未接种或者免疫史不详人群。不同性别和不同地区之间脊灰I型、III型抗体阳性率和GMT差异均无统计学意义(P0.05)。结论 2018年河南省健康人群脊灰抗体处于较高水平,已形成了有效的免疫屏障,但保持河南省无脊灰的发生工作依然严峻。脊灰防治需加强人群的疫苗免疫规划和常规免疫,定期对健康人群脊灰抗体的检测是防止脊灰病毒传播较为有效的方法之一。     

2002~2004年兰州市流感疫苗免疫效果分析

2002~2004年每年9~11月在兰州市对我省使用流感疫苗进行血清学考核,3年用血凝抑制试验(H I)分别检测44、52、49人疫苗免疫前后不同4种血清型流感病毒的抗体水平。结果显示,接种疫苗者30~35 d后流感病毒4个血清型流感病毒H I抗体均有不同程度的增长,H1N1、H3N2、B(Yam agata)、B(V ictorian)保护率(≥1∶40)分别为91.72%、91.72%、81.63%和59.38%;免疫后人体H I抗体滴度的几何均数(GMT)分别为1∶221.76、1∶189.58、1∶71.04和1∶43.04;较接种前H I抗体滴度≥4倍的分别占53.79%(78/145)、58.62%(84/145)、75.51%(37/49)和58.37%(56/96)。血清学检测表明流感疫苗免疫效果好,免疫成功率高。     

甲型H1N1流感病毒裂解疫苗的免疫原性和安全性

目的评价甲型H1N1流感病毒裂解疫苗(简称甲型H1N1流感疫苗)的免疫原性和安全性。方法按照随机、双盲、安慰剂对照的原则,采用0、21天免疫程序,选择3岁及3岁以上健康者1 202人。分组为3~11岁、12~17岁、≥60岁组,按照人数基本为1∶1的比例随机分别接种7.5μg和15.0μg甲型H1N1流感疫苗;18~59岁组按照人数基本为1∶1∶1的比例随机分别接种7.5μg、15.0μg甲型H1N1流感疫苗和安慰剂对照。观察各组接种后的不良反应率以及免疫前后血凝抑制(HI)抗体阳转率、保护率、GMT水平和平均增长倍数。结果受试对象的安全性结果显示7.5μg和15.0μg组不良反应发生率分别为8.74%(48/549)和13.88%(74/533),其中Ⅱ级反应率分别为0.36%(2/549)和1.13%(6/533),未观察到Ⅲ级及以上不良反应和其他异常反应及严重不良事件。2剂接种未见不良反应叠加现象。7.5μg或15.0μg试验疫苗首剂免疫后,血清抗体阳性率分别为85.13%(395/464)和90.77%(413/455),保护率分别为85.56%(397/464)和91.43%(416/455),抗体GMT较免疫前分别增长36.1倍和52.6倍。2剂免疫后,血清抗体阳性率分别是97.84%(454/464)和99.12%(451/455),保护率分别是98.06%(455/464)和9 9.56%(453/455),抗体GMT较免疫前分别增长63.3倍和96.0倍。4个年龄组(3~11岁、12~17岁、18~59岁及≥60岁年龄组)7.5μg和15.0μg组HI抗体阳性率和保护率均大于70%,GMT较免疫前均增长2.5倍以上,结果显示7.5μg和15.0μg甲型H1N1流感疫苗接种1剂后抗体水平已达到研究方案中设定的预期标准,免疫2剂后抗体阳性率和抗体水平明显提高。结论临床试验表明甲型H1N1流感疫苗具有良好的安全性和免疫原性,且接种1剂15.0μg甲型H1N1流感疫苗,即可在3岁和3岁以上人群中产生良好的免疫效果。     

流感病毒裂解疫苗临床安全性和免疫原性研究

目的了解流感病毒裂解疫苗的安全性和免疫原性。方法按整群随机抽样原则,对上海市200名18~60岁健康成人进行疫苗接种后临床安全性指标(局部反应、全身反应)的监测。用微量血凝抑制试验检测血清HI抗体,比较血清抗体阳转率、抗体几何平均滴度(GMT)和增长倍数。结果接种疫苗72 h内局部反应率为7.00%;全身反应率为12.00%,其中发热反应率为7.50%,其他全身反应率为4.50%;均以轻度反应为主。H1N1、H3N2和B型免疫后抗体阳转率分别为63.49%、74.07%和56.08%,抗体GMT分别为1∶170.10、1∶128.85和1∶446.79,免疫后比免疫前分别增长到6.93倍、8.72倍和4.90倍。结论此流感病毒裂解疫苗的临床安全性和免疫原性均较好。     

E.tenella感染雏鸡特异性抗体的动态变化和母源免疫的研究

本实验用斑点酶联免疫试验 (Dot ELISA)检测了E .tenella感染雏鸡特异性抗体、免疫母鸡卵黄和后代血清中特异性母源抗体的动态变化及不同日龄雏鸡的抗球虫水平。结果表明 :(1)雏鸡感染E .tenella后第 6d即可在循环血液中检测到特异性IgG ,于第 18天达到峰值 ,第 30天降至感染后第 7天时的水平。 (2 )母鸡二次免疫后第 5天卵黄中即有高水平的母源抗体 ,免疫母鸡后代 1日龄时母源抗体滴度高达 9.83,与未免疫对照组差异极显著 (P <0 .0 1) ,二者都随着日龄增长降低 ,但免疫组下降幅度很小 ,2 9日龄时仍和对照组 18日龄水平相当。 (3)免疫母鸡后代对再感染的抵抗力显著增强 ,卵囊减少率高达 93%,抗球虫指数和相对增重率都与对照组差异极显著 (P <0 .0 1) ,雏鸡的抗球虫水平随着日龄增长逐渐降低 ;母源抗体、抗球虫指数和相对增重率三者之间两两呈现明显的正相关 ,而这三者又都与卵囊产量呈明显的负相关。     

应用ELISA法检测人群中幽门螺杆菌抗体及血清流行病学分析

应用酶联免疫吸附试验(ELISA)对307例自然人群和228例胃病患者的血清进行了抗幽门螺杆菌(HP)抗体的检测,同时与尿素酶试验和涂片镜检结果比较。结果:自然人群中HP抗体阳性率为14.66％,不同性别、职业、民族间HP抗体的阳性率无差异。各年龄组间HP抗体阳性率有随年龄增加而升高趋势。胃病患者HP抗体阳性率为61.41％,GMT为1:430.53,明显高于自然人群的14.66％,GMT 1:15783,两者差异显著。ELISA法与尿素酶试验和涂片镜检结果存在相关关系。认为ELISA法结果可靠,可用于人群普查及HP感染的诊断。     

建立膜抗原荧光抗体试验评价北京株冻干水痘疫苗免疫效果

为了建立用于水痘疫苗接种后血清中特异性抗体检测的膜抗原荧光抗体(FAMA)法,并对接种水痘疫苗后儿童血清中水痘特异性抗体进行检测,评价北京株水痘疫苗的免疫效果。以水痘带状疱疹病毒(VZV)感染细胞作为抗原制备成固定抗原玻片,以异硫氰酸荧光素(FITC)标记的羊抗人IgG作为二抗建立FAMA法,并对该法的敏感性、特异性进行验证。运用此法对不同剂量北京株水痘疫苗接种后儿童血清中特异性抗体进行检测,分析儿童血清中水痘特异性抗体水平以及免后抗体阳转率,并与Oka株水痘疫苗进行比较。结果显示,FAMA法敏感性可达0.0196IU/ml,特异性好。应用此法检测300名观察者免前免后双份血清样本中抗VZVIgG,易感者中北京株水痘疫苗原苗(39810PFU/0.5ml)、2000PFU/0.5ml、500PFU/0.5ml接种组儿童血清免后抗体阳转率分别为100%、98.77%、85.42%,抗体几何平均滴度(GMT)分别为36.4、34.3、18.6,原苗与2000PFU间的抗体阳转率和GMT均无显著性差异(P>0.05),但原苗与500PFU、2000PFU与500PFU间的抗体阳转率和GMT均有显著性差异(P<0.05)。对照国产、进口Oka株水痘疫苗接种后抗体阳转率分别为95.35%、96.97%,抗体GMT分别为13.3、16.0,不同剂量北京株疫苗抗体阳转率与国产、进口Oka株疫苗相比,差别无显著性(P>0.05),但北京株疫苗原?     

The antibacterial immunity of people under dynamic observation in an altered radiation situation]

The comparative study of the isolation rate, level, antigenic and class specificity of serum antibodies to the causative agents of purulent septic infections (Staphylococcus aureus, Pseudomonas aeruginosa, Proteus mirabilis) and acute enteric infections in healthy adults with different ABO blood groups before (836 persons) and after (1,429 persons) the catastrophe at the Chernobyl nuclear power station was made. The study revealed the fact that the genesis of antibodies directed against different microorganisms can be stimulated without additional antigenic challenge in the form of disease or immunization, which was definitely indicative of the influence of small radiation doses in Kiev on the humoral immunity of the population. The multifactor character of the dependence of antibacterial antibody formation under altered radiation conditions on the specific features of the infective agent and the intensity of its circulation among the population, individual immune responsiveness of the body and concrete radiation conditions was established.     

Humoral immunity and output of first-stage larvae of Elaphostrongylus rangiferi (Nematoda, Metastrongyloidea) by infected reindeer, Rangifer tarandus tarandus

The use of an indirect immunofluorescence technique demonstrated that serum from reindeer, Rangifer tarandus tarandus, infected with Elaphostrongylus rangiferi (Nematoda, Metastrongyloidea) contained antibodies directed against antigen(s) on the cuticle of the parasites first-stage larvae (L1). Output of L1 from the male reindeer was low in the period June to August, but increased to a higher level during the rutting season (September to October). The titre of specific antibody showed an inverse pattern. In the female reindeer, larval output remained high throughout the sampling period from January to July. During this period antibody titre was low. A relationship between stress (rutting season or calving period), immunity and larval output is suggested.     

Results of using polyvalent Pseudomonas aeruginosa vaccine in children with burns by various medical centers

Polyvalent Pseudomonas aeruginosa vaccine, prepared at the Institute of Hematology from 10 hospital strains isolated from burn wounds, was administered to 32 children with extensive and deep burns. The vaccine was well tolerated. The vaccine produced a high degree of the immunity against Pseudomonas aeruginosa infection. Agglutinin serum titre increased significantly. Vaccination either prevented or inhibited the infection of burn wounds with Pseudomonas aeruginosa in all immunized children. The symptoms of Pseudomonas aeruginosa infection usually disappeared following one or two vaccinations. Bacteriemia caused by P. aeruginosa was not observed in 31 out of 32 children. In the remaining child transient bacteriemia was noted. No septicemia caused by P. aeruginosa was seen. Due to the high efficiency of the polyvalent P. aeruginosa vaccine all burned children with burns exceeding 10% of the total body surface should by vaccinated to prevent the life-threatening infections with Pseudomonas aeruginosa.     

体育运动和脂质代谢

一般健康人总胆固醇(T-Ch)、甘油三酯(TG)、高密度和低密度脂蛋白胆固醇(HDL-ch,LDL-cH)的含量随年令而增加。中年组(45-59)HDL-Ch平均值较低,男比女低,这与中国人男性45岁以后患冠心病(CHD)多于女性相吻合。冠心病及脑中风患者的HDL-ch含量比健康人低(P<0.05)。运动员的HDL-Ch含量明显高于一般健康人(P<0.01),其均值且高于不易患动脉粥样硬化(AS)的八种哺乳动物的均值(60.40mg/d1)。运动员的T-ch、TG和HDL-Ch含量低于健康人。     

Effects of dietary supplementation of potential probiotic Pseudomonas aeruginosa VSG-2 on the innate immunity and disease resistance of tropical freshwater fish, Labeo rohita

The effects of dietary Pseudomonas aeruginosa VSG-2 supplementation on innate immunity and protection against Aeromonas hydrophila infection were evaluated in Labeo rohita. Fish were fed for 60 days with control diet or 3 experimental diets containing P. aeruginosa VSG-2 at 10(5), 10(7), and 10(9) cfu g(-l), respectively. Various innate immune parameters were examined at 30 and 60 days post-feeding. Fish were challenged with A. hydrophila 60 days post-feeding and mortalities were recorded over 10 days post-infection. Dietary supplementation of P. aeruginosa VSG-2 significantly increased serum lysozyme and alternative complement pathway (ACP) activities, phagocytosis, and respiratory burst activity in head kidney macrophages of L. rohita throughout the experimental period. Superoxide dismutase (SOD) activity significantly increased after 60 days in the groups fed diets containing 10(7) and 10(9) cfu g(-1) P aeruginosa. Serum IgM levels were significantly higher in the treatment groups than in the control group after 30 days of feeding; however, the opposite result was observed at 60 days. Moreover, fish fed diets containing 10(7) and 10(9) cfu g(-1)P. aeruginosa had significantly higher post-challenge survival rates against A. hydrophila infection. Further, P. aeruginosa VSG-2 was found to be safe for mammals. These results indicate that dietary P. aeruginosa VSG-2 supplementation at 10(7) cfu g(-1) can effectively improve innate immunity and disease resistance in L. rohita.     

铜绿假单胞菌菌苗预防白色念珠菌感染的实验研究

目的利用铜绿假单胞菌菌苗探索阻断白色念珠菌感染的影响。方法家兔耳皮内注射白色念珠菌,进行活菌攻击,建立动物感染模型。观察用铜绿假单胞菌菌苗免疫的家兔状况;用试管凝集法测定家免的抗体效价;采用小白鼠体内吞噬法测定免疫组和空白对照组巨噬细胞的吞噬百分率和吞噬指数,以得出铜绿假单胞菌菌苗的免疫性。结果观察发现：与对照组比较,铜绿假单胞菌菌苗免疫组抗体效价,巨噬细胞的吞噬能力明显提高;注射区局部感染及全身症状明显减轻;肾脏感染灶减少,病理切片显示病情较轻。结论铜绿假单胞菌菌苗能够减轻注射区局部感染及全身症状,对肾脏的播散性白色念珠菌感染具有一定的阻断作用。     

Female and male genetic contributions to post-mating immune defence in female Drosophila melanogaster

Post-mating reduction in immune defence is common in female insects, and a trade-off between mating and immunity could affect the evolution of immunity. In this work, we tested the capacity of virgin and mated female Drosophila melanogaster to defend against infection by four bacterial pathogens. We found that female D. melanogaster suffer post-mating immunosuppression in a pathogen-dependent manner. The effect of mating was seen after infection with two bacterial pathogens (Providencia rettgeri and Providencia alcalifaciens), though not after infection with two other bacteria (Enterococcus faecalis and Pseudomonas aeruginosa). We then asked whether the evolution of post-mating immunosuppression is primarily a ‘female’ or ‘male’ trait by assaying for genetic variation among females for the degree of post-mating immune suppression they experience and among males for the level of post-mating immunosuppression they elicit in their mates. We also assayed for an interaction between male and female genotypes to test the specific hypothesis that the evolution of a trade-off between mating and immune defence in females might be being driven by sexual conflict. We found that females, but not males, harbour significant genetic variation for post-mating immunosuppression, and we did not detect an interaction between female and male genotypes. We thus conclude that post-mating immune depression is predominantly a ‘female’ trait, and find no evidence that it is evolving under sexual conflict.     

流行性腮腺炎疫苗免后血清学效果及免疫方案探讨

选以往无流行性腮腺炎患病史和接种史的学龄及学龄前儿童２４３名,血清检测流腮ＨＩ抗体,阳性率为５５．６％,阳性率明显地随年龄增大而上升,而性别无差异。经用Ｓ生物所及Ｂ生物所生产的两种疫苗接种,免后ＨＩ抗体的跳高率及ＧＭＴ均较免前有明显上升。双份血清检测结果,免后ＨＩ抗体显著跳高率（≥４倍）为４４．８％;９８名免前阴性儿童免后ＨＩ阳转率５７．１％,ＧＭＴ为１１３．２９,两种疫苗均无显著差异,提示疫苗的质量和稳定性有待提高,笔者对当前免疫方案提出了改进意见。     

Bactericidal activity of human, swine and cattle serum against pseudomonas aeruginosa strains

The aim of this study was to assess of bactericidal activity of human, swine and cattle serum against 136 of Pseudomonas aeruginosa strains isolated from people, fishes, domestic and fur animals. The mechanism of the bactericidal activity of serum against gram-negative bacteria is complex and involves the participation of complement, antibodies and lysozyme (1, 5, 7, 8, 10, 11, 13, 14, 24, 25, 27, 30). The susceptibility of gram-negative rods to serum is differentiated. Pseudomonas aeruginosa strains are the most resistant (17, 25, 30). This opportunistic pathogen produce proteases that destroy complement components and immunoglobulins (3, 18, 19). The bactericidal activity of serum was determined after 3 hours incubation of bacteria in 50% serum by the method of Jankowski (1981) (5). The results of this study indicate that 71% of this strains were resistant to swine serum action, 68% of this strains were resistant to bovine serum and 57% of the Pseudomonas aeruginosa strains were sensitive to human serum. The P. aeruginosa strains isolated from fishes were the most sensitive to serum action and the strains isolated from people and cattle were most resistant to the bactericidal activity of serum.     

In vitro T cell-mediated killing of Pseudomonas aeruginosa. I. Evidence that a lymphokine mediates killing

Previous studies have demonstrated in vivo that T cells can provide protective immunity, in the absence of antibody, against infection with the extracellular Gram-negative bacterium Immunotype 1 (IT-1) Pseudomonas aeruginosa. We established an in vitro system in which immune T cells, after reexposure to bacterial antigens and to macrophages, secrete a product that kills the bacteria. Although macrophages are required for in vitro killing, they function neither as antigen-presenting nor as phagocytic cells in this system. T cells from animals immunized against a different P. aeruginosa immunotype will not kill IT-1 organisms; but the supernatants produced by IT-1 immune T cells after exposure to macrophages and IT-1 P. aeruginosa organisms are nonspecifically effective in killing unrelated bacteria. Because the supernatants from immune T cells lose their bactericidal properties upon minimal dilution, we conclude that if this mechanism is active in vivo, it must play a role in local immunity.