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1.
慢性乙型肝炎树突状细胞表型和功能的变化与免疫耐受   总被引:5,自引:0,他引:5  
目的 观察慢性乙型肝炎病毒(HBV)感染者树突状细胞(DC)形态和功能的改变。方法 从13例慢性乙型肝炎患者和11例健康人外周血中分离和培养DC,观察DC的形态,用流式细胞仪检测DC表面标记HLA-DR、CD1a、CD80和CD86的表达,用^3H-TdR掺入法测定DC诱导混合性淋巴细胞反应(MLR)的能力。结果 正常DC较慢性乙型肝炎患者在形态上更为典型,不规则,HLA-DR、CD80和CD86分子的表达水平较高(P<0.05),诱导MLR的能力较强(P<0.05)。结论 慢性乙型肝炎患者外周血DC处于不完全成熟状态,其免疫刺激能力较低。  相似文献   

2.
目的 研究慢性乙型肝炎患者外周血树突状细胞(DC)经HBsAg、HBcAg活化后的免疫功能.方法 从慢性乙型肝炎患者外周血中培养扩增DC,在DC成熟前,加入纯的HBsAg、HBcAg刺激,用流式细胞仪检测DC表型,用液闪计数仪观察DC对T细胞的增殖作用,用ELISA法检测混合淋巴细胞反应(MLR)中细胞因子的分泌水平.结果 经HBcAg刺激DC的CD86表达率为(92.14±5.12)%,明显高于HBsAg刺激组和未加抗原组(P<0.01);经HBcAg刺激组DC诱导同种异体静止T细胞增殖的能力每分钟液闪计数值(cpm)为34259±3127,明显高于HBsAg刺激组(20258±2917)和单个核细胞组(3469±417),P<0.01;经HBcAg刺激组DC MLR中IL-12浓度为(342±42.3)ng/L,分别高于HBsAg刺激组和未加抗原组(P<0.01).结论 体外经HBcAg刺激DC可有效提呈抗原病毒,并可进一步刺激T细胞产生.  相似文献   

3.
慢性乙型肝炎患者外周血树突状细胞功能的研究   总被引:23,自引:2,他引:21  
目的研究慢性乙型肝炎患者外周血树突状细胞(DC)的免疫功能.方法从慢性乙型肝炎患者外周血中分离单个核细胞,用无血清培养法分离培养DC,用流式细胞仪检测DC表型,用液闪计数仪观察DC对T细胞的增殖作用,用ELISA法检测混合淋巴细胞反应(MLR)中细胞因子的分泌水平.结果患者组DC的CD86的表达率为(70.2±5.2)%,明显低于正常人组(95.3±3.8)%,P<0.01;其诱导T细胞增殖能力每分钟液闪计数cpm为10000±2000,明显低于正常人组(cpm为30000±3000),P<0.01患者MLR中IL-12为(120.0±19.7)pg/ml,γ-干扰素为(799.0±161.3)pg/m1,明显低于正常人组的(280.0±41.1)pg/ml和(3359.0±635.4)pg/ml,P<0.01.结论慢性乙型肝炎患者外周血DC免疫功能低下,并与DC表面CD86的表达率下降及DC分泌IL-12减少密切相关.  相似文献   

4.
背景:近年研究显示慢性乙型肝炎(CHB)患者体内树突状细胞(DC)存在不同程度的功能缺失。胸腺肽α1(T-α1)是一种生物学应答调节物质,对CHB的临床治疗有较好疗效。目的:研究T-α1对CHB患者外周血DC分化和功能成熟的影响,寻求改善DC功能的途径。方法:从12例CHB患者和10名健康志愿者的外周血单个核细胞(PBMC)中分离培养DC。培养过程中应用不同浓度T-α1干预DC。以流式细胞仪检测DC表面标志,以甲基噻唑基四唑(MTT)实验检测混合淋巴细胞反应中DC刺激T细胞增殖的能力。结果:从PBMC分离培养得到的外周血DC呈现典型树突状形态。CHB组DC表面标记物CD80、CD86、人白细胞位点DR抗原(HLA-DR)水平以及刺激T细胞增殖的能力显著低于正常对照组(P〈0.001);经T-α1干预后,两组上述指标均较相应空白对照升高,尤以0.5μg/mlT-α1的作用为著(P〈0.05),可使CHB组上述指标恢复至正常水平。结论:T-α1能促进CHB患者外周血DC分化和功能成熟,在CHBDC疫苗的研究中可能具有重要价值。  相似文献   

5.
目的:研究补肾健脾解毒法中药复方对慢性HBV携带者树突状细胞(DC)的影响。方法:研究分为两个试验组。治疗组纳入30例慢性HBV携带者,对照组纳入10例健康志愿者,分别采用补肾健脾解毒法中药复方、安慰剂干预48周,观察两组人员治疗前后DC的成熟表面标志物、同种混合淋巴细胞反应(MLR)及其细胞因子(IL-12、IFN-γ)的变化。结果:基线时,治疗组患者的DC成熟表面标记物HLA(人白细胞抗原)-DR、CD86、CD80和CD1α的表达水平分别为61.34%、55.78%、42.63%、43.17%,明显低于对照组的90.52%、83.26%、76.81%、84.90%(P〈0.01);DC诱导MLR的能力、MLR上清液中IL-12和IFN-γ的表达水平全都明显低于对照组(P〈0.01)。治疗48周后,治疗组DC成熟表面标记物的表达水平均较治疗前明显上升(P〈0.01),但仍显著低于对照组(P〈0.01);治疗组患者对DC诱导MLR能力也有显著提升,MLR上清液中IL-12和IFN-γ的表达水平明显上升(P〈0.01),但DC诱导MLR能力及IFN-γ的表达水平未达到对照组水平(P〈0.05或0.01)。结论:补肾健脾解毒法中药复方能促进慢性HBV携带者的DC成熟并改善其免疫功能,从而产生有效的免疫应答以抑制/清除HBV。  相似文献   

6.
目的 :研究冠状动脉支架术后高敏C反应蛋白 (hsCRP)的升高与树突状细胞 (DC)的关系。方法 :术前及术后 2d分离 11例冠状动脉支架术患者外周血单个核细胞 (PBMC) ,在含粒细胞巨噬细胞集落刺激因子(GM CSF)和白细胞介素 4 (IL 4 )的培养条件下制备DC。用流式细胞仪检测DC表面共刺激分子CD86 (B7 2 )的表达 ;混合淋巴细胞反应 (MLR)检测DC对同种异体T淋巴细胞的刺激能力 ;ELISA法测定MLR上清液中的细胞因子 ;比浊法测定hsCRP浓度 ,并探讨CD86表达与hsCRP的相关性。结果 :与术前比较 ,术后 2dDC表面CD86的表达明显增高 ;对T淋巴细胞刺激的能力增强 ;经DC刺激的淋巴细胞分泌促炎细胞因子 (IL 1β、IL 6、TNF α)增多 ,抑炎细胞因子 (IL 10 )减少 ;同时血hsCRP升高 ,且CD86的表达与血hsCRP水平正相关。结论 :支架术后DC的功能被激活 ,由此启动的T淋巴细胞的增殖和炎性反应可能是术后hsCRP升高的原因  相似文献   

7.
树突状细胞诱导免疫效应细胞对BEL-7402的生长抑制   总被引:3,自引:0,他引:3  
目的:体内外观察多种细胞因子和(或)肿瘤相关抗原(tumor allogenic antigen,TAA)刺激的正常人树突状细胞(DC)诱导免疫效应细胞对BEL-7402的生长抑制。方法:体外分别用人GM-CSF、IL-4、TNFα、BEL-7402TAA和人IL-2刺激正常人DC和去DC的单个核细胞(免疫效应细胞),5-6d后混合培养DC和免疫效应细胞1-2d。体外实验时效应细胞分无DC刺激组(A0组)、细胞因子培养和DC刺激组(A1组)、细胞因子和TAA培养的DC刺激组(A2组)。体内实验时,裸鼠分为3组:预防组(Ⅱ),于接种BEL-7402前1-2d天给DC激活的免疫效应细胞;治疗组(Ⅲ),待全部裸鼠移植瘤长出时给DC激活的免疫效应细胞;组Ⅱ,Ⅲ于给予DC激活免疫效应细胞后再间断给予DC培养上清液3-6d。对照组(I)给等量的1640培养液。结果:多细胞因子体外可刺激DC发生扩增并高表达B7分子。体外实验中最大杀伤效率:A2组为81%,A1组为68.1%,A0组为3.5%。体内实验中:组I和组Ⅲ第12d时12例全部发生移植瘤;组Ⅱ观察30d时,6例有1例发生移植瘤,观察45d时,仍只有1例发生移植瘤,组I、Ⅱ相差有非常显著意义(P=0.00466);在给予DC激活的免疫效应细胞后的第45d处死所有裸鼠并称瘤体的重量,组I、Ⅱ、Ⅲ比较相差有非常显著意义(P<0.01),组Ⅱ的6只裸鼠仅1只产生移植瘤,瘤重为0.27g。结论:激活的DC在抗恶性肿瘤中有重要作用。  相似文献   

8.
树突状细胞(DC)在免疫反应过程中起重要作用,近来的研究表明DC不同程度参与了乙型肝炎的发病过程。体外多种细胞因子对DC具有诱导作用,并且促使其表面免疫有关分子的表达增强。最近有研究在体内观察了粒细胞巨噬细胞集落刺激因子对DC的诱导作用。体外研究表明干扰素(IFN)α诱导的DC在抗肿瘤免疫调节中可能发挥作用。IFNα在体内对DC的影响,特别是对DC表面免疫有关分子表达的调节作用研究尚少。CD1α是DC的重要标志,本研究旨在IFNα抗乙型肝炎病毒的同时,探讨IFNα在体内对DC的免疫调节作用,  相似文献   

9.
目的探讨肝癌患者外周血单个核细胞(PBMC)来源树突状细胞(DC)表面分子表达及负载肿瘤抗原前后免疫功能变化与免疫逃逸的关系。方法分离18例乙型肝炎相关原发性肝癌、11例乙型肝炎肝硬化患者和10名健康献血者PBMC,体外培养,并加入重组人粒细胞巨噬细胞集落刺激因子(GM-CSF)和白细胞介素-4(IL-4)诱导DC。以共聚焦显微镜和扫描电镜观察形态,以流式细胞仪检测DC表面人类白细胞抗原(HLA)-DR、CD1a、CD80、CD83、CD86等分子表达水平。以HCCLM6肝癌细胞株制备肿瘤抗原,分别负载3种DC,最后以混合淋巴细胞反应(MLR)测定DC负载前后刺激同种异型T淋巴细胞增殖能力,并测定MLR上清液中IL-12的含量。结果肝硬化和肝癌组PBMC、DC得率低于正常组(P<0.05);HLA- DR、CD1a、CD80和CD86等分子表达水平也低于正常组(P<0.05);负载肿瘤抗原前肝硬化和肝癌组刺激同种异型T淋巴细胞增殖能力和MLR上清液中IL-12含量明显低于正常组,负载肿瘤抗原后3组均提高, 并以肝硬化组提高最为明显,但IL-12含量仍低于正常组。结论DC表型和功能缺陷可能是乙型肝炎病毒产生免疫耐受和肝癌细胞免疫逃逸的重要机制。肝硬化患者DC仍有一定功能。  相似文献   

10.
雷帕霉素对人树突状细胞功能的影响   总被引:7,自引:0,他引:7  
目的 研究雷帕霉素 (RPM)对人树突状细胞 (DC)功能的影响。方法 分离外周血单个核细胞 (PBMC) ,在含粒细胞巨噬细胞集落刺激因子 (GM CSF)、白介素 4 (IL 4 )以及有或无RPM的培养条件下制备DC。用流式细胞仪检测DC表面共刺激分子CD86 (B7 2 )的表达 ;混合淋巴细胞反应(MLR)检测DC对同种异体T淋巴细胞的刺激能力 ;ELISA法测定MLR上清液中的细胞因子。结果 与对照组比较 ,经RPM处理的DC表面CD86的表达明显降低 ;对T淋巴细胞刺激的能力下降 ;MLR中致炎细胞因子 (IL 1β ,IL 6 ,TNF a)浓度降低。RPM的这些作用呈浓度依赖性。 结论 雷帕霉素对人树突状细胞功能有明显的抑制作用 ,可能是其防止支架术后再狭窄的机制之一  相似文献   

11.
Relying on a certain degree of abstraction, we can propose that no particular distinction exists between animate or living matter and inanimate matter. While focusing attention on some specifics, the dividing line between the two can be drawn. The most apparent distinction is in the level of structural and functional organization with the dissimilar streams of ‘energy flow’ between the observed entity and the surrounding environment. In essence, living matter is created from inanimate matter which is organized to contain internal intense energy processes and maintain lower intensity energy exchange processes with the environment. Taking internal and external energy processes into account, we contend in this paper that living matter can be referred to as matter of dissipative structure, with this structure assumed to be a common quality of all living creatures and living matter in general. Interruption of internal energy conversion processes and terminating the controlled energy exchange with the environment leads to degeneration of dissipative structure and reduction of the same to inanimate matter, (gas, liquid and/or solid inanimate substances), and ultimately what can be called ‘death.’ This concept of what we call dissipative nature can be extended from living organisms to social groups of animals, to mankind. An analogy based on the organization of matter provides a basis for a functional model of living entities. The models relies on the parallels among the three central structures of any cell (nucleus, cytoplasm and outer membrane) and the human body (central organs, body fluids along with the connective tissues, and external skin integument). This three-part structural organization may be observed almost universally in nature. It can be observed from the atomic structure to the planetary and intergalactic organizations. This similarity is corroborated by the membrane theory applied to living organisms. According to the energy nature of living matter and the proposed functional model, the decreased integrity of a human body's external envelope membrane is a first cause of the structural degradation and aging of the entire organism. The aging process than progresses externally to internally, as in single cell organisms, suggesting that much of the efforts towards the restoration and maintenance of the mechanisms responsible for structural development should be focused accordingly, on the membrane, i.e., the skin. Numerous reports indicate that all parts of the human body, like: bones, blood with blood vessels, muscles, skin, and so on, have some ability for restoration. Therefore, actual revival of not only aging tissue of the human body's membrane, but the entire human body enclosed within, with all internal organs, might be expected. We assess several aging theories within the context of our model and provide suggestions on how to activate the body's own anti-aging mechanisms and increase longevity. This paper presents some analogies and some distinctions that exist between the living dissipative structure matter and inanimate matter, discusses the aging process and proposes certain aging reversal solutions.  相似文献   

12.
The immunoneuroendocrine role of melatonin   总被引:19,自引:0,他引:19  
Abstract: A tight, physiological link between the pineal gland and the immune system is emerging from a series of experimental studies. This link might reflect the evolutionary connection between self-recognition and reproduction. Pinealectomy or other experimental methods which inhibit melatonin synthesis and secretion induce a state of immunodepression which is counteracted by melatonin. In general, melatonin seems to have an immunoenhancing effect that is particularly apparent in immunodepressive states. The negative effect of acute stress or immunosuppressive pharmacological treatments on various immune parameters are counteracted by melatonin. It seems important to note that one of the main targets of melatonin is the thymus, i.e., the central organ of the immune system. The clinical use of melatonin as an immunotherapeutic agent seems promising in primary and secondary immunodeficiencies as well as in cancer immunotherapy. The immunoenhancing action of melatonin seems to be mediated by T-helper cell-derived opioid peptides as well as by lymphokines and, perhaps, by pituitary hormones. Melatonin-induced-immuno-opioids (MHO) and lymphokines imply the presence of specific binding sites or melatonin receptors on cells of the immune system. On the other hand, lymphokines such as -γ-interferon and interleukin-2 as well as thymic hormones can modulate the synthesis of melatonin in the pineal gland. The pineal gland might thus be viewed as the crux of a sophisticated immunoneuroendocrine network which functions as an unconscious, diffuse sensory organ.  相似文献   

13.
Abstract: The effect of swimming at night on rat pineal melatonin synthesis was compared with that of light exposure at night. Rats were forced to swim at 0030 hr (lights out at 2000 hr) and sacrificed by decapitation 15 and 30 min later, immediately after swimming. Other groups of animals were exposed to white light (650μW/cm2) for 15 and 30 min at same time. Swimming caused a rapid and highly significant drop in the melatonin content in the pineal gland; however, the activity of N-acetyltransferase (NAT), the supposed rate limiting enzyme in the melatonin production, was not changed. Despite the drop in pineal melatonin levels, serum concentrations of the indole remained elevated in the rats that swam. In contrast, melatonin levels in the pineal and serum of light exposed rats fell precipitously, accompanied by a significant suppression of NAT activity. Since we anticipated that the strenuous exercise associated with swimming may induce release of artrial natriuretic peptide (ANP) from the heart, which in turn could cause the release of pineal melatonin, in a second study we injected physiological saline intravenously to stretch the cardiac muscle and release ANP. Three milliliters of normal saline was injected during the day into the jugular vein of anesthetized rats that were pretreated with isoproterenol to stimulate pineal melatonin production. Animals were killed 15 min after the saline injection, and pineal NAT activity and pineal melatonin levels were measured. The saline injections caused no alteration in the elevated levels of either NAT or melatonin. These data suggest that the disparity in pineal NAT activity (which was high) and pineal melatonin (which was low), in animals swum at night, may not be caused by ANP which is released during strenuous exercise such as swimming.  相似文献   

14.
15.
Abstract: Well-established circadian physiology supports the view that photoperiodic time measurement utilizes the coincidence between the presence of light and a photosensitive phase of a 'biological clock' to alter reproductive status—the so-called external coincidence model of seasonal breeding. In this review, we examine the mechanism whereby photoperiod interacts with presumed suprachiasmatic nuclei activity to allow endogenous melatonin to normally synchronize reproductive activity to the optimal time of year. The Romney Marsh sheep is particularly explored as an experimental model. It is suggested that the on/off activity of seasonal reproduction may be a robust mechanism able to be predictably manipulated by the judicious use of the light/dark cycle and exogenous melatonin, but firmly based on circadian principles.  相似文献   

16.
Abstract: Herein we documented the response of pineal melatonin production to electrolytes known to be effective on pineal function in view of a possible circadian stage dependence. We studied the release of melatonin by perifused rat pineal glands at 2 different circadian stages corresponding to the middle of the light and dark periods, i.e., respectively, 7 and 19 HALO (Hours After Light Onset, L:D = 12:12). The initial efflux rates were, as expected, much higher in the perifusates of glands removed from rats sacrificed during the dark phase than of those removed during the light phase. After 3 hr of perifusion, melatonin release reached similar levels which were found constant up to the 8th hr of perifusion, whatever the circadian stage. Perifusion of the glands with physiological concentrations for the rat of calcium (5.2 mmol/1) and magnesium (1.34 mmol/1) resulted in a stimulatory effect on the pineal glands removed from rats sacrificed in the middle of the dark period (19 HALO), whereas no effects were observed on the pineal glands removed from rats sacrificed during the light (7 HALO). Lithium (0.28 and 0.55 mmol/1) was ineffective on melatonin release in pineal glands removed 7 and 19 HALO. Our results show differences in the initial efflux rates of melatonin and in the response of perifused pineal glands to calcium and magnesium according to the circadian stage.  相似文献   

17.
Microbiology of human immunodeficiency virus anorectal disease   总被引:3,自引:3,他引:0  
PURPOSE: Individuals who are seropositive for the human immunodeficiency virus are at high risk for opportunistic infection and anorectal disorders. Little prospective information is available regarding anorectal pathogens in these patients. METHODS: One hundred sixty-three HIV-seropositive patients presented to the colorectal clinic between 1989 and 1992. Forty-seven (29 percent) patients were thought to have an infectious process and were prospectively studied using a standardized multiculture protocol. RESULTS: Mean age was 33 (range, 19–59) years. All were male; high-risk behavior accounted for 87 percent of HIV transmissions. Presenting complaints included anorectal pain (79 percent), pus per anum (28 percent), and blood per anum (26 percent). Examination revealed perianal tenderness (60 percent), condyloma (38 percent), perianal ulcers (38 percent), and anal fissures (34 percent). Sixty-six sets of cultures were performed; 28 patients had one set, 15 had two sets, and 4 had three sets. Thirty-two of these 47 patients (68 percent) had positive cultures including herpes (50 percent), cytomegalovirus (25 percent),Neisseria gonorrhoeae (16 percent), chlamydia (16 percent), acidfast bacilli (2 percent), and others (9 percent). Six of 32 patients with positive cultures had more than one organism cultured. Sixteen (50 percent) patients with positive cultures were treated medically, 8 (25 percent) were treated surgically and 8 (25 percent) were treated with both modalities. Sixty-one procedures were performed on 17 patients for condylomata. Eighteen patients had 20 procedures for abscesses, 50 percent of whom had positive cultures for other than common bowel flora; all improved. Fourteen patients underwent 33 procedures for perianal fistulas.Mycobacterium fortuitum was cultured from one patient who required 13 procedures for abscesses and fistulas. Forty-five (96 percent) patients were followed for an average of 12.5 months ±2.9 SEM (range, 1–94 months). Symptoms were improved or resolved in 22 of 32 (69 percent) patients with positive cultures and in 11 of 13 (84 percent) with negative cultures. CONCLUSIONS: Specific pathogens may often be identified in human immunodeficiency virus-seropositive patients with anorectal disorders if aggressively sought. Although patients without specific pathogens identified may be expected to improve with planned empiric treatment, positive identification allows more directed therapy.  相似文献   

18.
Duodenal diverticula are a relatively common condition. They are asymptomatic, unless they become complicated, with perforation being the rarest but most severe complication. Surgical treatment is the most frequently performed approach. We report the case of a patient with a perforated duodenal diverticulum, which was diagnosed early and treated conservatively with antibiotics and percutaneous drainage of secondary retroperitoneal abscesses. We suggest this method could be an acceptable option for the management of similar cases, provided that the patient is in good general condition and without septic signs.  相似文献   

19.
Abstract: The abundance of gap junctions between rat pineal astrocytes formed by connexin43 (Cx43) was studied during development. Levels and distribution of Cx43 were measured by immunoblotting and indirect immunofluorescence, respectively. The amount of Cx43 in cells located within the gland was low until about the 7th postnatal day and increased to adult values between the 14th and 21st days postpartum. Although astrocytes, recognized by their vimentin immunoreactivity, were scarce before birth, they were abundant by the 7th postnatal day suggesting that the low levels of Cx43 found at this age corresponded to a low expression of this protein. Localization of the immunoreactivity to Cx43 and vimentin showed a close correlation, indicating that mature or immature pineal astrocytes form gap junctions made of Cx43. Since Cx43 levels attained their adult values at about the time the innervation and the functional state of the gland reached maturity (2–3 weeks after birth), it is proposed that astrocyte gap junctions are involved in the function of the adult rat pineal gland.  相似文献   

20.
Postural orthostatic tachycardia syndrome (POTS) is a badly known pathology because its diagnosis is not based on the conventional methods of investigation. The orthostatic test allows to make the diagnosis easily. The objective of this study is to determine cardiovascular autonomic reflexes of 70 patients having POTS. The tests of exploration of the autonomic nervous system practised are: deep breathing, hand grip, mental stress and orthostatic test. The analysis of orthostatic test showed that the increase of the cardiac frequency, relative to the state of “β” peripheral sympathetic hyperactivity occurred before the 2nd minute in 80% of patients. The POTS was considered “florid” in 43% of patients and had complicated of a rough and severe fall of systolic blood pressure inferior to 70 mmHg in four patients, after the fifth minute of the test. The analysis of the different tests had shown vagale hyperactivity in 63% of patients on deep breathing, in 93% of patients on hand grip and in 100% on orthostatic test. The “α” central sympathetic activity was increased in 76% of the cases and “β” central sympathetic activity was high in 83% of cases. The “α” peripheral hyperactivity was observed in 63% of patients on hand grip, and in 44% on orthostatic test. The analysis of cardiovascular autonomic reflexes on patients affected by POTS allowing the determination of their autonomic profile, will contribute probably to a better understanding of this pathology and to a better orientation of its care.  相似文献   

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