Review series on helminths,immune modulation and the hygiene hypothesis: The broader implications of the hygiene hypothesis

Man has moved rapidly from the hunter–gatherer environment to the living conditions of the rich industrialized countries. The hygiene hypothesis suggests that the resulting changed and reduced pattern of exposure to microorganisms has led to disordered regulation of the immune system, and hence to increases in certain inflammatory disorders. The concept began with the allergic disorders, but there are now good reasons for extending it to autoimmunity, inflammatory bowel disease, neuroinflammatory disorders, atherosclerosis, depression associated with raised inflammatory cytokines, and some cancers. This review discusses these possibilities in the context of Darwinian medicine, which uses knowledge of evolution to cast light on human diseases. The Darwinian approach enables one to correctly identify some of the organisms that are important for the ‘Hygiene’ or ‘Old Friends’ hypothesis, and to point to the potential exploitation of these organisms or their components in novel types of prophylaxis with applications in several branches of medicine.     

硅藻多不饱和脂肪酸免疫调节作用的研究

<正>硅藻是一类单细胞藻类,能够产生大量的油脂成分,许多硅藻种类含有大量的二十碳五烯酸(EPA),如:在Nitzschia alba和Nitzschia laevis这两个品系中较高[1]。后者的油脂含量高达干重的40%,其中的脂肪酸主要为C14:0、C16:0、C16:1、C20:4和C20:5,还含有少量的     

玉屏风散治疗实验性小鼠单纯疱疹病毒性角膜炎的观察

目的观察玉屏风散对实验性小鼠单纯疱疹病毒角膜炎（HSK）的治疗效果,探讨其对机体免疫功能的调节作用。方法将90只小鼠随机分为实验组、模型对照组及空白组各30只。通过单纯疱疹病毒1型（HSV-1）感染60只小鼠60眼（实验组、模型对照组各30只）的角膜建立HSK小鼠,实验组小鼠灌服玉屏风散水煎剂,模型对照组和空白组灌服等量的生理盐水,每日一次在裂隙灯下角膜荧光素染色检查小鼠角膜上皮炎的愈合情况及角膜的混浊度;并分别在给药后第7天、第14天及第28天随机取3组小鼠眼眶静脉血,离心取血清,ELISA法测定小鼠血清白细胞介素-2（IL-2）的水平,同时行眼球组织病理学检查。结果实验组小鼠角膜混浊度明显低于模型对照组;实验组小鼠单纯疱疹病毒角膜炎治愈率75%,对照组治愈率30%,两组比较差异有显著性（P〈0.05）;实验组小鼠第14天、第28天血清IL-2含量高于模型对照组及空白组,差异有显著性（P〈0.05）;小鼠角膜组织病理检查示实验组第7天、第14天、第28天角膜炎症反应程度较模型对照组轻。结论玉屏风散能调节小鼠免疫功能,对单纯疱疹病毒角膜炎有明显疗效。     

五灵胶囊对正常及免疫性肝损伤小鼠IL-2、IL-6的影响

目的:探讨五灵胶囊对正常小鼠及免疫性肝损伤小鼠体内白细胞介素2（IL-2）、白细胞介素6（IL-6）活性的影响。方法:BALB/C系小鼠经脂多糖（LPS）处理和未经LPS处理,灌胃12d后,取脾脏体外培养48h、72h,收集脾细胞培养上清作用于靶细胞,分别用MTT法测定IL-2活性,用放免法测定IL-6活性。结果:五灵胶囊有促进小鼠Th细胞分泌IL-2的作用,使肝损伤所致低水平的IL-2明显升高,对损伤或正常小鼠IL-6水平无影响。结论:五灵胶囊促进IL-2分泌,调节免疫作用。     

Effects of Cimetidine on IL－2 and T Suppressor Cell Function in Rats with Obstructive Jaundice

ＥｆｆｅｃｔｓｏｆＣｉｍｅｔｉｄｉｎｅｏｎＩＬ－２ａｎｄＴＳｕｐｐｒｅｓｓｏｒＣｅｌｌＦｕｎｃｔｉｏｎｉｎＲａｔｓｗｉｔｈＯｂｓｔｒｕｃｔｉｖｅＪａｕｎｄｉｃｅＤＩＮＧＸｉａｎ－ｚｈｏｎｇ（丁显仲）；ＬＩＨｕａ（李桦）；ＸＩＯＮＧＳｈｕ－ｔａｏ（熊叔...     

白芍总甙、芍药甙和白芍总甙去除芍药甙对佐剂性关节炎大鼠的免疫调节作用

福氏完全佐剂致炎后ｄ１８，佐剂性关节炎（ＡＡ）大鼠刀豆素Ａ（３ｍｇ·Ｌ－１）诱导的脾淋巴细胞增殖反应显著低于正常对照水平，脂多糖（６ｍｇ·Ｌ－１）诱导的大鼠腹腔巨噬细胞（ＰＭΦｓ）产生ＩＬ－１显著高于正常对照大鼠。０．５～３１２．５ｍｇ·Ｌ－１白芍总甙（ＴＧＰ）、芍药甙（ＰＦ）和白芍总甙去除芍药甙（ＴＧＰ－ＰＦ）均能浓度依赖性地增强ＡＡ大鼠低下的脾淋巴细胞增殖反应（量效曲线均呈钟罩形），降低ＡＡ大鼠ＰＭΦｓ过度产生ＩＬ－１（量效曲线均呈倒钟罩形）。其中，２．５～６２．５ｍｇ·Ｌ－１ＴＧＰ的调节作用显著强于ＰＦ和ＴＧＰ－ＰＦ各等剂量组。这些结果表明，上述三种药物均具有浓度和机能依赖性的双向免疫调节作用，ＴＧＰ的作用最强。     

Immunoregulatory abnormalities in myelodysplastic disorders

Immunoregulation was assessed in a group of patients with myelodysplasia (MDS) by flow cytometric analysis of peripheral blood lymphocyte subsets and in vitro studies of mitogen-stimulated T-lymphocyte blastogenesis. Mitogenesis was significantly depressed in MDS patients compared to controls (p less than .001) and a similar defect was found in a small group of patients with untreated acute nonlymphocytic leukemia (ANLL) (p less than .005). The impaired mitogenic response ability of T-cells in these patients did not appear to be the result of alteration in lymphocyte subpopulation ratios. The observed defect might result from defective cooperation between T-lymphocytes and abnormal myeloid elements. Alternatively, the lymphocytes themselves could be derived from the abnormal clone and thus be functionally abnormal.     

Anti-Idiotypic Regulatory Responses Induced by Vaccination with DNA Encoding Murine TCR Vα5 and Vβ2

There is evidence suggesting that anti-idiotypic regulation against T cells plays a role in maintaining homeostasis in the immune system, although its mechanism is not fully understood. By using DNA constructs encoding the TCR Vα5.2 and Vβ2.1 chains derived from ：in ovalbumin （OVA）-specific T cdl clone （OVA-T）, we herein demonstrated that vaccination with TCR-DNA effectively induced anti-idiotypic cellular as well as humoral responses. Serum samples from the TCR-DNA-vaccinated BALB/c mice were able to stain T cells in an idiotype-specific manner. CD4^＋ T cells from the TCR-DNA-vaccinated mice proliferated in response to stimulation with irradiated syngeneic OVA-T calls and secreted interferon-y but very little IL-4. Splenocytes from the TCR-DNA-vaccinated mice showed strong idiotype-specific CTL activity against the OVA-T cdls. Furthermore, adoptive transfer of the CD4^＋ or CD8^＋ T cells from the TCR-DNA-vaccinated mice resulted in hyporesponsiveness of syngeneic recipients. These results demonstrated that vaccination with DNA encoding TCR can effectively activate anti-idiotypic regulatory responses in vivo and thus providing a useful way for immunological intervention.     

Thymus leukemia antigen controls intraepithelial lymphocyte function and inflammatory bowel disease

Intestinal intraepithelial lymphocytes (IEL) bear a partially activated phenotype that permits them to rapidly respond to antigenic insults. However, this phenotype also implies that IEL must be highly controlled to prevent misdirected immune reactions. It has been suggested that IEL are regulated through the interaction of the CD8αα homodimer with the thymus leukemia (TL) antigen expressed by intestinal epithelial cells. We have generated and characterized mice genetically-deficient in TL expression. Our findings show that TL expression has a critical role in maintaining IEL effector functions. Also, TL deficiency accelerated colitis in a genetic model of inflammatory bowel disease. These findings reveal an important regulatory role of TL in controlling IEL function and intestinal inflammation.     

Modulation of CD1d-restricted NKT cell responses by using N-acyl variants of alpha-galactosylceramides

A form of alpha-galactosylceramide, KRN7000, activates CD1d-restricted Valpha14-invariant (Valpha14i) natural killer (NK) T cells and initiates multiple downstream immune reactions. We report that substituting the C26:0 N-acyl chain of KRN7000 with shorter, unsaturated fatty acids modifies the outcome of Valpha14i NKT cell activation. One analogue containing a diunsaturated C20 fatty acid (C20:2) potently induced a T helper type 2-biased cytokine response, with diminished IFN-gamma production and reduced Valpha14i NKT cell expansion. C20:2 also exhibited less stringent requirements for loading onto CD1d than KRN7000, suggesting a mechanism for the immunomodulatory properties of this lipid. The differential cellular response elicited by this class of Valpha14i NKT cell agonists may prove to be useful in immunotherapeutic applications.