Immune reactivity towards insulin, its amyloid and protein S100B in blood sera of Parkinson's disease patients

Peripheral immune responses can be sensitive indicators of disease pathology. We evaluated the autoimmune reactions to endocrine (insulin) and astrocytical (S100B) biomarkers in the blood sera of 26 Parkinson's disease (PD) patients compared with controls by using ELISA. We found a statistically significant increase of the autoimmune responses to both antigens in PD patients compared with controls with a mean increase of 70% and 50% in the autoimmune reactions towards insulin and S100B, respectively. Heterogeneity of the immune responses observed in patients may reflect the modulating effect of multiple variables associated with neurodegeneration and also changes in the basic mechanisms of individual autoimmune reactivity. We did not detect any pronounced immune reactions towards insulin amyloid fibrils and oligomers in PD patients, indicating that an amyloid-specific conformational epitope is not involved in immune recognition of this amyloid type, while sequential epitope of native insulin is hidden within the amyloid structures. Immune reactions towards S100B and insulin may reflect the neurodegenerative brain damaging processes and impaired insulin homeostasis occurring in PD.     

Natural killer cell activity and autologous mixed lymphocyte response of splenic,mesenteric lymph node,and colonic lymphocytes during DMH-induced colon carcinogenesis in the rat

Twoin vitro models of immune surveillance were used to examine the immune status of the gut-associated lymphoid tissue, mesenteric lymph nodes, and spleen during the early stages of 1,2-dimethylhydrazine (DMN)-induced colon tumorigenesis. DMH-and vehicletreated Fischer rats were sacrificed at one of three time points; one week, two months, or five months after cessation of treatment. Colonic, lymph node, and splenic natural killer cell cytolytic activity toward YAC-1 tumor targets and T-cell response to autologous la-induced balstogenesis were measured at each time point. We found little change in natural killer cell activity or T-cell proliferation induced by autologous Ia gene products at these time periods.This investigation was supported in part by grant CA26917 from the National Cancer Institute, Department of Health and Human Services.     

甘肃棘豆生物碱部位体内抗肿瘤作用及对免疫功能的影响

目的 研究甘肃棘豆生物碱部位对KM小鼠肝癌H22细胞抑制作用及其对KM小鼠免疫功能的影响。 方法 采用鼠源性肝癌细胞H22移植瘤法,将60只KM小鼠随机分为5组，其中高、中、低剂量组分别给予甘肃棘豆生物碱部位32、16、8 mg/kg体重灌胃，阴性对照组给予生理盐水（NS）20 mL/kg灌胃，5- 氟脲嘧啶（5-FU）组给予5-FU 15 mg/kg体重腹腔注射，每天1次，连续给药10天。检测平均瘤重和抑瘤率,计算脾指数、胸腺指数，MTT法测脾细胞增殖率。 结果 甘肃棘豆生物碱部位高、中、低剂量组对肝癌细胞H22实体移植瘤的抑制率分别为43%、29%、23%；各剂量组小鼠的脾指数和胸腺指数均明显高于阴性对照组，中、高剂量组明显高于5-FU 组（P＜0.05）；各剂量组在24、48、72 h的脾细胞增殖率也明显高于阴性对照组及5-FU 组（P＜0.01）。 结论 甘肃棘豆生物碱部位对KM小鼠肝癌H22移植瘤有抑制作用，并能增强KM小鼠免疫功能。     

Mathematical modelling of the spatio-temporal response of cytotoxic T-lymphocytes to a solid tumour.

In this paper a mathematical model describing the growth of a solid tumour in the presence of an immune system response is presented. In particular, attention is focused upon the attack of tumour cells by so-called tumour-infiltrating cytotoxic lymphocytes (TICLs), in a small, multicellular tumour, without necrosis and at some stage prior to (tumour-induced) angiogenesis. At this stage the immune cells and the tumour cells are considered to be in a state of dynamic equilibrium--cancer dormancy--a phenomenon which has been observed in primary tumours, micrometastases and residual disease after ablation of the primary tumour. Nonetheless, the precise biochemical and cellular mechanisms by which TICLs control cancer dormancy are still poorly understood from a biological and immunological point of view. Therefore we focus on the analysis of the spatio-temporal dynamics of tumour cells, immune cells and chemokines in an immunogenic tumour. The lymphocytes are assumed to migrate into the growing solid tumour and interact with the tumour cells in such a way that lymphocyte-tumour cell complexes are formed. These complexes result in either the death of the tumour cells (the normal situation) or the inactivation (sometimes even the death) of the lymphocytes. The migration of the TICLs is determined by a combination of random motility and chemotaxis in response to the presence of chemokines. The resulting system of four nonlinear partial differential equations (TICLs, tumour cells, complexes and chemokines) is analysed and numerical simulations are presented. We consider two different tumour geometries--multi-layered cell growth and multi-cellular spheroid growth. The numerical simulations demonstrate the existence of cell distributions that are quasi-stationary in time and heterogeneous in space. A linear stability analysis of the underlying (spatially homogeneous) ordinary differential equation (ODE) kinetics coupled with a numerical investigation of the ODE system reveals the existence of a stable limit cycle. This is verified further when a subsequent bifurcation analysis is undertaken using a numerical continuation package. These results then explain the complex heterogeneous spatio-temporal dynamics observed in the partial differential equation (PDE) system. Our approach may lead to a deeper understanding of the phenomenon of cancer dormancy and may be helpful in the future development of more effective anti-cancer vaccines.     

Characteristics of antibody responses in tick-borne encephalitis vaccination breakthroughs

Tick-borne encephalitis (TBE) virus is an important human pathogenic flavivirus that is endemic in Europe and Asia. The disease can be effectively prevented by inactivated vaccines and vaccination breakthroughs (VBTs) are rare. We investigated the characteristics of antibody responses in such VBTs in comparison to those in unvaccinated TBE patients. In contrast to the unvaccinated controls, most of the VBTs displayed a delayed IgM antibody response and had high avidity and strongly neutralizing antibodies already in the first sample taken upon hospitalization. The antibody profile of these patients therefore had the characteristics of an anamnestic immune response. In the VBTs analyzed, immunological priming and memory were apparently not sufficient or fast enough to prevent the disease.     

IL-4与IL-10联合诱导异种骨移植免疫耐受的体外研究

目的　探讨 IL - 4和 IL - 10在诱导异种骨移植免疫耐受中的作用。方法　反应细胞为 BAL B/c小鼠脾淋巴细胞 ,刺激细胞为新西兰白兔血淋巴细胞 ,刺激抗原为兔骨上清液。采用经典的混合淋巴细胞培养法及骨上清液与淋巴细胞混合培养法作为异种骨移植的体外实验模型。在各培养液中分别加入 IL - 4、IL - 10及两者联合应用 ,通过测定其 3H- Td R掺入率 ,观察不同细胞因子对刺激淋巴细胞增殖的影响。结果　无论在细胞刺激组还是骨上清液刺激组 ,IL- 4对淋巴细胞增殖均有显著抑制作用 (P<0 .0 0 1和 P<0 .0 5 ) ,IL- 10未表现出抑制作用 (P>0 .0 5 )。在两组 IL- 4和 IL - 10联合应用均产生比 IL - 4单独应用更为明显的细胞增殖抑制作用 (P<0 .0 0 1和 P<0 .0 5 )。结论　 IL - 4对由细胞或骨上清液刺激产生的淋巴细胞增殖均有很好的抑制作用 ,IL- 10没有表现出抑制作用 ;IL- 4与 IL- 10联合应用有协同抑制作用。     

17β-雌二醇对子宫内膜异位症患者在位子宫内膜间质细胞β-catenin mRNA和蛋白表达的影响

目的研究17β-雌二醇(17β-E2)对子宫内膜异位症(内异症)患者在位子宫内膜间质细胞β-catenin mRNA和蛋白表达的影响,探讨Wnt/β-catenin信号通路在介导雌激素促进内异症发生发展的作用。方法体外分离培养内异症患者在位子宫内膜间质细胞。用不同浓度17β-E2处理子宫内膜间质细胞48 h;此后选用10-10mol/L 17β-E2处理子宫内膜间质细胞12、24和48 h,逆转录聚合酶链反应(RT-PCR)和免疫印迹法(Western blotting)检测17β-E2处理前后子宫内膜间质细胞β-catenin mRNA和蛋白的表达水平。同法分析雌激素受体拮抗剂ICI182,780(10-6mol/L)对17β-E2促进β-catenin mRNA和蛋白表达的影响。免疫组织化学染色观察17β-E2作用后β-catenin在子宫内膜间质细胞中的定位。结果17β-E2能明显促进内异症患者在位子宫内膜间质细胞β-catenin mRNA和蛋白的表达,并呈剂量和时间依赖性,于10-10mol/L作用48 h最明显。雌激素受体拮抗剂ICI182,780能明显抑制17β-E2对子宫内膜间质细胞β-catenin mRNA和蛋白的表达。免疫组织化学染色发现17β-E2能促进β-catenin在子宫内膜间质细胞核内的表达。结论雌激素可能通过激活Wnt/β-catenin信号通路促进内异症在位子宫内膜的异位种植。     

The interactive role of mucosal T lymphocytes in intestinal growth, development and enteropathy

Abstract Over the past 15–20 years, research has progressively focused on the mucosal T cell as the central factor in the initiation of physiological or pathological changes, first in the growth and maturation of the early (postnatal) intestine, and second in adult-type enteropathies resulting from sensitivity to either food or pathogen-derived antigens. T cell-mediated events may be measured, for example, in terms of specific immunopathologic patterns of change and injury, such as type 1 (lymphocyte infiltration), type 2 (crypt hyperplasia) and type 3 (flat-destructive), which can be recognized and quantitated microscopically; by determination of lymphocyte reactivity through secretion of interleukin-2 receptors (IL-2R) into plasma or expression by mucosal lymphocytes; by quantitation of lymphocyte subsets emigrating into inflamed tissues by immunoperoxidase-labelled monoclonal antibodies; or by the determination of T cell receptor polymorphisms. Alterations in intestinal growth, structure and function at weaning are likely to be T cell-mediated as they are analogous to the same type 1/2 lesions that reflect modulation of adult mucosal architecture in food and parasite-induced hypersensitivity reactions. Enteropathies associated with HIV infection and T cell deficiency display a milder degree of villous flattening and impaired crypt hyperplasia than that typical of gluten-sensitivity, suggesting a reversion to lesser degrees of mucosal pathology (type 1/2). Clearly more information will accrue; meanwhile the remarks in this brief survey should provide a firm basis whereby clinician and scientist can meet, and together recognize and further dissect the modulatory effect of T lymphocytes on mucosal structure and function.     

肺癌患者红细胞免疫功能和T淋巴细胞亚群的检测及临床意义

作者对62例肺癌患者进行红细胞免疫功能及T淋巴细胞亚群测定，并与20例正常人对照。结果显示：肺癌组红细胞膜C3b受体活性（RBC－C3bRR）、CD3 、CD4 、CD4 ／CD8 比值均低于正常人（P＜0．05～0．01），红细胞膜的吸附免疫复合物（RBC－ICR）、CD8 均高于正常人（P＜0．05～0．01），因此认为红细胞免疫及T淋巴细胞亚群测定对肺癌的诊断、治疗及病情预后估计有一定价值。     

肺结核病人红细胞免疫功能及T淋巴细胞亚群的变化

①目的探讨红细胞免疫功能及Ｔ淋巴细胞亚群变化与肺结核的关系。②方法对４４例肺结核病人和４４例健康人的红细胞免疫功能、血清循环免疫复合物、Ｔ淋巴细胞亚群、ＮＫ细胞水平的变化进行了检测，并与对照组比较。③结果肺结核病人红细胞Ｃ３ｂ受体花环率（Ｅ－Ｃ３ｂＲＲ），ＣＤ４，ＣＤ４／ＣＤ８，ＮＫ细胞水平明显降低，ＣＤ８水平明显升高，与对照组相比，差异均有极显著意义（ｔ＝９．７６～２２．２４，Ｐ均＜０．０１）；复治组较初治组变化更明显（ｔ＝４．２７～１５．３２，Ｐ均＜０．０１）。Ｅ－Ｃ３ｂＲＲ与ＣＤ４，ＣＤ４／ＣＤ８，ＮＫ细胞水平呈正相关（ｒ＝０．２６９２～０．５４７９，Ｐ＜０．０５，０．０１），与ＣＤ８呈显著负相关（ｒ＝－０．３７４，Ｐ＜０．０１）。④结论红细胞免疫功能、Ｔ淋巴细胞亚群及ＮＫ细胞的异常与肺结核的发病及病情变化有一定关系。