共查询到20条相似文献,搜索用时 15 毫秒
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《Critical reviews in biochemistry and molecular biology》2013,48(5):361-404
AbstractFor more than a century amyloid was considered to be an interesting, unique, but inconsequential pathologic entity that rarely caused significant clinical problems. We now recognize that amyloid is not one entity. In vivo it is a uniform organization of a disease, or process, specific protein co-deposited with a set of common structural components. Amyloid has been implicated in the pathogenesis of diseases affecting millions of patients. These range from Alzheimer's disease, adult-onset diabetes, consequences of prolonged renal dialysis, to the historically recognized systemic forms associated with inflammation and plasma cell disturbances. Strong evidence is emerging that even when deposited in local organ sites significant physiologic effects may ensue.With emphasis on Aβ amyloid, we review the present definition, classification, and general in vivo pathogenetic events believed to be involved in the deposition of amyloids. This encompasses the need for an adequate amyloid precursor protein pool, whether precursor proteolysis is required prior to deposition, amyloidogenic amino acid sequences, fibrillogenic nucleating particles, and an in vivo microenvironment conducive to fibrillogenesis. The latter includes several components that seem to be part of all amyloids. The role these common components may play in amyloid accumulation, why amyloids tend to be associated with basement membranes, and how one may use these findings for anti-amyloid therapeutic strategies is also examined. 相似文献
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眼镜蛇血浆T3,T4,TsH浓度的年周期变化律 总被引:1,自引:1,他引:0
本文报道眼镜蛇Naja naja Atra甲状腺功能的年周期律。结果表明:1.眼镜蛇血浆T3、T4和TsH的浓度均呈单峰曲线的年周期变化。血浆TsH的浓度及血浆T3、T4浓度的高峰时间分别是4月16日及7月2日和7月8日。血浆TsH的高峰时间比血浆T3、T4浓度的高峰时间提前2个多月。2.眼镜蛇T3、T4分泌增多的内因是蛇自身节律性的调节。3.眼镜蛇的TsH是甲状腺结构变化的促成者。 相似文献
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Alves Dde S Moraes AS Nitz N de Oliveira MG Hecht MM Gurgel-Gonçalves R Cuba CA 《Experimental parasitology》2012,131(2):239-244
Species of Acanthamoeba can cause keratitis and brain infections. The characterization of environmental isolates is necessary to analyze the risk of human infection. We aimed at identifying and genotyping Acanthamoeba isolates from soil, swimming pools, and water features in Brasília, Federal District, Brazil, as well as determining their physiological characteristics and pathogenic potential. Among the 18 isolates studied, eight were similar to genotype T5, five to T4, and one to T2/T6, classified by the sequence analysis of 18S rDNA. Genotypes of four isolates were not determined. Ten isolates (55%) grew at 37 °C and seven (39%) grew in media with 1.5M mannitol, which are the physiological parameters associated with pathogenic Acanthamoeba; also, four isolates from swimming pools presented high pathogenic potential. Our results indicate a widespread distribution of potentially pathogenic Acanthamoeba T4, T5, and T2/T6 in different environmental sources in Brasília, revealing the potential risk of human infection and the need of preventive measures. 相似文献
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Castella B Riganti C Fiore F Pantaleoni F Canepari ME Peola S Foglietta M Palumbo A Bosia A Coscia M Boccadoro M Massaia M 《Journal of immunology (Baltimore, Md. : 1950)》2011,187(4):1578-1590
Vγ9Vδ2 T cells play a major role as effector cells of innate immune responses against microbes, stressed cells, and tumor cells. They constitute <5% of PBLs but can be expanded by zoledronic acid (ZA)-treated monocytes or dendritic cells (DC). Much less is known about their ability to act as cellular adjuvants bridging innate and adaptive immunity, especially in patients with cancer. We have addressed this issue in multiple myeloma (MM), a prototypic disease with several immune dysfunctions that also affect γδ T cells and DC. ZA-treated MM DC were highly effective in activating autologous γδ T cells, even in patients refractory to stimulation with ZA-treated monocytes. ZA inhibited the mevalonate pathway of MM DC and induced the intracellular accumulation and release into the supernatant of isopentenyl pyrophosphate, a selective γδ T cell activator, in sufficient amounts to induce the proliferation of γδ T cells. Immune responses against the tumor-associated Ag survivin (SRV) by MHC-restricted, SRV-specific CD8(+) αβ T cells were amplified by the concurrent activation of γδ T cells driven by autologous DC copulsed with ZA and SRV-derived peptides. Ancillary to the isopentenyl pyrophosphate-induced γδ T cell proliferation was the mevalonate-independent ZA ability to directly antagonize regulatory T cells and downregulate PD-L2 expression on the DC cell surface. In conclusion, ZA has multiple immune modulatory activities that allow MM DC to effectively handle the concurrent activation of γδ T cells and MHC-restricted CD8(+) αβ antitumor effector T cells. 相似文献
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Noest AJ 《Journal of theoretical biology》2000,207(2):195-216
One basic task of immune systems is to detect signals from unknown "intruders" amidst a noisy background of harmless signals. To clarify the functional importance of many observed lymphocyte properties, I ask: What properties would a cell have if one designed it according to the theory of optimal detection, with minimal regard for biological constraints? Sparse and reasonable assumptions about the statistics of available signals prove sufficient for deriving many features of the optimal functional structure, in an incremental and modular design. The use of one common formalism guarantees that all parts of the design collaborate to solve the detection task. Detection performance is computed at several stages of the design. Comparison between design variants reveals e.g. the importance of controlling the signal integration time. This predicts that an appropriate control mechanism should exist. Comparing the design to reality, I find a striking similarity with many features of T cells. For example, the formalism dictates clonal specificity, serial receptor triggering, (grades of) anergy, negative and positive selection, co-stimulation, high-zone tolerance, and clonal production of cytokines. Serious mismatches should be found if T cells were hindered by mechanistic constraints or vestiges of their (co-)evolutionary history, but I have not found clear examples. By contrast, fundamental mismatches abound when comparing the design to immune systems of e.g. invertebrates. The wide-ranging differences seem to hinge on the (in)ability to generate a large diversity of receptors. 相似文献
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《Current opinion in plant biology》2000,3(3):169
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《生物产业技术》2017,(5)
T细胞受体工程T细胞疗法(TCR-T)是肿瘤治疗中很有希望的一种特异性过继性细胞免疫疗法,该方法主要是将肿瘤抗原特异的TCR基因通过载体转入自体的淋巴细胞中,再回输至病人体内以达到杀伤肿瘤细胞的目的。目前对TCR-T的挑战是肿瘤抗原特异的高亲和性的TCR基因的获取和高度表达以及TCR双链α和β的正确配对。除此之外,通过临床试验已经发现,由于TCR的高反应性,TCR-T会在靶向肿瘤细胞表面抗原的同时作用于正常组织而产生强的脱靶效应,因此,选择合适的靶抗原也是TCR-T细胞治疗能够发挥其优越效果的关键因素。对TCR基因的表达和调节机制、TCR配对的优化战略等TCR-T在肿瘤治疗中面临的挑战,以及TCR-T的临床转化和应用价值进行了探讨。 相似文献
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The molecular mechanisms that regulate mature T cell fate and enable cells to differentiate into memory T cells are largely unknown. Memory T cells share certain key features with stem cells: they both have the ability to self-renew and are long-lived. The Wnt-β-catenin signaling pathway is a key player in regulating stem cell self-renewal and differentiation. We generated a conditional knockout mouse that specifically lacks β-catenin in mature T cells and report in this article that β-catenin is not involved in regulating effector versus memory T cell differentiation. β-catenin-deficient memory T cells were phenotypically and functionally indistinguishable from control cells and made normal recall responses. β-catenin deficiency does not affect T cell migration, T cell function in a model of chronic infection, or lymphopenia-induced proliferation. Together, our data suggest that self-renewal and differentiation are regulated differently in memory T cells compared with epithelial and hematopoietic stem cells. 相似文献
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There is substantial need for molecularly defined tumor antigens to prime cytotoxic T cells in vivo for cancer immunotherapy, especially in the case of tumor entities for which only a few tumor antigens have been defined so far. In this review, we present the Tübingen approach to identify, select, and validate large numbers of MHC/HLA class I–associated peptides derived from tumor-associated antigens. Step 1 is the identification of naturally presented HLA-associated peptides directly from primary tumor cells. Step 2 is selection of tumor-associated peptides from step 1 by differential gene expression analysis and data mining. Step 3 is validation of selected candidates by monitoring in vivo T-cell responses in the context of patient-individualized immunizations. Our approach combines methods from genomics, proteomics, bioinformatics, and T-cell immunology. The aim is to develop effective immunotherapeutics consisting of multiple tumor-associated epitopes in order to induce a broad and specific immune response against cancer cells.This work was presented at the first Cancer Immunology and Immunotherapy Summer School, 8–13 September 2003, Ionian Village, Bartholomeio, Peloponnese, Greece. 相似文献