肠-肾轴在新月体肾炎发病机制中的研究进展

新月体肾炎(CreGN)是最凶险的肾小球肾炎,常常导致终末期肾病.免疫机制是其发病和决定预后最重要的因素.近年来,肠道和肠道菌群在包括CreGN在内的多种肾脏病中作用受到关注,其中"肠-肾轴"通过肠道菌群、肠源性免疫细胞等途径会直接影响全身和肾脏免疫应答及相关病理生理机制.     

溃疡性结肠炎发病机制中免疫因素的研究进展

溃疡性结肠炎是一种常见的慢性肠道疾病,近年来发病呈上升趋势,而其发病机制目前尚不明确.目前认为与多种因素有关.环境因素作用于遗传易感者,在肠道菌丛的参与下,启动肠道免疫和非免疫系统,发生免疫反应和炎症,从而出现临床症状.其中免疫异常被认为是溃疡性结肠炎发病的重要因素,主要包括自身抗体、细胞免疫、细胞因子、环氧合酶与基质金属蛋白酶、氧自由基和一氧化氮等.本文综述了溃疡性结肠炎免疫发病机制中的各种影响因素.     

TGFβ1基因-509C/T多态性与IgA肾病免疫病理学的关联分析

IgA肾病为免疫介导炎症性慢性肾脏疾病，其遗传学机制仍不清楚。TGFβ1基因-509C／T单核苷酸多态性位于基因上游转录起始点前509by（NCBI SNP数据库：rs1800469），处于-731by至-453by间，而此区域恰是TGFβ1基因的负性调控区。我们曾报道，TGFβ1基因-509C／T可能不是我国汉族IgA肾病的遗传易感因子，但TGFβ1基因-509C／T与IgA肾病的血清球蛋白水平及肾免疫病理沉积有无关联，目前研究报道甚少。为此，本文初步探讨TGFβ1基因在IgA肾病免疫病理学中的遗传意义。     

调节性B细胞与肿瘤免疫逃逸

近年来，调节性B细胞（Breg）在肿瘤免疫研究中备受瞩目，多种实体肿瘤中均发现其大量浸润，直接或间接影响抗肿瘤免疫功能，发挥免疫调节效应。然而肿瘤浸润Breg的表型特征及其复杂的功能和机制尚有待系统解析。在此，基于现有研究成果，本文对肿瘤浸润Breg的表型、作用模式、驱动因素及临床相关性进行论述。     

免疫相关性妊娠丢失研究进展

妊娠丢失是指在孕20周以前或胎儿体重〈490g、或不能获得有生机儿前的流产或死胎。其病因除与遗传、解剖、内分泌因素有关外，约有40％～65％与免疫因素有关，其中包括自身免疫、同种免疫、母儿血型不和以及子宫阴道免疫导致的妊娠丢失。下面就不同因素所致妊娠丢失的机制及治疗进展综述如下。     

肺脏的区域免疫特性及其在感染性疾病中的调控机制研究进展

肺脏是与外界环境相通的开放系统，除了肩负气体交换的生理功能外，也是众多经空气传播的病原微生物等外界抗原的主要靶器官，在防御并清除病原微生物感染过程中发挥重要调控作用。因此，肺脏兼具免疫器官的特性，并且由于其独特的结构和组织微环境，以及特定的细胞亚群和功能分子，形成了不同于全身性系统免疫的区域免疫特性，包括区域固有和适应性免疫特性及其中涉及的黏膜免疫特性。平衡的肺脏免疫调控机制对于维持肺部免疫稳态及抵抗病原微生物感染至关重要，而其失调则可导致感染性疾病的发生。因此，深入阐释肺脏区域免疫特性及其与感染性疾病的内在联系将有助于理解疾病的免疫病理机制，提供新的免疫治疗靶点和免疫防治策略，进而推进临床转化医学研究。     

免疫检查点抑制剂致免疫相关肝损伤的研究进展

近年来, 免疫检查点抑制剂(ICIs)在肿瘤患者的治疗中取得了很大进展, 延长了患者的生存期。然而, 在其增强免疫抗肿瘤的同时也可能造成免疫耐受失衡从而导致不同程度的免疫相关不良事件(irAEs)发生, ICIs致免疫相关肝损伤(ILICI)是其中较为常见的一种。主要对ILICI的定义、流行病学及危险因素、发病机制、病理及临床表现、治疗、复发及再治疗的研究进展进行综述。     

肠道菌群和黏膜免疫与心血管疾病关系研究新进展

心血管病是目前导致死亡的主要原因之一。引起心血管疾病的主要发生机制是免疫性炎症。肠道菌群与黏膜免疫相互作用，同心血管系统生理功能维持和疾病发生关系密切。肠道菌群失调会导致血管炎、高血压和动脉粥样硬化的发生及心衰的加重。深入了解肠道菌群、黏膜免疫和心血管疾病之间的相互作用机制，可为心血管疾病防治开创新思路。     

免疫抑制剂治疗IgA肾病的研究新进展

IgA肾病是最常见的免疫介导的原发性肾小球肾炎,是导致终末期肾病的主要原因,有着多种临床表现、病理特征和预后。免疫抑制剂,如环磷酰胺、硫唑嘌呤、来氟米特、霉酚酸酯等的使用对本病的治疗有一定的缓解率。本文主要回顾性地论述了不同的免疫抑制剂治疗IgA肾病的临床研究进展。     

舍格伦综合征诊断方法的研究进展

舍格伦综合征是一种慢性全身性自身免疫性疾病,其特点是外分泌腺(尤其是唾液腺和泪腺)的淋巴细胞浸润和炎症,导致口腔和眼部干燥。此外,多种器官系统也会受到影响,如肺、肾、肝、关节、皮肤等,同时伴有肌肉骨骼疼痛、慢性疲劳、血管炎等疾病。舍格伦综合征临床表现较复杂,病因和发病机制尚不明确,诊断标准和方法不统一,从而给临床诊断和...     

Deposits of immunoglobulins and C3 in the walls of human renal arteries.

Ninety-one renal biopsies were examined by immunofluorescent staining for the presence of C3 and immunoglobulins in the walls of renal arteries (RAW), tubules and glomeruli. The diseases studied were non-systemic renal immune complex diseases, systemic diseases with kidney involvement, renal diseases with minimal pathological changes and histological normal kidneys. In a high percentage of cases C3 and, to a lesser degree, deposits of immunoglobulins were found in the RAW, the deposits being found both in immunological and non-immunological diseases. Deposits of C3 but not of C4, C1q, fibrinogen, and immunoglobulins were found in the RAW of 11 normal kidneys examined.     

Significance of urinary C3 excretion in glomerulonephritis.

The third component of complement (C3) was measured in the urine of 98 patients with a variety of renal diseases. Renal biopsy was performed on 83 of the patients and examined by light, electron, and immunofluorescence microscopy. Urinary C3 was detected in cases of membranous glomerulonephritis, mesangiocapillary glomerulonephritis, rapidly progressive glomerulonephritis, and renal amuloidosis. It was not detected in minimal lesion glomerulonephritis; in cases of proliferative glomerulonephritis it was detected only in those showing histological evidence of a progressive lesion. Concentrations were low or undetectable in cases of non-immunological renal diseases. There was a good correlation between urinary C3 concentrations and the deposition of C3 in glomerular capillary walls, as seen by immunofluorescence microscopy, and there was no correlation with the degree or selectivity of proteinuria. Urinary C3 excretion appears to be an accurate indicator of continuing activity of disease. It is suggested that the presence of C3 in urine is due to complement fixation by immune complexes in glomerular capillary walls, and that urinary C3 estimations have potential applications in the study of glomerulonephritis.     

Does atrial natriuretic factor contribute to the progression of renal disease?

In chronic renal failure, non-immunological mechanisms may cause disease progression. It is postulated that the high plasma levels of atrial natriuretic factor which occur in some patients with chronic renal impairment are biologically active. They would not only serve to maintain sodium balance but also alter glomerular haemodymanics and enhance proteinuria to the long-term detriment of renal function.     

肾的体外诱导和干细胞治疗研究进展

随着干细胞的研究,肾脏疾患的干细胞治疗日益受到研究者的关注。拟就肾的体外诱导发育和肾疾病干细胞治疗的研究进展作一综述。包括：体外诱导胚肾组织发育;体外诱导干细胞向肾脏细胞的分化;骨髓、成体肾和胚胎肾来源的干细胞用于肾脏疾患治疗的研究。这些研究为临床部分或全部修复肾脏损伤提供了实验依据,也为肾损伤治疗提出了新的对策。     

Direct Cell Mediated Lympholysis. A Test of Allograft-Rejection in Human Kidney Recipients

In kidney transplanted patients a clear coincidence was observed between clinical signs of allograft rejection and the presence in the peripheral blood of killer cells able to lyse either PHA lymphoblasts from the actual donor or selected unrelated individuals. In recipients with non-immunological complications such as leakage on the graft ureter or primary anuria caused by renal ischaemia, no cellular cytotoxicity against specific or selected target cells was observed. The specificity of this Cell Mediated Lympholysis in two of the cases reported could not be explained by the serologically detectable HL-A antigens, indicating the existence of other determinants of importance for the killing capability of in vivo produced effector cells.     

Bacterial Histamine Release by Immunological and Non-Immunological Lectin-Mediated Reactions

The mechanisms of bacteria-induced histamine release were examined in vitro in human leukocytes and rat mast cells. Three types of bacterial responders were found. In persons with IgE-bearing basophilocytes bacterial histamine release could be triggered by two different mechanisms, an IgE-dependent mechanism where removal of IgE abolished the release and a non-immunological mechanism where this was not the case. In responders with no IgE-bearing cells bacterial histamine release was caused by a non-immunological mechanism. The non-immunological mechanism was further substantiated by release in isolated mast cells from germ-free rats. These experiments suggest a direct interaction between bacteria and target cell, and experiments with multi-washed bacteria and bacteria cell wall preparations indicate the possibility of the bacteria wall interacting with the target cell. It is probable that the non-immunological mechanism depends on lectin-mediated reactions, since bacteria-induced histamine release was inhibited by lectin-binding sugars as is release caused by plant lectins.     

The potential pathophysiological role of platelet-activating factor in human diseases

Summary Platelet-activating factor (PAF) is a new phospholipid mediator released from various cell types and tissues by the catalytic action of phospolipase A₂ and acetyl transferase upon immunological and non-immunological stimuli. It activates the cells by binding to specific binding sites. PAF exhibits a broad range of biological and pharmacological activities including platelet and neutrophil aggregation, eosinophil chemotaxis, bronchoconstriction, hypotension, and acute renal failure. In addition, PAF is involved in acute graft rejection, endotoxin shock, and gastrointestinal ulceration. Furthermore, it closely mimics the pathology of bronchial asthma and is cabable of producing most of the phenomena seen in inflammation. So far several PAF antagonists have been described and shown to afford protection. In future, pharmacological studies using such antagonists will help to elucidate the pathophysiological role of PAF in human diseases.Abbreviations Alkyl-acyl-GPC Alkyl-acyl-glyceryl-phosphorylcholine - A 23187 Calcium ionophore A 23187 - ECF-A Eosinophil chemotactic factor of anaphylaxis - GTP Guanosine triphosphate - IL-1 Interleukin-1 - Lyso-PAF 1-0-alkyl-glycero-3-phosphorylcholine - PAF Platelet-activating factor - TNF Tumour necrosis factor     

A comparison of the histamine-releasing properties of rat pleural and peritoneal mast cells.

A comparison has been made of the histamine-releasing characteristics of rat mast cells of pleural and peritoneal origin in response to a wide variety of immunological and non-immunological stimuli, namely, IgE antibody-antigen interaction; rabbit anti-rat antibody; concanvalin A (Con A); ACTH (1-24) polypeptide (Synacthen); a decapeptide comprising an amino acid sequence (497-506) within the human gamma-chain (Stanworth, Kings, Roy, Moran & Moran, 1979); adenosine triphosphate (ATP) and the calcium ionophore. This has provided valuable information about the relative responsiveness of target cells from two different sources within the same species. Pertioneal cells proved to be more responsive to basic polypeptide liberators, whereas pleural cells were considerably more responsive to stimuli mediated through IgE antibody, and slightly more responsive to challenge with non-immunological liberators. Interestingly, the histamine-release studies using an antiserum raised against mast cell IgE receptors have indicated that pleural mast cell membranes contain a higher density of IgE receptors than peritoneal mast cell membranes. Moreover, it was established that the amount of histamine release from either peritoneal or pleural mast cells effected by the polypeptide liberators was not influenced by the prior occupancy of the mast cell Fc receptors by rat IgE antibody.     

Tissue resident regulatory T cells: novel therapeutic targets for human disease

Over the past decade, the ability of regulatory T cells (Tregs) to suppress multiple types of immune cells has received tremendous attention. Mounting evidence has revealed that tissue resident Tregs control non-immunological processes of their target tissues and contribute to a plethora of human diseases. The identification of novel tissue-specific Tregs has highlighted their heterogeneity and complexity. This review summarizes the recent findings for visceral adipose tissue CD4+Foxp3+ regulatory T cells (VAT Tregs), muscle Tregs, bone Tregs and skin memory Tregs, with a focus on their unique functions in local tissues. This interpretation of the roles of tissue-specific Tregs and of their involvement in disease progression provides new insight into the discovery of potential therapeutic targets of human diseases.     

Parvovirus as a cause of hydrops fetalis: detection by in situ DNA hybridisation.

Lung tissue from 13 cases of unexplained non-immunological hydrops fetalis was examined by in situ hybridisation to detect parvovirus. Four specimens contained parvovirus DNA in cells in the blood vessel lumina and alveoli. Twenty six control cases were negative for parvovirus DNA. As there was no known epidemic of parvovirus infection during the study period, this suggests that parvovirus is a relatively common cause of non-immunological hydrops fetalis. In situ hybridisation may have a role in clinical medicine, particularly for retrospective investigations.