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1.
Bacterial contamination of the uterine lumen is common in cattle after parturition, often leading to infection and uterine disease. Clinical disease can be diagnosed and scored by examination of the vaginal mucus, which reflects the presence of pathogenic bacteria such as Escherichia coli and Arcanobacterium pyogenes. Viruses may also cause uterine disease and bovine herpesvirus 4 (BoHV-4) is tropic for endometrial cells, causing a rapid cytopathic effect. The elimination of pathogens by the innate immune system is dependent on pattern recognition receptors binding pathogen-associated molecules. Uterine epithelial and stromal cells express receptors such as Toll-like Receptor 4 that binds E. coli lipopolysaccharide. The infertility associated with uterine disease is caused by damage to the endometrium and disruption of ovarian cyclic activity. Bacteria modulate endometrial prostaglandin secretion, and perturb ovarian follicle growth and function. Understanding the molecular basis of uterine disease will lead to novel approaches to treating infertility.  相似文献   

2.
The innate immune system is essential for host defence and is responsible for early detection of potentially pathogenic microorganisms. Upon recognition of microbes by innate immune cells, such as macrophages and dendritic cells, diverse signalling pathways are activated that combine to define inflammatory responses that direct sterilisation of the threat and/or orchestrate development of the adaptive immune response. Innate immune signalling must be carefully controlled and regulation comes in part from interactions between activating and inhibiting signalling receptors. In recent years, an increasing number of pattern recognition receptors (PRRs), including C-type lectin receptors and Toll-like receptors (TLRs), has been described that participate in innate recognition of microbes, especially through the so called pathogen-associated molecular patterns (PAMPs). Recent studies demonstrate strong interactions between signalling through these receptors. Whereas useful models to study these receptors in great detail in the murine and human system are now emerging, relatively little is known regarding these receptors in companion and farm animals. In this review, current knowledge regarding these receptors in species of veterinary relevance is summarised.  相似文献   

3.
The skin is a complex and dynamic ecosystem, wherein epithelial cells, immune cells and the skin microbiota actively interact and maintain barrier integrity and functional immunity. Skin microbes actively tune the functions of the resident immune cells. Dysbiosis – alterations in the resident microbiota – leads to the dysregulation of host immunity. Microbiome analyses in humans and dogs with atopic dermatitis (AD) have shown shifts in microbial diversity, and in particular, an increased proportion of staphylococci. Monogenic diseases that manifest AD-like symptoms provide insights into the pathogenesis of AD and the mechanisms of dysbiosis, from both the epithelial and immunological perspectives. The symbiotic relationships between the host and microbiota must be maintained constitutively. Detailed mechanisms of how host immunity regulates commensal bacteria in the steady state have been reported. The skin harbours multiple tissue-resident immune cells, including both innate and adaptive immune cells. Recent studies have highlighted the fundamental role of innate lymphoid cells (ILCs) in the maintenance of barrier functions and tissue homeostasis. ILCs directly respond to tissue-derived signals and are instrumental in barrier immunity. Epithelial cells produce alarmins such as thymic stromal lymphopoietin (TSLP) and interleukins (IL)-33 and IL-25, all of which activate group 2 ILCs (ILC2s), which produce type 2 cytokines, such as IL-5 and IL-13, boosting type 2 immune reactions. Dysregulation of the epithelial–ILC crosstalk results in allergic inflammation. This review highlights our understanding of the active interactions between the host epithelial and immune cells, and microbiota, providing a foundation for novel therapeutic strategies for inflammatory skin diseases.  相似文献   

4.
轮状病毒(RV)是引起婴幼儿、幼畜禽急性肠胃炎的人畜共患病原,常与其他病原体混合感染,多以呕吐,严重水样腹泻,脱水为临床症状,感染后具有较高病死率,对人类公共卫生以及养殖业造成极大危害.RV病原相关分子模式(PAMP)可被肠上皮细胞(IECs)中一组可遗传的模式识别受体(PRR)识别,通过IECs、先天免疫细胞与RV互...  相似文献   

5.
The gut maintains a delicate balance between the downregulation of inflammatory reactions to commensal bacteria and the capacity to respond to pathogens with vigorous cellular and humoral immune responses. Intestinal epithelial cells, including colonic epithelial cells (CECs) possess many properties of cells of the innate immune system, in particular the ability to recognize and respond to microbial antigens. Recognition of microorganisms by CECs is based upon their recognition of signature molecules, called microbe-associated molecular patterns (MAMP), by pattern recognition receptors (PRR) including membrane toll-like receptors (TLR) and cytosolic Nod2, an intracellular counterpart of TLRs. The purpose of this study was to determine whether primary CECs from normal dogs express a functional TLR2, TLR4, and Nod2 and whether they are regulated by inflammatory mediators. We show that canine primary CECs express TLR2, TLR4, and Nod2 that can be modulated in response to their respective MAMPs, lipopolysaccharides (LPS) or peptidoglycans (PGN). Furthermore, we demonstrate that these receptors are functional as evidenced by the induction of cytokine gene expression in response to LPS or PGN.  相似文献   

6.
Toll-like receptors (TLR) are a group of pattern recognition molecules that play a crucial role in innate immunity. TLR2 recognises a variety of microbial components leading to the development of inflammatory and immune responses. To characterise the expression and functional properties of porcine TLR2 (pTLR2), we have raised a panel of monoclonal antibodies (mAb) against this molecule. Mouse 3T3 cell transfectants expressing pTLR2 were used for immunisation of mice. The specificity of these antibodies was confirmed by their reactivity with CHO cells transfected with pTLR2 but not with pTLR4 or with non-transfected cells. Using one of these mAbs, named 1H11, pTLR2 was found on cells of the innate immune system, including monocytes, macrophages, and granulocytes, but not on peripheral blood lymphocytes. Staining of tissue sections showed that pTLR2 is also expressed on epithelial cells lining the tracheobronchial and intestinal tracts, bile ducts in the liver and renal tubules, and on the basal layer of the epidermis. This distribution is consistent with a surveillance function at entry sites, allowing for early detection of microbial invasion.  相似文献   

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8.
宋宇琨  何俊 《中国畜牧兽医》2020,47(6):1709-1718
脾脏作为猪最大的次级淋巴器官,含有多种免疫活性细胞和免疫因子,是先天性免疫和适应性免疫重要的应答场所,具有广泛的免疫调控功能;同时可清除衰老、损伤红细胞及过滤病原体,并在造血和储藏血细胞方面具有重要作用。这些功能与脾脏的结构密切相关,其中红髓主要作为血液滤过器,执行造血、储血和清除异物的功能;白髓是免疫的主要区域,含有多种免疫细胞,可执行特异性免疫应答调控功能;而边缘区是连接两个区室的重要桥梁,使所有细胞和抗原都能通过其进入脾脏不同部位。不同的发育和免疫关键基因是实现脾脏功能的根本,发育基因的表达保证了其结构的完整,为脾脏执行各种功能提供空间。免疫关键基因的表达确保了免疫反应进行,其中不同模式识别受体基因的表达保证了先天性免疫的吞噬和识别应答,而各种免疫细胞分泌的多种细胞因子和免疫活性物质是获得性免疫反应的基础,实现机体清除和监控抗原的生理过程。随着脾脏研究的深入,对其各种免疫细胞和免疫功能有了新的认识。作者首先阐述了脾脏组织不同区域的生物学功能;然后结合机体免疫应答机制,论述脾脏先天性和特异性免疫功能以及所需免疫细胞和免疫因子的作用与关联;最后简单介绍了脾脏胚胎期和出生后期的组织发育和免疫相关基因,总结了猪脾脏先天性免疫中重要的模式识别受体及其基因家族,为研究猪脾脏先天性免疫功能提供参考。  相似文献   

9.
Veterinary Research Communications - Endometrial epithelial cells play a key defensive role as part of the innate immune response of cow uterus. An association between risk of acquiring infectious...  相似文献   

10.
Interleukin-18 (IL-18) is a proinflammatory cytokine involved in chronic inflammation, autoimmune diseases, and a variety of cancers, and is expressed in mouse uteri. Our previous study suggested that IL-18 acts as a paracrine factor, regulating endometrial function. To elucidate the physiological roles of IL-18 in the mouse endometrium, the expression of the IL-18 receptor (IL-18R) alpha subunit was analyzed. IL-18Ralpha mRNA was expressed in several mouse organs in addition to the endometrium. In situ hybridization analysis using a biotin-labeled mouse IL-18Ralpha riboprobe demonstrated that IL-18Ralpha mRNA expression was detected in glandular epithelial cells, stromal cells around uterine glands, and myometrial cells in the mouse uterus, suggesting that these cells are targets for IL-18. The uterine IL-18Ralpha mRNA expression level changed with the estrous cycle. The uterine IL-18Ralpha mRNA levels of estrous mice were higher than those of diestrous mice. In addition, the IL-18Ralpha mRNA levels in uteri at 3 and 14 days after ovariectomy were higher than those at diestrus and decreased following treatment with estradiol-17beta or progesterone. These findings suggest that IL-18Ralpha gene expression is regulated by estrogen and progesterone and that the uterine IL-18 system is involved in the regulation of uterine functions in a paracrine manner.  相似文献   

11.
细胞因子是免疫活性细胞和其它细胞分泌的具有多种生物活性的多肽或蛋白质,这些细胞因子是重要的信息传递物质,特别在免疫、炎症和造血系统等生物学反应过程中具有重要的作用。细胞因子用于重组疫苗上的研究已成为生物学研究中最活跃的领域之一。在基因工程疫苗研制中,常把细胞因子基因(如IL-2、IL-1等)和保护抗原基因连接在一起,构成融合蛋白.以增强疫苗的抗体产生和细胞免疫水平。以干扰素和白细胞介素为例,叙述了细胞因子在免疫增强剂和免疫治疗剂、构建新型基因工程苗等方面的主要研究进展。  相似文献   

12.
β-Defensins are small cationic molecules that have antimicrobial actions against bacteria, fungi and viruses and contribute to mucosal immune responses at epithelial sites. The female reproductive tract is an important site of defensin production. This study was conducted to determine the possible changes in proportions and localization of β-defensin 1-4 in the rat uterus at the 1st, 3th, 5th, 10th and 15th days of postpartum and at the period of diestrus using immunohistochemical techniques. In the present study, it was determined that β-defensin 1-4 were generally found in all structural components of the endometrium (luminal and glandular epithelium, stromal cells and blood vessels) in both the nucleus and the cytoplasm of cells during the involution period and diestrus. Suprisingly, immunoreaction of β-defensin 2 was also observed in the lateral membrane of the luminal and glandular epithelial cells on the 10th day of involution and immunostaining of β-defensin 4 was also localized in the apical membrane of the luminal and glandular epithelial cells. The current study demonstrated β-defensin 1-4 immunoreactivities in the endothelium of blood vessels were stronger throughout the involution period. Although β-defensins 2 and 3 were localized in both the nuclei and the cytoplasm of endothelial cells, β-defensins 1 and 4 were present in only cytoplasm. These results show that the most component of rat endometrium expresses human β-defensin 1-4 in a involution-dependent manner. Therefore it may be asserted that these molecules constitute a organised protection to prevent uterus from probable infections during the involution process.  相似文献   

13.
皮肤和黏膜上皮细胞既是机体的物理屏障,又是机体防御微生物的第一道防线。上皮细胞与白细胞、树突细胞(DCs)等之间的相互作用,是机体产生适应性免疫反应的重要因素。IL-17细胞因子家族是最近新发现的具有强大的促炎症作用的细胞因子,它们在机体的固有和适应性免疫中发挥着重要作用,IL-17A、IL-17C和IL-17F能够直接作用于组织的上皮细胞,诱导各种免疫反应来对抗病原体,且能够促进组织的修复。IL-17E最基本的作用是作用于白细胞和诱导Ⅱ型免疫,这在其对抗寄生虫的作用中是非常关键的,此外,IL-17E还可以反向调节白细胞对IL-17A和IL-17F的产生;而对于IL-17B和IL-17D的研究则相对较少一些。  相似文献   

14.
Activation of the innate immune system requires recognition of pathogen-associated molecular patterns, such as NOD-like receptors. The NOD-like receptor protein 3 (NLRP3) inflammasome is involved in induction of the pro-inflammatory cytokine, IL-1β, and subsequent inflammatory responses. NLRP3 inflammasome plays important roles in the inflammatory and innate immune responses associated with autoimmune/inflammatory syndrome. However, analysis of the tissue distribution and expression profiles in BALB/c mice is still incomplete. In this study, we investigated the tissue distribution and expression pattern of NLRP3 in BALB/c mice to further elucidate its function in innate immunity in this commonly used laboratory animal model. NLRP3 mRNA expression levels and tissue distribution of the protein were investigated by real-time quantitative PCR and immunohistochemical analyses, respectively. NLRP3 mRNA expression was higher in the kidney and inguinal lymph nodes than in other tissues. Cytoplasmic expression of NLRP3 was detected in the epithelial reticular cells of the spleen and thymus, lymphocytes in the inguinal lymph nodes, cardiac muscle cells, cerebral cortex neurons, alveolar macrophages, renal tubule cells and liver sinusoidal endothelial cells. The results of this study will assist investigators in interpreting site-specific functions and roles of NLRP3 in inflammatory responses.  相似文献   

15.
16.
Toll样受体研究进展   总被引:4,自引:0,他引:4  
免疫系统识别"非我"和"自我"的过程是依赖于不同的受体来完成的,作为先天性免疫系统的重要组成部分及连接获得性免疫与先天性免疫的"桥梁",Toll样受体(Toll-like receptors,TLRs)是生物的一种模式识别受体(pattern recognition receptor,PRR),它主要通过识别病原相关分子模式(pathogen-associated molecularpatterns,PAMPs)来启动免疫反应。已发现TLRs在炎症、细胞信号转导、细胞凋亡、肿瘤等发生过程中扮演重要角色。随着分子细胞生物学的发展,有关TLRs的研究必将更加深入,同时也会进一步拓展对机体免疫机制的认识。  相似文献   

17.
Toll样或非Toll样配体佐剂研究进展   总被引:1,自引:0,他引:1  
有效的疫苗含有可活化天然免疫系统的佐剂组分,从而激发抗原特异性的免疫应答.Toll样受体(toll-like receptors,TLR)是一种重要的天然识别受体,大多数疫苗佐剂都是TLR配体.少数佐剂通过其他的识别受体和信号通路,以TLR非依赖性的方式来活化天然免疫系统.非Toll样配体佐剂的作用靶点主要是近来发现的NOD样受体(Nod-like receptor,NLR)、RIG(retinoic-acid-inducible gene)样受体(RIG-like receptors,RLR)等胞内天然免疫受体.文章对Toll样或非Toll样配体作为疫苗佐剂的研究进行了综述.  相似文献   

18.
19.
TOLL-like receptors linking innate and adaptive immune response   总被引:25,自引:0,他引:25  
Invading pathogens are controlled by the innate and adaptive arms of the immune system. Adaptive immunity, which is mediated by B and T lymphocytes, recognises pathogens by rearranged high affinity receptors. However, the establishment of adaptive immunity is often not rapid enough to eradicate microorganisms as it involves cell proliferation, gene activation and protein synthesis. More rapid defense mechanisms are provided by innate immunity, which recognises invading pathogens by germ-line-encoded pattern recognition receptors (PRR). Recent evidence shows that this recognition can mainly be attributed to the family of TOLL-like receptors (TLR). Binding of pathogen-associated molecular patterns (PAMP) to TLR induces the production of reactive oxygen and nitrogen intermediates (ROI and RNI), pro-inflammatory cytokines, and up-regulates expression of co-stimulatory molecules, subsequently initiating the adaptive immunity. In this review, we will summarize the discovery and the critical roles of the TLR family in host defense, briefly allude to signaling mechanisms mediating the response to TLR ligands, and will provide an update on current knowledge regarding the ligand specificity of these receptors and their role in immunity of domestic animals, particularly cattle.  相似文献   

20.
Expression and function of Toll-like receptor 2 in canine blood phagocytes   总被引:2,自引:0,他引:2  
Toll-like receptors (TLRs) are a family of highly conserved pattern recognition receptors (PRR) of mammals that participate in the activation of innate immune responses against microbial infections. Among these receptors, TLR2 is essential for the recognition of conserved structural components of bacteria, protozoa and fungi. Until now, expression of TLR2 in dogs has not been investigated. In this work we describe a partial sequence of the gene coding for canine TLR2 and show that TLR2 mRNA is constitutively expressed in canine blood PMNs. We also show that stimulation of purified PMNs with lipoteichoic acid (LTA), a ligand of TLR2, leads to the release of proinflammatory chemokine IL-8. Furthermore, TLR2 protein is easily detectable by flow cytometry on the canine peripheral blood granulocyte and monocyte cell surface, and slightly on lymphocytes. These findings suggest that, also in dogs as in humans the initial antibacterial response of PMNs could be elicited through engagement of TLR2.  相似文献   

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