Regulation of homeostatic chemokine expression and cell trafficking during immune responses

The chemokines CCL21 and CXCL13 are immune factors that dictate homing and motility of lymphocytes and dendritic cells in lymphoid tissues. However, the means by which these chemokines are regulated and how they influence cell trafficking during immune responses remain unclear. We show that CCL21 and CXCL13 are transiently down-regulated within lymphoid tissues during immune responses by a mechanism controlled by the cytokine interferon-gamma. This modulation was found to alter the localization of lymphocytes and dendritic cells within responding lymphoid tissues. As a consequence, priming of T cell responses to a second distinct pathogen after chemokine modulation became impaired. We propose that this transient chemokine modulation may help orchestrate local cellularity, thus minimizing competition for space and resources in activated lymphoid tissues.     

A primitive T cell-independent mechanism of intestinal mucosal IgA responses to commensal bacteria

The immunoglobulin A (IgA) is produced to defend mucosal surfaces from environmental organisms, but host defenses against the very heavy load of intestinal commensal microorganisms are poorly understood. The IgA against intestinal commensal bacterial antigens was analyzed; it was not simply "natural antibody" but was specifically induced and responded to antigenic changes within an established gut flora. In contrast to IgA responses against exotoxins, a significant proportion of this specific anti-commensal IgA induction was through a pathway that was independent of T cell help and of follicular lymphoid tissue organization, which may reflect an evolutionarily primitive form of specific immune defense.     

Dynamic imaging of T cell-dendritic cell interactions in lymph nodes

T cell immune responses begin within organized lymphoid tissues. The pace, topology, and outcomes of the cellular interactions that underlie these responses have, so far, been inferred from static imaging of sectioned tissue or from studies of cultured cells. Here we report dynamic visualization of antigen-specific T cells interacting with dendritic cells within intact explanted lymph nodes. We observed immunological synapse formation and prolonged interactions between these two cell types, followed by the activation, dissociation, and rapid migration of T cells away from the antigenic stimulus. This high-resolution spatiotemporal analysis provides insight into the nature of cell interactions critical to early immune responses within lymphoid structures.     

The intraepithelial T cell response to NKG2D-ligands links lymphoid stress surveillance to atopy

Epithelial cells respond to physicochemical damage with up-regulation of major histocompatibility complex-like ligands that can activate the cytolytic potential of neighboring intraepithelial T cells by binding the activating receptor, NKG2D. The systemic implications of this lymphoid stress-surveillance response, however, are unknown. We found that antigens encountered at the same time as cutaneous epithelial stress induced strong primary and secondary systemic, T helper 2 (T(H)2)-associated atopic responses in mice. These responses required NKG2D-dependent communication between dysregulated epithelial cells and tissue-associated lymphoid cells. These data are germane to uncertainty over the afferent induction of T(H)2 responses and provide a molecular framework for considering atopy as an important component of the response to tissue damage and carcinogenesis.     

唇?成鱼脾和肾的解剖学与组织学特征

采用解剖、石蜡切片及HE染色技术研究了唇?脾脏、头肾及中肾的解剖学与组织学特征。结果显示,唇?脾脏单个,暗红色,呈扁平椭圆形,脾实质被起自被膜的结缔组织隔膜分隔成许多小叶,小叶内红髓与白髓界限不明显,含红细胞、淋巴细胞及黑色素巨噬细胞等,血管丰富。肾脏可明显的分为头肾和中肾。头肾位于体腔前端的心腹隔膜上方,分左右两叶,对称分布。头肾实质部分无肾单位,主要由淋巴组织构成,分红细胞聚集区和白细胞聚集区,内含丰富的红细胞、淋巴细胞、粒细胞及一定数量的黑色素巨噬细胞,在细胞组成上与脾脏有类似特征。中肾位于鱼体的胸腹段,紧贴体腔背部脊椎两侧,实质部分主要由肾单位、集合管及淋巴组织等构成;淋巴组织在细胞组成上与头肾有相似之处,含红细胞、淋巴细胞、粒细胞及黑色素巨噬细胞。研究结果表明,唇?脾脏、头肾是机体重要的免疫和造血器官,中肾除了泌尿功能外,在免疫及造血中也发挥重要作用。     

Thymic origin of intestinal alphabeta T cells revealed by fate mapping of RORgammat+ cells

Intestinal intraepithelial T lymphocytes (IELs) are likely to play a key role in host mucosal immunity and, unlike other T cells, have been proposed to differentiate from local precursors rather than from thymocytes. We show here that IELs expressing the alphabeta T cell receptor are derived from precursors that express RORgammat, an orphan nuclear hormone receptor detected only in immature CD4+CD8+ thymocytes, fetal lymphoid tissue-inducer (LTi) cells, and LTi-like cells in cryptopatches within the adult intestinal lamina propria. Using cell fate mapping, we found that all intestinal alphabeta T cells are progeny of CD4+CD8+ thymocytes, indicating that the adult intestine is not a significant site for alphabeta T cell development. Our results suggest that intestinal RORgammat+ cells are local organizers of mucosal lymphoid tissue.     

番鸭法氏囊相关淋巴组织的分布及组织学研究

研究了番鸭法氏囊柄部淋巴组织的分布及组织学结构。番鸭法氏囊柄部分布有多量的淋巴组织,以法氏囊柄的背侧淋巴组织分布面积最大、数量最多。其组织学结构包括淋巴相关上皮、上皮内淋巴细胞、圆顶区、淋巴滤泡以及高内皮静脉,其结构与其他粘膜相关淋巴组织相似。研究结果表明,分布于法氏囊柄部的淋巴组织是一种粘膜相关淋巴组织。     

Preferential localization of effector memory cells in nonlymphoid tissue

Many intracellular pathogens infect a broad range of host tissues, but the importance of T cells for immunity in these sites is unclear because most of our understanding of antimicrobial T cell responses comes from analyses of lymphoid tissue. Here, we show that in response to viral or bacterial infection, antigen-specific CD8 T cells migrated to nonlymphoid tissues and were present as long-lived memory cells. Strikingly, CD8 memory T cells isolated from nonlymphoid tissues exhibited effector levels of lytic activity directly ex vivo, in contrast to their splenic counterparts. These results point to the existence of a population of extralymphoid effector memory T cells poised for immediate response to infection.     

鲤鱼头肾显微结构研究

应用光镜对鲤鱼头肾的显微结构及其某些组织化学特性进行了研究。结果表明，头肾是鲤鱼的主要免疫器官，表面覆盖有一薄层纤维结缔组织性被膜，未见明显的小梁。实质主要由淋巴组织和血窦构成，可分为中央区及外周区。中央区的淋巴组织排列成索状，环绕血管呈放射状分布，细胞索之间由血窦隔开。外周区则以淋巴细胞排列密集的弥散性淋巴组织为特征。在头肾实擀中尚可见黑色素巨噬细胞中心、前肾间组织以及大小不一的甲状腺滤泡。     

Exploring and engineering the cell surface interface

Cells are inherently sensitive to local mesoscale, microscale, and nanoscale patterns of chemistry and topography. We review current approaches to control cell behavior through the nanoscale engineering of materials surfaces. Far-reaching implications are emerging for applications including medical implants, cell supports, and materials that can be used as instructive three-dimensional environments for tissue regeneration.     

Innate lymphoid cells promote anatomical containment of lymphoid-resident commensal bacteria

The mammalian intestinal tract is colonized by trillions of beneficial commensal bacteria that are anatomically restricted to specific niches. However, the mechanisms that regulate anatomical containment remain unclear. Here, we show that interleukin-22 (IL-22)-producing innate lymphoid cells (ILCs) are present in intestinal tissues of healthy mammals. Depletion of ILCs resulted in peripheral dissemination of commensal bacteria and systemic inflammation, which was prevented by administration of IL-22. Disseminating bacteria were identified as Alcaligenes species originating from host lymphoid tissues. Alcaligenes was sufficient to promote systemic inflammation after ILC depletion in mice, and Alcaligenes-specific systemic immune responses were associated with Crohn's disease and progressive hepatitis C virus infection in patients. Collectively, these data indicate that ILCs regulate selective containment of lymphoid-resident bacteria to prevent systemic inflammation associated with chronic diseases.     

Antireceptor antiserum causes specific inhibition of reactivity to rat histocompatibility antigens

The antigen receptor of lymphocytes destined to form antibody appears to have the characteristics of the immunoglobulin produced. Antibody directed against the combining region of this immunoglobulin should interact with the combining region of the cell receptor for the antigen. Purified Lewis rat alloantibody prepared against Brown Norway (BN) rat histocompatibility antigens was used to immunize L x BN F(1) hybrids. The resultant antiserum has anti-receptor activity because (i) it yields precipitin lines in gel diffusion when reacted against the immunizing alloantibody; (ii) it inhibits the hemagglutinin antibody response of Lewis rats to BN histocompatibility antigens; and (iii) it inhibits the local graft-versus-host response of Lewis lymphoid cells against BN antigens. This suggests that antireceptor antibody may inhibit cell-mediated responses as well as antibody responses to histocompatibility antigens and may play a role in the regulation of immune responses to such antigens.     

Biomaterial-centered infection: microbial adhesion versus tissue integration

Biomaterials are being used with increasing frequency for tissue substitution. Complex devices such as total joint replacements and the total artificial heart represent combinations of polymers and metal alloys for system and organ replacement. The major barriers to the extended use of these devices are the possibility of bacterial adhesion to biomaterials, which causes biomaterial-centered infection, and the lack of successful tissue integration or compatibility with biomaterial surfaces. Interactions of biomaterials with bacteria and tissue cells are directed not only by specific receptors and outer membrane molecules on the cell surface, but also by the atomic geometry and electronic state of the biomaterial surface. An understanding of these mechanisms is important to all fields of medicine and is derived from and relevant to studies in microbiology, biochemistry, and physics. Modifications to biomaterial surfaces at an atomic level will allow the programming of cell-to-substratum events, thereby diminishing infection by enhancing tissue compatibility or integration, or by directly inhibiting bacterial adhesion.     

Steroid binding at sigma receptors suggests a link between endocrine, nervous, and immune systems

Specific sigma binding sites have been identified in the mammalian brain and lymphoid tissue. In this study, certain gonadal and adrenal steroids, particularly progesterone, were found to inhibit sigma receptor binding in homogenates of brain and spleen. The findings suggest that steroids are naturally occurring ligands for sigma receptors and raise the possibility that these sites mediate some aspects of steroid-induced mental disturbances and alterations in immune functions.     

Pathogenesis of a local graft versus host reaction: immunogenicity of circulating host leukocytes

A local invasive-destructive reaction typical of that seen in allograft rejection occurs when Lewis rat spleen cells are inoculated under the capsule of Lewis kidney freshly grafted into F(1) hybrid hosts. Thus the donor lymphoid cells can be immunogenically stimulated by circulating host leukocytes and the interaction of these two cell populations results in nonspecific damage to kidney parenchyma. The results indicate that passenger leukocytes in organ allografts may be important immunogenic agents.     

Development of CD8alpha-positive dendritic cells from a common myeloid progenitor

Dendritic cells (DCs) are critical in both initiating adaptive immune responses and maintaining tolerance to self antigens. These apparently contradictory roles have been suggested to depend on different subsets of DCs that arise from either myeloid or lymphoid hematopoietic origins, respectively. Although DC expression of CD8alpha is attributed to a lymphoid origin, here we show that both CD8alpha+ and CD8alpha- DCs can arise from clonogenic common myeloid progenitors in both thymus and spleen. Thus, expression of CD8alpha is not indicative of a lymphoid origin, and phenotypic and functional differences among DC subsets are likely to reflect maturation status rather than ontogeny.     

Technique for normalizing intensity histograms of images when the approximate size of the target is known: Detection of feces on apples using fluorescence imaging

A challenge in machine vision is to develop algorithms for detecting a substance with an amorphous shape when measured responses of both the substance and the underlying target have similar characteristics. The challenge is exacerbated when responses for targets are highly variable both across and within discrete target units. An example of this problem is the detection of fecal contamination on apples. Feces on apples can be detected using differential fluorescence responses of contaminated and uncontaminated apple surfaces to UV excitation. However, responses of both feces and apples are due to the presence of chlorophyll-related compounds, and the response of apples varies within and between apples due to natural variation in the distribution of these compounds. We present a technique for normalizing the variability of intensity responses among targets based on a priori knowledge of the image dimensions and the approximate target size. Using this information, a linear equation is derived based on the approximate median intensities of the background and of the target. The median intensities are estimated by calculating a cumulative intensity histogram and using a priori estimates of the percentage of the area in the image occupied by the background and by a generic target. The image is scaled for uniform intensity power using this linear transformation. The benefits of using this technique are demonstrated using hyperspectral fluorescence responses to UV excitation of 48 Golden Delicious and 48 Red Delicious apples artificially contaminated with dilutions of cow feces. Results show that the uniform power transformation normalizes the intensity distributions of apple images and increases the contrast between contaminated and uncontaminated areas on apple surfaces; the coefficients of variation for the average intensities of uncontaminated apple surfaces at 668 nm for Golden and Red Delicious apples were reduced from 39 and 55%, respectively, to 5% for both varieties.     

兔圆小囊产溶菌酶细胞的免疫电镜组织化学观察

 采用免疫组织化学和免疫电镜细胞化学的方法 ,对兔圆小囊组织中产溶菌酶细胞进行了观察。免疫组织化学观察发现 ,产溶菌酶阳性细胞在兔圆小囊的粘膜上皮、圆顶上皮以及淋巴组织的滤泡生发中心、圆顶区和帽区均有分布 ,且受到多杀性巴氏杆菌感染后 ,阳性细胞增多 ,阳性反应增强。免疫电镜结果显示 ,在兔圆小囊的淋巴组织DNES细胞的颗粒中发现溶菌酶免疫组织化学阳性反应物。这一重要发现为神经 内分泌 免疫网络学说提供了新的证据。     

感染传染性法氏囊病毒雏鸡新城疫疫苗二次免疫的免疫增强效应

本实验以 IBDV 感染1日龄滨白雏鸡,在感染鸡14和28日龄或14日龄时点眼,滴鼻接种 Lasota 疫苗,测定了其外周血液、泪液、气管液、肠液、胆汁中 IgG,IgM 和 IgA 含量,血清、泪液、气管液 HI 滴度、血液 T 细胞免疫功能和脾脏 B 细胞抗体生成功能、血液 T、B 细胞和淋巴细胞数量以及法氏囊、胸腺、脾脏、盲肠扁桃体、哈德尔腺、丕氏斑、十二指肠、支气管粘膜的浆细胞和酸性α-萘酚酯酶阳性 T 细胞(ANAE~+T)数量的动态变化,结果表明:1.1 日龄感染 IBDV 雏鸡 ND 疫苗二次免疫后,其法氏囊,脾脏、哈德尔腺、支气管粘膜、盲肠扁桃体、丕氏斑、十二指肠粘膜固有层的浆细胞数量、外周血液 B 细胞数量均明显增高,脾脏 B 细胞抗体生成功能明显增强,血清、泪液、气管液中 IgG,IgA,IgM 含量和 HI 滴度、肠液、胆汁的 IgA,IgM,IgG 含量均显著高于感染一次免疫鸡,但明显低于健康对照二次免疫鸡。感染鸡 ND 二免后,法氏囊出现淋巴滤泡增生,脾脏和盲肠扁桃体的淋巴小结数量增多,直径增大。表明感染鸡 ND 二免后,其全身和消化道、呼吸道局部的体液免疫应答水平较感染一次免疫鸡明显增高,呈现免疫增强效应。2.感染鸡 ND 二免后,其免疫器官和消化道,呼吸道局部免疫组织的 ANAE~+T 细胞数量、外周血液 T 细胞数和免疫功能均较感染一免鸡明显升高。但显著低于对照 ND 二免鸡,证明感染鸡 ND 二免后,其全身和消化道、呼吸道局部的细胞免疫应答较感染一免鸡显著增强。3.ND 强毒攻击后,感染二免鸡的免疫保护率明显高于感染一免鸡,低于对照二免鸡,表明 ND 二次免疫对 IBDV 感染鸡的免疫保护力具有明显的加强作用,这与其全身和消化道、呼吸道局部的体液免疫和细胞免疫应答增强密切相关。