Function Of Lymphoid Organs Research Articles

Application of Nanomaterials in the Repair and Regeneration of Lymphatic Organs and Corresponding Biophysical Simulation Strategies

Immune system diseases, malignant tumors, and traumatic injuries can directly damage the structure and function of lymphoid organs, while subsequent radiotherapy, chemotherapy, and lymph node dissection further damage the patient's immune system, leading to immune dysfunction, metabolic disorders, and increased susceptibility to infection, which seriously affect the patient's prognosis and quality of life. In this context, nanotechnology plays a key role in lymphoid organ regeneration and immune function recovery, including improving the therapeutic effect through targeted drug delivery systems, using targeted imaging probes to achieve tumor prediction and early detection, combining nanoplatforms with immunotherapy and photodynamic therapy to achieve synergistic therapeutic effects, and using nanomaterials to regulate the tumor microenvironment to enhance the sensitivity of traditional treatments. In addition, biophysical simulation strategies that simulate the microenvironment of lymphoid organs have also attracted widespread attention, aiming to construct a native cell environment to support the regeneration and functional recovery of damaged lymphoid tissues, or to simulate immune cells to regulate lymphocytes and induce specific immune responses. The multifaceted application of nanotechnology provides promising prospects for lymphoid organ regeneration and immune system repair.

Adaptive immunity and atherosclerosis: aging at its crossroads.

Adaptive immunity plays a profound role in atherosclerosis pathogenesis by regulating antigen-specific responses, inflammatory signaling and antibody production. However, as we age, our immune system undergoes a gradual functional decline, a phenomenon termed "immunosenescence". This decline is characterized by a reduction in proliferative naïve B- and T cells, decreased B- and T cell receptor repertoire and a pro-inflammatory senescence associated secretory profile. Furthermore, aging affects germinal center responses and deteriorates secondary lymphoid organ function and structure, leading to impaired T-B cell dynamics and increased autoantibody production. In this review, we will dissect the impact of aging on adaptive immunity and the role played by age-associated B- and T cells in atherosclerosis pathogenesis, emphasizing the need for interventions that target age-related immune dysfunction to reduce cardiovascular disease risk.

Intravital microscopy: Imaging host-parasite interactions in lymphoid organs.

Intravital microscopy allows imaging of biological phenomena within living animals, including host-parasite interactions. This has advanced our understanding of both, the function of lymphoid organs during parasitic infections, and the effect of parasites on such organs to allow their survival. In parasitic research, recent developments in this technique have been crucial for the direct study of host-parasite interactions within organs at depths, speeds and resolution previously difficult to achieve. Lymphoid organs have gained more attention as we start to understand their function during parasitic infections and the effect of parasites on them. In this review, we summarise technical and biological findings achieved by intravital microscopy with respect to the interaction of various parasites with host lymphoid organs, namely the bone marrow, thymus, lymph nodes, spleen and the mucosa-associated lymphoid tissue, and present a view into possible future applications.

High Endothelial Venules and Other Blood Vessels: Critical Regulators of Lymphoid Organ Development and Function.

The blood vasculature regulates both the development and function of secondary lymphoid organs by providing a portal for entry of hemopoietic cells. During the development of lymphoid organs in the embryo, blood vessels deliver lymphoid tissue inducer cells that initiate and sustain the development of lymphoid tissues. In adults, the blood vessels are structurally distinct from those in other organs due to the requirement for high levels of lymphocyte recruitment under non-inflammatory conditions. In lymph nodes (LNs) and Peyer’s patches, high endothelial venules (HEVs) especially adapted for lymphocyte trafficking form a spatially organized network of blood vessels, which controls both the type of lymphocyte and the site of entry into lymphoid tissues. Uniquely, HEVs express vascular addressins that regulate lymphocyte entry into lymphoid organs and are, therefore, critical to the function of lymphoid organs. Recent studies have demonstrated important roles for CD11c+ dendritic cells in the induction, as well as the maintenance, of vascular addressin expression and, therefore, the function of HEVs. Tertiary lymphoid organs (TLOs) are HEV containing LN-like structures that develop inside organized tissues undergoing chronic immune-mediated inflammation. In autoimmune lesions, the development of TLOs is thought to exacerbate disease. In cancerous tissues, the development of HEVs and TLOs is associated with improved patient outcomes in several cancers. Therefore, it is important to understand what drives the development of HEVs and TLOs and how these structures contribute to pathology. In several human diseases and experimental animal models of chronic inflammation, there are some similarities between the development and function of HEVs within LN and TLOs. This review will summarize current knowledge of how hemopoietic cells with lymphoid tissue-inducing, HEV-inducing, and HEV-maintaining properties are recruited from the bloodstream to induce the development and control the function of lymphoid organs.

Age-related changes in the structure of lymphoid organs: A review of the literature

Numerous and rather contradictory research data demonstrate that the mechanism of increased susceptibility to diseases in old age so far has no satisfactory explanation. Concurrently, the relevant literature almost lacks any comparative data on the specific features on the effect of surgeries and traumas on the structure and function of lymphoid organs in patients of different age cohorts. However, lymph nodes mark the activity of local inflammation, and changes in them allow the estimation of treatment efficiency, as well as the prognosis and prevention of many complications. This is especially important with the constant increase in the average age and life expectancy in the human population and the more active use of surgeries in elder and old patients.

Pairing experimentation and computational modeling to understand the role of tissue inducer cells in the development of lymphoid organs

The use of genetic tools, imaging technologies and ex vivo culture systems has provided significant insights into the role of tissue inducer cells and associated signaling pathways in the formation and function of lymphoid organs. Despite advances in experimental technologies, the molecular and cellular process orchestrating the formation of a complex three-dimensional tissue is difficult to dissect using current approaches. Therefore, a robust set of simulation tools have been developed to model the processes involved in lymphoid tissue development. Specifically, the role of different tissue inducer cell populations in the dynamic formation of Peyer’s patches has been examined. Utilizing approaches from systems engineering, an unbiased model of lymphoid tissue inducer cell function has been developed that permits the development of emerging behaviors that are statistically not different from that observed in vivo. These results provide the confidence to utilize statistical methods to explore how the simulator predicts cellular behavior and outcomes under different physiological conditions. Such methods, known as sensitivity analysis techniques, can provide insight into when a component part of the system (such as a particular cell type, adhesion molecule, or chemokine) begins to have an influence on observed behavior, and quantifies the effect a component part has on the end result: the formation of lymphoid tissue. Through use of such a principled approach in the design, calibration, and analysis of a computer simulation, a robust in silico tool can be developed which can both further the understanding of a biological system being explored, and act as a tool for the generation of hypotheses which can be tested utilizing experimental approaches.

Abundantly expressed transcripts in the lymphoid organ of the black tiger shrimp, Penaeus monodon, and their implication in immune function

The lymphoid organ of penaeid shrimps is proposed to play an important role in the innate immune system. To investigate the potential immune function of the lymphoid organ, we analyzed the expressed genes from the lymphoid organ of normal and Vibrio harveyi-infected Penaeus monodon using an expressed sequence tag (EST) approach. Sequence analysis of the EST clones derived from the two lymphoid organ cDNA libraries (408 clones from the normal and 625 clones from the infected libraries), revealed a high redundancy of specific transcripts. Transcripts of the lysosomal cysteine proteinases, cathepsins B and L, were abundantly expressed in the lymphoid organ of both libraries, whilst the transcripts of the related genes peritrophin and thrombospondin predominated and were found only in the V. harveyi-infected library, making them interesting candidate functional genes. Moreover, immune-related genes were found at a significant proportion (approximately 15%) in both normal and infected libraries, but different expressed genes were observed between the two libraries. The expression levels of P. monodon cathepsins B and L in the lymphoid organ following injection with either V. harveyi or white spot syndrome virus (WSSV) showed only a slight change in the transcript abundance compared to that seen in the mock-infection (control). Immunohistochemistry confirmed that cathepsin L protein was localized in the lymphoid organ with intense cathepsin L staining observed in the lymphoid organ spheroids of WSSV-infected shrimps. The results suggest that cathepsins L and B likely play a major role in the lymphoid organ function and are probably implicated in degradation of foreign material that is sequestrated in the lymphoid organ spheroids, although any additional role in control of viral or cellular mediated apoptosis remains to be evaluated.

Functional analysis of neuropeptides in avian thymocyte development

The function of lymphoid organs and immune cells is often modulated by peptides and hormones produced by the neuroendocrine and immune systems. We have previously reported the intrathymic expression of neuropeptides in the thymus of different species and that neuropeptides can influence murine thymocyte development in vitro. To further explore the evolutionary nature of neuroendocrine interactions in the thymus, we identified the expression of calcitonin-gene-related peptide, neuropeptide Y, somatostatin (SOM), substance P and vasointestinal polypeptide, as well as their receptors on chicken thymic epithelial cells (TEC) and thymocytes by immunofluorescence and reverse transcription polymerase chain reaction (RT-PCR). All the studied neuropeptides and their receptors were found to be expressed in both TEC and thymocytes, suggesting that intrathymic neuroendocrine interactions may take place within the avian thymus. In order to elucidate whether such interactions play a role in avian thymocyte development, neuropeptides and their antagonists were added to embryonic thymus organ cultures and found to influence chicken thymopoiesis. In particular, an antagonist of SOM increased the proportion of double-positive thymocytes, while SOM itself appeared to inhibit the early stages of thymocyte development. Taken together, these data provide further evidence to suggest that neuropeptides play a conserved role in vertebrate thymocyte development.

Evolutionary conservation of neuropeptide expression in the thymus of different species

Evidence suggests that the immune and neuroendocrine systems cross talk by sharing ligands and receptors. Hormones and neuropeptides produced by the neuroendocrine system often modulate the function of lymphoid organs and immune cells. We have previously reported the intrathymic expression of somatostatin (SOM) in the mouse and that several neuropeptides, most notably calcitonin-gene-related peptide (CGRP), neuropeptide Y (NPY), SOM and substance P (SP), can modulate thymocyte development. However, little is known about the intrathymic expression of these neuropeptides either in the mouse or in other species. Moreover, a comparative analysis of the expression of these molecules would highlight the evolutionary importance of intrathymic neuroendocrine interactions in T-cell development. We have studied the expression of different neuropeptides in the thymus of zebrafish, Xenopus, avians, rodent, porcine, equine and human by immunohistochemistry and reverse transcription-polymerase chain reaction. We found that CGRP, NPY, SOM, SP and vasointestinal polypeptide (VIP) are expressed in the thymus of all species investigated. The thymic location of many of these neuropeptides was conserved and appears to be within the stromal compartments. Interestingly, in the avian thymus the expression of CGRP, SOM and SP appears to change depending on the age of the tissue. These findings suggest that neuropeptides may play an important role in T-cell development and provide further evidence of cross talk between the immune and neuroendocrine systems.

Prevention of acute graft-versus-host disease despite compensatory function of lymphoid organs in vivo

Acute graft-versus-host disease (aGVHD) results from alloreactive donor derived T cells attacking targets in the gastrointestinal tract, liver and skin. We observed the initiation and rapid kinetics of aGVHD in a murine model [FVB/N (H-2q) into irradiated Balb/c (H-2d)] using in vivo bioluminescence imaging. The transition from the initiation to the effector phase of aGVHD (day 3–4) was characterized by rapid T cell proliferation and upregulation of gut homing receptors alpha4beta7, alphaEbeta7 and CCR9 on alloreactive T cells in Peyer’s patches (PP), mesenteric lymph nodes (LN) and spleen, but not peripheral LNs. Therefore we asked whether the lack of specific lymphoid priming sites would lead to decreased alloreactive T cell infiltration in the gut compared to the liver and skin. Using PP deficient mice, we observed that mesenteric LN and spleen compensate for the lack of PP as alloreactive priming sites. Transplantation of PP and LN deficient mice (TNFalpha-/-) showed that the spleen alone was sufficient to cause the complete profile of aGVHD with a time course similar to that of wildtype mice. Splenectomized mice with intact secondary lymphoid organs also developed aGVHD. Strikingly, treatment of splenectomized recipients with blocking antibodies against the lymphoid homing receptors L-selectin and MAdCAM-1 prevented GVHD with 100% survival (>120 d, p<0.0001). Our study shows that multiple priming sites are involved in GVHD initiation, the spleen compensating for the lack of PP and mesenteric LN, and vice versa. In contrast, splenectomy and antibody blocking resulted in a clear survival benefit for all recipients.

Prevention of Acute Graft-Versus-Host Disease Despite Compensatory Function of Lymphoid Organs In Vivo.

Acute graft-versus-host disease (aGVHD) results from alloreactive donor derived T cells attacking targets in the gastrointestinal tract, liver and skin. We observed the initiation and rapid kinetics of aGVHD in a murine model [FVB/N (H-2q) into irradiated Balb/c (H-2d)] using in vivo bioluminescence imaging. The transition from the initiation to the effector phase of aGVHD (day 3–4) was characterized by rapid T cell proliferation and upregulation of gut homing receptors alpha4beta7, alphaEbeta7 and CCR9 on alloreactive T cells in Peyer's patches (PP), mesenteric lymph nodes (LN) and spleen, but not peripheral LNs. Therefore we asked whether the lack of specific lymphoid priming sites would lead to decreased alloreactive T cell infiltration in the gut compared to the liver and skin. Using PP deficient mice, we observed that mesenteric LN and spleen compensate for the lack of PP as alloreactive priming sites. Transplantation of PP and LN deficient mice (TNFalpha-/-) showed that the spleen alone was sufficient to cause the complete profile of aGVHD with a time course similar to that of wildtype mice. Splenectomized mice with intact secondary lymphoid organs also developed aGVHD. Strikingly, treatment of splenectomized recipients with blocking antibodies against the lymphoid homing receptors L-selectin and MAdCAM-1 prevented GVHD with 100% survival (>120 d, p<0.0001). Our study shows that multiple priming sites are involved in GVHD initiation, the spleen compensating for the lack of PP and mesenteric LN, and vice versa. In contrast, splenectomy and antibody blocking resulted in a clear survival benefit for all recipients.

Lymphoid organ development and cell migration.

As we travel into a new century, confronted with new infectious diseases and bioweapon threats, with surgeons continuing to push the boundaries of what is transplantable, and with gene therapists working on ways to remedy a myriad of genetic diseases, the need for improved methods to augment and suppress immune function is paramount. The recent discovery that a novel immunosuppressant works by blocking lymphocyte egress from lymphoid organs provides a compelling example of how improved understanding of lymphoid organ function will contribute to future drug development and human health. This volume brings together reviews from leaders in the field of thymus and secondary lymphoid organ biology, including discussions on the roles of transcriptional regulators Foxn1, retinoid-related orphan receptor gamma and nuclear factor-kappaB in lymphoid organ development, the function of lymphotoxin and other cytokines in lymphoid tissue organization, the guidance activity of chemokines in a multitude of immune cell-positioning events, the mechanism of action of the immunosuppressant FTY720, and the application of two-photon laser scanning microscopy to reveal the dynamic behavior of lymphoid cells in the depths of these essential tissues.

Geertruida Jeanette Thorbecke (1929–2001)

Geertruida Jeanette Thorbecke (1929–2001)

Androgens and oestrogens may modulate the growth and function of lymphoid organs.

Androgens and oestrogens may modulate the growth and function of lymphoid organs.