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Trends in Immunology May 2014The mammalian immune system is tasked with protecting the host against a broad range of threats. Understanding how immune populations leverage cellular diversity to... (Review)
Review
The mammalian immune system is tasked with protecting the host against a broad range of threats. Understanding how immune populations leverage cellular diversity to achieve this breadth and flexibility, particularly during dynamic processes such as differentiation and antigenic response, is a core challenge that is well suited for single cell analysis. Recent years have witnessed transformative and intersecting advances in nanofabrication and genomics that enable deep profiling of individual cells, affording exciting opportunities to study heterogeneity in the immune response at an unprecedented scope. In light of these advances, here we review recent work exploring how immune populations generate and leverage cellular heterogeneity at multiple molecular and phenotypic levels. Additionally, we highlight opportunities for single cell technologies to shed light on the causes and consequences of heterogeneity in the immune system.
Topics: Animals; Gene Expression Regulation; Genetic Heterogeneity; Humans; Immune System; Immunity; Lymphoid Tissue; Phenotype; Protein Processing, Post-Translational
PubMed: 24746883
DOI: 10.1016/j.it.2014.03.004 -
BMC Immunology Jan 2018The lymphatic vascular pattern in the head of mice has rarely been studied, due to problems of sectioning and immunostaining of complex bony structures. Therefore, the...
BACKGROUND
The lymphatic vascular pattern in the head of mice has rarely been studied, due to problems of sectioning and immunostaining of complex bony structures. Therefore, the association of head lymphoid tissues with the lymphatics has remained unknown although the mouse is the most often used species in immunology.
RESULTS
Here, we studied the association of nasal and nasolacrimal duct lymphatics with lymphoid aggregates in 14-day-old and 2-month-old mice. We performed paraffin sectioning of whole, decalcified heads, and immunostaining with the lymphatic endothelial cell-specific antibodies Lyve-1 and Podoplanin. Most parts of the nasal mucous membrane do not contain any lymphatics. Only the region of the inferior turbinates contains lymphatic networks, which are connected to those of the palatine. Nose-associated lymphoid tissue (NALT) is restricted to the basal parts of the nose, which contain lymphatics. NALT is continued occipitally and can be found at both sides along the sphenoidal sinus, again in close association with lymphatic networks. Nasal lymphatics are connected to those of the ocular region via a lymphatic network along the nasolacrimal duct (NLD). By this means, lacrimal duct-associated lymphoid tissue (LDALT) has a dense supply with lymphatics.
CONCLUSIONS
NALT and LDALT play a key role in the immune system of the mouse head, where they function as primary recognition sites for antigens. Using the dense lymphatic networks along the NLD described in this study, these antigens reach lymphatics near the palatine and are further drained to lymph nodes of the head and neck region. NALT and LDALT develop in immediate vicinity of lymphatic vessels. Therefore, we suggest a causative connection of lymphatic vessels and the development of lymphoid tissues.
Topics: Animals; Humans; Immunity, Mucosal; Lacrimal Apparatus; Lymph Nodes; Lymphatic Vessels; Lymphoid Tissue; Mice, Inbred Strains; Nasal Mucosa; Nasolacrimal Duct
PubMed: 29368640
DOI: 10.1186/s12865-018-0242-3 -
Nature Reviews. Immunology Jun 2015Over the past decade, a series of discoveries relating to fibroblastic reticular cells (FRCs) — immunologically specialized myofibroblasts found in lymphoid tissue —... (Review)
Review
Over the past decade, a series of discoveries relating to fibroblastic reticular cells (FRCs) — immunologically specialized myofibroblasts found in lymphoid tissue — has promoted these cells from benign bystanders to major players in the immune response. In this Review, we focus on recent advances regarding the immunobiology of lymph node-derived FRCs, presenting an updated view of crucial checkpoints during their development and their dynamic control of lymph node expansion and contraction during infection. We highlight the robust effects of FRCs on systemic B cell and T cell responses, and we present an emerging view of FRCs as drivers of pathology following acute and chronic viral infections. Lastly, we review emerging therapeutic advances that harness the immunoregulatory properties of FRCs.
Topics: Animals; B-Lymphocytes; Cell Communication; Cell Movement; Cell Proliferation; Dendritic Cells, Follicular; Humans; Immune Tolerance; Infections; Lymph Nodes; Lymphoid Tissue; Models, Immunological; Myofibroblasts; T-Lymphocytes; Virus Diseases
PubMed: 25998961
DOI: 10.1038/nri3846 -
Microcirculation (New York, N.Y. : 1994) Oct 2016The intrinsic lymphatic pump is critical to proper lymph transport and is impaired in models of the MetSyn. Lymphatic contractile inhibition under inflammatory...
OBJECTIVE
The intrinsic lymphatic pump is critical to proper lymph transport and is impaired in models of the MetSyn. Lymphatic contractile inhibition under inflammatory conditions has been linked with elevated NO production by activated myeloid-derived cells. Hence we hypothesized that inhibition of the MLV pump function in MetSyn animals was dependent on NO and was associated with altered macrophage recruitment and polarization within the MLV.
METHODS
We used a high fructose-fed rat model of MetSyn. Macrophage polarization was determined by whole mount immunofluorescence in mesenteric neurovascular bundles based on expression of CD163, CD206, and MHCII. We also utilized isolated vessel isobaric preparations to determine the role for elevated NO production in the inhibition of MLV contractility. Both LECs and LMCs were used to assess the cytokines and chemokines to test how the lymphatic cells response to inflammatory conditions.
RESULTS
Data demonstrated a greater accumulation of M1-skewed (CD163 MHCII ) macrophages that were observed both within the perivascular adipose tissue and invested along the lymphatic vessels in MetSyn rats when compared to control rats. LECs and LMCs basally express the macrophage maturation polarization cytokines monocyte colony-stimulating factor and dramatically up regulate the M1 promoting cytokine granulocyte/monocyte colony-stimulating factor in response to lipopolysaccharide stimulation. MetSyn MLVs exhibited altered phasic contraction frequency. Incubation of MetSyn MLVs with LNAME or Glib had a partial restoration of lymphatic contraction frequency.
CONCLUSION
The data presented here provide the first evidence for a correlation between alterations in macrophage status and lymphatic dysfunction that is partially mediated by NO and K channel in MetSyn rats.
Topics: Animals; Antigens, CD; Antigens, Differentiation, Myelomonocytic; Chemokines; Cytokines; Histocompatibility Antigens Class II; Immunophenotyping; Lectins, C-Type; Lymphatic Vessels; Lymphoid Tissue; Macrophages; Male; Mannose Receptor; Mannose-Binding Lectins; Mesentery; Metabolic Syndrome; Muscle Contraction; Nitric Oxide; Rats; Rats, Sprague-Dawley; Receptors, Cell Surface
PubMed: 27588380
DOI: 10.1111/micc.12307 -
Toxicologic Pathology 2006The secretory epithelial surfaces of the body are a major route of entry for potentially pathogenic substances. The organized mucosal lymphoid tissues that are found... (Review)
Review
The secretory epithelial surfaces of the body are a major route of entry for potentially pathogenic substances. The organized mucosal lymphoid tissues that are found within the gastrointestinal and respiratory tracts are therefore particularly important as a first line of defense against harmful compounds. The major function of these mucosa-associated lymphoid tissues (MALT) is to initiate local IgA immune responses, which are then passed on to draining lymph nodes. For enhanced histopathology, the separate compartments of each lymphoid tissue should be evaluated separately for changes in size and lymphocyte cellularity and descriptive rather than interpretive terminology should be used to characterize any changes. The organization of MALT is similar to that of lymph nodes with B-cell-rich follicles and T-cell-rich interfollicular areas. Therefore, these two compartments should be evaluated separately for changes in size and lymphocyte cellularity and the germinal center development within lymphoid follicles should be evaluated as well.
Topics: Animals; Histological Techniques; Immunotoxins; Lymphoid Tissue; Mice; Mucous Membrane; Rats
PubMed: 17067953
DOI: 10.1080/01926230600939989 -
Veterinary Research 2006For maintenance of immunity and tolerance, the organs and tissues of the organism are connected by migrating lymphoid cells. Understanding lymphocyte migration is... (Review)
Review
For maintenance of immunity and tolerance, the organs and tissues of the organism are connected by migrating lymphoid cells. Understanding lymphocyte migration is essential for many disorders and diseases-- especially in the mucosa-lined organs. Detailed analyses of migrating lymphocytes have been performed in many species, especially in laboratory animals. However, important experiments in lymphocyte migration have been carried out in large animals, for example sheep, cattle and pigs. These species allow experimental procedures like in situ-organ labelling, lymphocyte retransfusion studies or lymph vessel cannulations. Such studies have made an important contribution to the understanding of the overall principles of lymphocyte migration especially in the mucosal immune system. Major results on the specific migration of naïve and memory T cells through lymphoid organs, the re-distribution of gamma/delta T cells in the intestinal immune system and the emigration of newly produced B cells from the ileal Peyer's patches have been obtained in large animals. Since there are growing numbers of markers for large animals, and molecular biology methods are available in these species, experiments in large animals will be an essential tool for the understanding of lymphocyte migration especially in mucosal organs.
Topics: Animals; Cell Movement; Lymphocytes; Lymphoid Tissue; Mucous Membrane
PubMed: 16611551
DOI: 10.1051/vetres:2006004 -
The Biochemical Journal Nov 1988Afferent lymph vessels entering popliteal lymph nodes of sheep were infused with [3H]acetyl-labelled hyaluronan of high Mr (4.3 x 10(6)-5.5 x 10(6)) and low Mr (1.5 x...
Afferent lymph vessels entering popliteal lymph nodes of sheep were infused with [3H]acetyl-labelled hyaluronan of high Mr (4.3 x 10(6)-5.5 x 10(6)) and low Mr (1.5 x 10(5)). Analysis of efferent lymph and of residues in the nodes showed that hyaluronan presented by this route is taken up and degraded by lymphatic tissue. Labelled residues isolated in node extracts by gel chromatography and h.p.l.c. included N-acetylglucosamine, acetate, water and a fraction provisionally identified as N-acetylglucosamine 6-phosphate. Between 48 and 75% of the infused material was unrecovered, and had been presumably eliminated through the bloodstream as diffusible residues. Rates of degradation reached as high as 43 micrograms/h in a node of 2 g wt. infused with 56 micrograms/h. Some HA passed into efferent lymph and some was detected in the nodes, but fractions of Mr greater than 1 x 10(6) were not found in either. It is concluded that the amounts and Mr values of hyaluronan released from the tissues into peripheral lymph can be significantly underestimated by analysis of efferent lymph, i.e. lymph that has passed through lymph nodes. A substantial role in the normal metabolic turnover of at least one major constituent of intercellular matrix and connective tissue may now be added to the established functions of the lymphatic system.
Topics: Adsorption; Animals; Chromatography, Gel; Chromatography, High Pressure Liquid; Female; Hyaluronic Acid; Lymph; Lymph Nodes; Lymphoid Tissue; Molecular Weight; Polyvinyls; Sheep; Tritium
PubMed: 3223897
DOI: 10.1042/bj2560153 -
Toxicologic Pathology Apr 2012The immune and hematopoietic systems play an important role in the normal homeostasis of blood and blood cells and for immune responses to endogenous and exogenous... (Review)
Review
The immune and hematopoietic systems play an important role in the normal homeostasis of blood and blood cells and for immune responses to endogenous and exogenous processes and insults. In order to interpret histopathologic changes in the immune and hematopoietic systems, it is important to understand the normal anatomy and histology of the thymus, spleen, lymph nodes, bone marrow, and other tissues. The thymus, spleen, and lymph nodes can be categorized by anatomical compartments, each of which contributes to specific immune functions. Lesions may be diagnosed by interpretive or descriptive (semiquantitative) methods. The interpretation of these tissues by lesion in anatomical compartments should allow for better understanding of these reactions and more definitive pathologic findings. Proliferative lesions may be difficult to differentiate from lymphomas and leukemias. The use of immunohistochemistry, compartmental pathology, and methods for the evaluation of clonality will make interpretation easier.
Topics: Animals; Hematopoietic System; Humans; Hyperplasia; Lymphoid Tissue; Lymphoproliferative Disorders; Mice; Rats
PubMed: 22215512
DOI: 10.1177/0192623311431467 -
The Journal of Antimicrobial... Sep 2021Multiple tissue reservoirs are established soon after HIV infection, and some tissues may also be pharmacological sanctuaries. Parenteral administration of...
BACKGROUND
Multiple tissue reservoirs are established soon after HIV infection, and some tissues may also be pharmacological sanctuaries. Parenteral administration of antiretroviral (ARV) drugs for treatment and prevention of HIV infection is an active area of drug development. The influence of route of administration on ARV tissue pharmacokinetics is not known.
OBJECTIVES
To investigate ARV pharmacokinetics in lymphatic and select non-lymphatic tissues (e.g. brain and testes) after intramuscular and subcutaneous administration compared with oral in BALB/c mice.
METHODS
Tissue concentrations of cobicistat, efavirenz, elvitegravir, maraviroc, rilpivirine, tenofovir alafenamide and tenofovir disoproxil fumarate were determined. The tissue penetration ratio (TPR) was the primary measure for comparison; a change in TPR arises from factors affecting tissue distribution controlling for changes in systemic bioavailability.
RESULTS
Intramuscular and subcutaneous delivery increased TPRs in the lymph node and spleen for 27 of 28 (96%) drug administration events. Decreased TPRs, however, were found in some tissues such as the brain and testes.
CONCLUSIONS
These results demonstrate a change in route of drug administration from oral to intramuscular or subcutaneous can change tissue uptake. This has implications for HIV pharmacotherapy. For example, HIV persists in lymphoid tissues despite long-term oral ARV therapy, and low ARV concentrations have been found in lymphoid tissues. The improved ARV lymphatic tissue bioavailability with intramuscular and subcutaneous administration allows future studies to investigate these routes of drug administration as a therapeutic manoeuvre to limit viral persistence and eliminate viral sanctuaries in the lymphatic tissues, which is a prerequisite for eradication of HIV.
Topics: Animals; Anti-HIV Agents; HIV Infections; Lymphoid Tissue; Mice; Mice, Inbred BALB C; Pharmaceutical Preparations
PubMed: 34312680
DOI: 10.1093/jac/dkab228 -
Mucosal Immunology Nov 2012While only partial immune reconstitution in gut-associated lymphoid tissue typically occurs following initiation of highly active antiretroviral therapy (HAART) in human... (Review)
Review
While only partial immune reconstitution in gut-associated lymphoid tissue typically occurs following initiation of highly active antiretroviral therapy (HAART) in human immunodeficiency virus (HIV) infection, near-complete immune reconstitution has occasionally been described. This review highlights findings from studies examining the effects of HAART and the timing of its initiation on gastrointestinal (GI) CD4+ T-cell recovery. Its effects on specific CD4+ T-cell subtypes, CD8+ T cells, natural killer cells, and immunoglobulins are also described. Finally, the ability of HAART to restore the intestinal epithelial barrier and lymphatic tissue architecture and reduce microbial translocation is addressed. Determining whether HAART has the ability to prevent permanent GI immune damage when commenced in acute HIV infection has implications for the optimal timing of HAART initiation.
Topics: Acute Disease; Anti-HIV Agents; Antiretroviral Therapy, Highly Active; CD4 Lymphocyte Count; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; HIV Infections; HIV-1; Humans; Immunity, Mucosal; Immunoglobulins; Intestinal Mucosa; Killer Cells, Natural; Lymphoid Tissue; Time Factors
PubMed: 22929559
DOI: 10.1038/mi.2012.82