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A Review of Classic Physiological Systems
Published in Len Wisneski, The Scientific Basis of Integrative Health, 2017
The lymphatic system, which includes the spleen, thymus, tonsils, and various lymph nodes, supports the immune system (see Figure 1.11). The lymphatic system filters and removes foreign particles. Lymph nodes store B and T lymphocytes for activation when an antigen is present. Lymph nodes are distributed throughout the body and filter the lymph before it is sent out into the blood circulation again. They can remove bacteria, viruses, and cancerous cells. There are other cells called macrophages that are also present in lymph nodes and contribute significantly to the immune response. Lymph is blood plasma that has filtered through capillary walls. It is called interstitial fluid until it enters the lymph capillaries, and then it is called lymph. There is a whole lymph flow system that is still somewhat enigmatic. For example, it has been believed that the brain was devoid of lymphatic vessels until the recent discovery of meningeal lymphatic vessels (Aspelund et al., 2015; Louveau et al., 2015). This discovery shattered the long-held belief that the CNS was restricted to communication with the systemic lymphatic system. This may have major implications regarding our understanding of immune-based CNS diseases such as multiple sclerosis and several others.
Microbiota-derived metabolites as drivers of gut–brain communication
Published in Gut Microbes, 2022
Hany Ahmed, Quentin Leyrolle, Ville Koistinen, Olli Kärkkäinen, Sophie Layé, Nathalie Delzenne, Kati Hanhineva
As circulating lymphocytes may infiltrate peripheral tissues, similarly the cytokines or activated immune cells can be transported to the CNS and modulate the immune homeostasis.199 While the BBB restricts the passage of immune cells but not cytokines, the lymphatic system is an alternative route facilitating migration of these cells and bacterial components from the periphery to the CNS.200 The meningeal lymphatic vessels reach the CNS, exchange the cerebrospinal fluid, and drain immune cells and small compounds from the brain toward the periphery. Direct supply of microbiota-derived molecules or activated immune cells could induce a central immune response, such as the activation of microglia and T cells.197 This in turn leads to the production of pro-inflammatory cytokines promoting neuroinflammation. Cytokines may also deteriorate BBB permeability that predisposes to increased passage of harmful compounds or metabolites from the circulation through the BBB.200 Moreover, peripheral administration of pro-inflammatory cytokines has been shown to induce sickness behavior characterized by depressive-like behavior and reduced appetite in rodents.199 However, the range of mechanisms describing microbially mediated crosstalk between peripheral and central immune responses are widely uncharacterized.
Deciphering Alzheimer’s disease: predicting new therapeutic strategies via improved understanding of biology and pathogenesis
Published in Expert Opinion on Therapeutic Targets, 2020
Rita Khoury, George T. Grossberg
Beyond the glymphatic system, Louveau and colleagues pointed to the existence of meningeal lymphatic vessels, and demonstrated their crucial role in immunosurveillance, drainage of macromolecules and immune cells, and CSF/ISF circulation [55,60]. ISF is hence thought to be conveyed to the cervical lymph nodes and the peripheral lymphatic system not only through the cribiform plate and the nasal lymphatics but also through meningeal lymphatics [61]. Any dysfunction in the cerebral lymphatic drainage system can lead to the accumulation of waste proteins and debris, leading to neurodegeneration. Experimental ligation of deep cervical nodes for instance led to an increase in the diameter of the meningeal lymphatic vessels similar to lymphedema that is observed in peripheral tissues [60]. A third component of the brain lymphatic drainage system involves perivascular pathways located along cerebral vascular basement membranes, responsible for removing ISF and wastes from the brain along the tunica media of cerebral arteries, toward the leptomeningeal arteries at the surface of the brain and eventually to the cervical lymphatics of the exterior
Dynamics of Evans blue clearance from cerebrospinal fluid into meningeal lymphatic vessels and deep cervical lymph nodes
Published in Neurological Research, 2018
Marcela Maloveska, Jan Danko, Eva Petrovova, Lenka Kresakova, Katarina Vdoviakova, Alena Michalicova, Andrej Kovac, Veronika Cubinkova, Dasa Cizkova
Recent discovery of meningeal lymphatic vessels has re-classified the long-held dogma that the CNS is fully depleted of lymphatic system, revealing an immune-privileged tissue to which immune cells have restricted access under normal physiological conditions [1,2]. The evidence of a lymphatic vascular system distribution in brain meninges of mice has been provided independently by two different groups [3,4]. The first group built the theory on its previous findings about lymph nature of Schlemm’s canal in the eye, another immune-privileged organ, and expected the incidence of similar lymphoid structures in the brain [5]. The second one confirmed the lymphatic character of vessels by assessing the presence of several specific lymphatic endothelial cell (LEC) markers, including PROX1, LYVE1, PDPN, VEGFR3 and by involving electron microscopy in the brain and dura mater [4]. Furthermore, they showed that the T, B cells and MHC class-II-expressing myeloid cells were localized inside newly discovered meningeal lymphatic vessels, confirming that they are capable of carrying immune cells [5]. According to these findings, the meningeal lymphatics were considered as a part of the lymphatic system, responsible for draining excess fluid, waste products and immune cells from the CNS into the corresponding lymph nodes [3–5].