The lymphatic system, or lymphoid system, is an organ system in vertebrates that is part of the immune system and complementary to the circulatory system. It consists of a large network of lymphatic vessels, lymph nodes, lymphoid organs, lymphatic tissue and lymph. Lymph is a clear fluid carried by the lymphatic vessels back to the heart for re-circulation. The Latin word for lymph, lympha, refers to the deity of fresh water, "Lympha".
Macrophages are a type of white blood cell of the innate immune system that engulf and digest pathogens, such as cancer cells, microbes, cellular debris and foreign substances, which do not have proteins that are specific to healthy body cells on their surface. This process is called phagocytosis, which acts to defend the host against infection and injury.
Immune tolerance, also known as immunological tolerance or immunotolerance, refers to the immune system's state of unresponsiveness to substances or tissues that would otherwise trigger an immune response. It arises from prior exposure to a specific antigen and contrasts the immune system's conventional role in eliminating foreign antigens. Depending on the site of induction, tolerance is categorized as either central tolerance, occurring in the thymus and bone marrow, or peripheral tolerance, taking place in other tissues and lymph nodes. Although the mechanisms establishing central and peripheral tolerance differ, their outcomes are analogous, ensuring immune system modulation.
Interleukin 19 (IL-19) is an immunosuppressive protein that belongs to the IL-10 cytokine subfamily.
Indoleamine-pyrrole 2,3-dioxygenase (IDO or INDO EC 1.13.11.52) is a heme-containing enzyme physiologically expressed in a number of tissues and cells, such as the small intestine, lungs, female genital tract or placenta. In humans is encoded by the IDO1 gene. IDO is involved in tryptophan metabolism. It is one of three enzymes that catalyze the first and rate-limiting step in the kynurenine pathway, the O2-dependent oxidation of L-tryptophan to N-formylkynurenine, the others being indolamine-2,3-dioxygenase 2 (IDO2) and tryptophan 2,3-dioxygenase (TDO). IDO is an important part of the immune system and plays a part in natural defense against various pathogens. It is produced by the cells in response to inflammation and has an immunosuppressive function because of its ability to limit T-cell function and engage mechanisms of immune tolerance. Emerging evidence suggests that IDO becomes activated during tumor development, helping malignant cells escape eradication by the immune system. Expression of IDO has been described in a number of types of cancer, such as acute myeloid leukemia, ovarian cancer or colorectal cancer. IDO is part of the malignant transformation process and plays a key role in suppressing the anti-tumor immune response in the body, so inhibiting it could increase the effect of chemotherapy as well as other immunotherapeutic protocols. Furthermore, there is data implicating a role for IDO1 in the modulation of vascular tone in conditions of inflammation via a novel pathway involving singlet oxygen.
G protein coupled receptor 132, also termed G2A, is classified as a member of the proton sensing G protein coupled receptor (GPR) subfamily. Like other members of this subfamily, i.e. GPR4, GPR68 (OGR1), and GPR65 (TDAG8), G2A is a G protein coupled receptor that resides in the cell surface membrane, senses changes in extracellular pH, and can alter cellular function as a consequence of these changes. Subsequently, G2A was suggested to be a receptor for lysophosphatidylcholine (LPC). However, the roles of G2A as a pH-sensor or LPC receptor are disputed. Rather, current studies suggest that it is a receptor for certain metabolites of the polyunsaturated fatty acid, linoleic acid.
Hydroxycarboxylic acid receptor 2 (HCA2), also known as GPR109A and niacin receptor 1 (NIACR1), is a protein which in humans is encoded (its formation is directed) by the HCAR2 gene and in rodents by the Hcar2 gene. The human HCAR2 gene is located on the long (i.e., "q") arm of chromosome 12 at position 24.31 (notated as 12q24.31). Like the two other hydroxycarboxylic acid receptors, HCA1 and HCA3, HCA2 is a G protein-coupled receptor (GPCR) located on the surface membrane of cells. HCA2 binds and thereby is activated by D-β-hydroxybutyric acid (hereafter termed β-hydroxybutyric acid), butyric acid, and niacin (also known as nicotinic acid). β-Hydroxybutyric and butyric acids are regarded as the endogenous agents that activate HCA2. Under normal conditions, niacin's blood levels are too low to do so: it is given as a drug in high doses in order to reach levels that activate HCA2.
Giant-cell carcinoma of the lung (GCCL) is a rare histological form of large-cell lung carcinoma, a subtype of undifferentiated lung cancer, traditionally classified within the non-small-cell lung carcinomas (NSCLC).
Tumor-associated macrophages (TAMs) are a class of immune cells present in high numbers in the microenvironment of solid tumors. They are heavily involved in cancer-related inflammation. Macrophages are known to originate from bone marrow-derived blood monocytes or yolk sac progenitors, but the exact origin of TAMs in human tumors remains to be elucidated. The composition of monocyte-derived macrophages and tissue-resident macrophages in the tumor microenvironment depends on the tumor type, stage, size, and location, thus it has been proposed that TAM identity and heterogeneity is the outcome of interactions between tumor-derived, tissue-specific, and developmental signals.
Adipose tissue macrophages (ATMs) comprise resident macrophages present in adipose tissue. Besides adipocytes, adipose tissue contains the stromal vascular fraction (SVF) of cells that includes pre-adipocytes, fibroblasts, vascular endothelial cells, and a large variety of immune cells. The latter ones are composed of mast cells, eosinophils, B cells, T cells and macrophages. The number of macrophages within adipose tissue differs depending on the metabolic status. As discovered by Rudolph Leibel and Anthony Ferrante et al. in 2003 at Columbia University, the percentage of macrophages within adipose tissue ranges from 10% in lean mice and humans up to 50% in obese leptin deficient mice, and up to 40% in obese humans. ATMs comprise nearly 50% of all immune cells in normal conditions, suggesting an important role in supporting normal functioning of the adipose tissue. Increased number of adipose tissue macrophages may correlate with increased production of pro-inflammatory molecules and might therefore contribute to the pathophysiological consequences of obesity, although is becoming recognized that in healthy conditions tissue-resident macrophages actively support a variety of critical physiological functions in nearly all organs and tissues, including adipose tissue.
The tumor microenvironment is a complex ecosystem surrounding a tumor, composed of cancer cells, stromal tissue and the extracellular matrix. Mutual interaction between cancer cells and the different components of the tumor microenvironment support its growth and invasion in healthy tissues which correlates with tumor resistance to current treatments and poor prognosis. The tumor microenvironment is in constant change because of the tumor's ability to influence the microenvironment by releasing extracellular signals, promoting tumor angiogenesis and inducing peripheral immune tolerance, while the immune cells in the microenvironment can affect the growth and evolution of cancerous cells.
Myeloid-derived suppressor cells (MDSC) are a heterogeneous group of immune cells from the myeloid lineage.
Neuroinflammation is inflammation of the nervous tissue. It may be initiated in response to a variety of cues, including infection, traumatic brain injury, toxic metabolites, or autoimmunity. In the central nervous system (CNS), including the brain and spinal cord, microglia are the resident innate immune cells that are activated in response to these cues. The CNS is typically an immunologically privileged site because peripheral immune cells are generally blocked by the blood–brain barrier (BBB), a specialized structure composed of astrocytes and endothelial cells. However, circulating peripheral immune cells may surpass a compromised BBB and encounter neurons and glial cells expressing major histocompatibility complex molecules, perpetuating the immune response. Although the response is initiated to protect the central nervous system from the infectious agent, the effect may be toxic and widespread inflammation as well as further migration of leukocytes through the blood–brain barrier may occur.
Immunoediting is a dynamic process that consists of immunosurveillance and tumor progression. It describes the relation between the tumor cells and the immune system. It is made up of three phases: elimination, equilibrium, and escape.
Tissue-resident memory T cells or TRM cells represent a subset of a long-lived memory T cells that occupies epithelial, mucosal and other tissues without recirculating. TRM cells are transcriptionally, phenotypically and functionally distinct from central memory (TCM) and effector memory (TEM) T cells which recirculate between blood, the T cell zones of secondary lymphoid organ, lymph and nonlymphoid tissues. Moreover, TRM cells consist of diverse populations both between tissues and within a single tissue. TRM cells provide protection against infection in extralymphoid tissues.
Epstein–Barr virus–associated lymphoproliferative diseases are a group of disorders in which one or more types of lymphoid cells, i.e. B cells, T cells, NK cells, and histiocytic-dendritic cells, are infected with the Epstein–Barr virus (EBV). This causes the infected cells to divide excessively, and is associated with the development of various non-cancerous, pre-cancerous, and cancerous lymphoproliferative disorders (LPDs). These LPDs include the well-known disorder occurring during the initial infection with the EBV, infectious mononucleosis, and the large number of subsequent disorders that may occur thereafter. The virus is usually involved in the development and/or progression of these LPDs although in some cases it may be an "innocent" bystander, i.e. present in, but not contributing to, the disease.
T-cell/histiocyte-rich large B-cell lymphoma (THRLBCL) is a malignancy of B cells. B-cells are lymphocytes that normally function in the humoral immunity component of the adaptive immune system by secreting antibodies that, for example, bind to and neutralize invasive pathogens. Among the various forms of B-cell lymphomas, THRLBCL is a rarely occurring subtype of the diffuse large B-cell lymphomas (DLBCL). DLBCL are a large group of lymphomas that account for ~25% of all non-Hodgkin lymphomas worldwide. THRLBCL is distinguished from the other DLBCL subtypes by the predominance of non-malignant T-cell lymphocytes and histiocytes over malignant B-cells in its tumors and tissue infiltrates.
Th22 cells are subpopulation of CD4+ T cells that produce interleukin-22 (IL-22). They play a role in the protective mechanisms against variety of bacterial pathogens, tissue repair and wound healing, and also in pathologic processes, including inflammations, autoimmunity, tumors, and digestive organs damages.
Cellular adoptive immunotherapy is a type of immunotherapy. Immune cells such as T-cells are usually isolated from patients for expansion or engineering purposes and reinfused back into patients to fight diseases using their own immune system. A major application of cellular adoptive therapy is cancer treatment, as the immune system plays a vital role in the development and growth of cancer. The primary types of cellular adoptive immunotherapies are T cell therapies. Other therapies include CAR-T therapy, CAR-NK therapy, macrophage-based immunotherapy and dendritic cell therapy.
Apoptosis inhibitor of macrophage (AIM) is a protein produced by macrophages that regulates immune responses and inflammation. It plays a crucial role in key intracellular processes like lipid metabolism and apoptosis.
