Gene set analysis suggested up-regulation of a variety of pr......
Gene set analysis suggested up-regulation of a variety of pro- and anti-inflammatory cytokines, including interleukin 1alpha (IL-1alpha), IL-2, IL-3, IL-5, IL-8, IL-9, IL-10, IL-12A, IL-13, IL-15, IL-18, interferon gamma (IFNgamma), and lymphotoxin alpha (TNF superfamily member 1).More...
Positive relationships between IL2 and other components at different levels (count: 0)
Positive relationship network of IL2 in MK4MDD
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Genetic/Epigenetic Locus
Protein and Other Molecule
Cell and Molecular Pathway
Neural System
Cognition and Behavior
Symptoms and Signs
Environment
MDD
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Negative relationships between IL2 and MDD (count: 0)
Negative relationships between IL2 and other components at different levels (count: 0)
Graft-versus-host disease (GVHD) pathophysiology can be summ......
Graft-versus-host disease (GVHD) pathophysiology can be summerized in a three-step process. During step 1, the conditioning regimen (irradiation and/or chemotherapy) leads to damage, activation of host tissues and induction of inflammatory cytokines secretion. Increased expression of major histocompatibility complex (MHC) antigens and adhesion molecules leads to enhancement of the recognition of host MHC and/or minor histocompatibility antigens by mature donor T cells. Donor T-cell activation in step II is characterized by the predominance of Th1 cells and the secretion of IL-2 and IFN-gamma. These cytokines induce further T-cell expansion, induce cytotoxic T lymphocytes (CTL) and natural killer (NK) cells responses and prime additional mononuclear phagocytes to produce TNF-alpha and IL-1. Also, nitric oxide (NO) is produced by activated macrophages, and it may contribute to the tissue damage seen during step 3. Lipopolysaccharide (LPS), which leaks through the intestinal mucosa that was damaged during step 1, together with IFN-gamma, from step 2, further stimulate macrophages to secrete cytokines and NO. During step 3, the effector phase, activated CTL and NK cells mediate cytotoxicity against target host cells through Fas-Fas ligand interactions and perforin-granzyme B.More...
Type I diabetes mellitus is a disease that results from auto......
Type I diabetes mellitus is a disease that results from autoimmune destruction of the insulin-producing beta-cells. Certain beta-cell proteins act as autoantigens after being processed by antigen-presenting cell (APC), such as macrophages and dendritic cells, and presented in a complex with MHC-II molecules on the surface of the APC. Then immunogenic signals from APC activate CD4+ T cells, predominantly of the Th1 subset. Antigen-activated Th1 cells produce IL-2 and IFNgamma. They activate macrophages and cytotoxic CD8+ T cells, and these effector cells may kill islet beta-cells by one or both of two types of mechanisms: (1) direct interactions of antigen-specific cytotoxic T cells with a beta-cell autoantigen-MHC-I complex on the beta-cell, and (2) non-specific inflammatory mediators, such as free radicals/oxidants and cytokines (IL-1, TNFalpha, TNFbeta, IFNgamma). Type I diabetes is a polygenic disease. One of the principle determining genetic factors in diabetes incidence is the inheritance of mutant MHC-II alleles. Another plausible candidate gene is the insulin gene.More...
The classification of autoimmune throid disease (AITD) inclu......
The classification of autoimmune throid disease (AITD) includes Hashimoto's thyroiditis (HT) or chronic autoimmune thyroiditis and its variants, Graves' disease (GD) and autoimmune atrophic thyroiditis or primary myxedema. HT is characterized by the presence of goitre, thyroid autoantibodies against thyroid peroxidase (TPO) and thyroglobulin (Tg) in serum and varying degrees of thyroid dysfunction. During HT, self-reactive CD4+ T lymphocytes (Th) recruit B cells and CD8+ T cells (CTL) into the thyroid. Disease progression leads to the death of thyroid cells and hypothyroidism. Both autoantibodies and thyroid-specific cytotoxic T lymphocytes (CTLs) have been proposed to be responsible for autoimmune thyrocyte depletion. In GD, the TSH-R is the most important autoantigen. Antibodies directed against it mimic the effects of the hormone on thyroid cells, TSH, stimulating autonomous production of thyroxine and triiodothyronine and causing hyperthyroidism. The presence of TSH-R-blocking antibodies that bind the TSH receptor in a similar fashion to the antibodies in patients with Graves' disease but that block rather than activate the receptor explains some cases of atrophic hypothyroidism.More...
After transplantation of organ allografts, there are two pat......
After transplantation of organ allografts, there are two pathways of antigen presentation. In the direct pathway, recipient T cells react to intact allogeneic MHC molecules expressed on the surface of donor cells. This pathway would activate host CD4 or CD8 T cells. In contrast, donor MHC molecules (and all other proteins) shed from the graft can be taken up by host APCs and presented to recipient T cells in the context of self-MHC molecules - the indirect pathway. Such presentation activates predominantly CD4 T cells. A direct cytotoxic T-cell attack on graft cells can be made only by T cells that recognize the graft MHC molecules directly. Nontheless, T cells with indirect allospecificity can contribute to graft rejection by activating macrophages, which cause tissue injury and fibrosis, and are also likely to be important in the development of an alloantibody response to graft.More...
The intestine is the largest lymphoid tissue in the body. On......
The intestine is the largest lymphoid tissue in the body. One striking feature of intestinal immunity is its ability to generate great amounts of noninflammatory immunoglobulin A (IgA) antibodies that serve as the first line of defense against microorganisms. The basic map of IgA production includes induction of mucosal B cells in the Peyer's patches, circulation through the bloodstream and homing to intestinal mucosa of IgA-commited plasma cells, and local antibody production for export across the intestinal membranes. Multiple cytokines, including TGF-{beta}, IL-10, IL-4, IL-5, and IL-6, are required to promote IgA class switching and terminal differentiation process of the B cells. Secreted IgA promotes immune exclusion by entrapping dietary antigens and microorganisms in the mucus and functions for neutralization of toxins and pathogenic microbes.More...
The Janus kinase/signal transducers and activators of transc......
The Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway is one of a handful of pleiotropic cascades used to transduce a multitude of signals for development and homeostasis in animals, from humans to flies. In mammals, the JAK/STAT pathway is the principal signaling mechanism for a wide array of cytokines and growth factors. Following the binding of cytokines to their cognate receptor, STATs are activated by members of the JAK family of tyrosine kinases. Once activated, they dimerize and translocate to the nucleus and modulate the expression of target genes. In addition to the activation of STATs, JAKs mediate the recruitment of other molecules such as the MAP kinases, PI3 kinase etc. These molecules process downstream signals via the Ras-Raf-MAP kinase and PI3 kinase pathways which results in the activation of additional transcription factors.More...
Activation of T lymphocytes is a key event for an efficient ......
Activation of T lymphocytes is a key event for an efficient response of the immune system. It requires the involvement of the T-cell receptor (TCR) as well as costimulatory molecules such as CD28. Engagement of these receptors through the interaction with a foreign antigen associated with major histocompatibility complex molecules and CD28 counter-receptors B7.1/B7.2, respectively, results in a series of signaling cascades. These cascades comprise an array of protein-tyrosine kinases, phosphatases, GTP-binding proteins and adaptor proteins that regulate generic and specialised functions, leading to T-cell proliferation, cytokine production and differentiation into effector cells.More...
Cytokines are soluble extracellular proteins or glycoprotein......
Cytokines are soluble extracellular proteins or glycoproteins that are crucial intercellular regulators and mobilizers of cells engaged in innate as well as adaptive inflammatory host defenses, cell growth, differentiation, cell death, angiogenesis, and development and repair processes aimed at the restoration of homeostasis. Cytokines are released by various cells in the body, usually in response to an activating stimulus, and they induce responses through binding to specific receptors on the cell surface of target cells. Cytokines can be grouped by structure into different families and their receptors can likewise be grouped.More...
The Co-Stimulatory Signal During T-cell Activation
For a T cell to be activated by a specific antigen, the T ce......
For a T cell to be activated by a specific antigen, the T cell receptor must recognize complexes of MHCI with the antigen on the surface of an antigen-presenting cell. T cells and the T cell receptor complex do not respond to antigen in solution, but even for the specific antigen they only respond to antigen-MHC-1 complexes on the cell surface. This interaction is necessary for T cell activation, but it is not sufficient. T cell activation also requires a co-stimulatory signal involving interaction of CD28 on the T cell with CD80 or CD86 (B7 family genes) on the antigen-presenting cell. CD28 activates a signal transduction pathway acting through PI-3K, Lck and Grb-2/ITK to provide its co-stimulatory signal for T cell activation. Another means to control T cell activation is by expressing factors that down-regulate T cell activation. Signaling by activated T cell receptors induces expression of CTLA-4, a receptor that opposes T cell activation. CTLA-4 has a higher affinity than CD28 for B7 proteins, terminating T cell activation. ICOS is a protein related to CD28 that is only expressed on activated T cells, and that provides another important co-stimulatory signal. The requirement for co-stimulatory signals provides additional control mechanisms that prevent inappropriate and hazardous T cell activation.More...
Inflammation is a protective response to infection by the im......
Inflammation is a protective response to infection by the immune system that requires communication between different classes of immune cells to coordinate their actions. Acute inflammation is an important part of the immune response, but chronic inappropriate inflammation can lead to destruction of tissues in autoimmune disorders and perhaps neurodegenerative or cardiovascular disease. Secreted cytokine proteins provide signals between immune cells to coordinate the inflammatory response. Some cytokines such as IL-1, IL-6 and TNF act to broadly provoke the inflammatory response while others act on specific types of immune cells. Macrophages and other phagocytotic cells provide a front-line defense against bacterial infection. Macrophages stimulate the inflammatory responses of neutrophils, fibroblasts, and endothelial cells in response infection by secreting IL-1 and TNF. IL-1 and TNF cause fever through alteration of the body temperature set-point in the hypothalamus. Fibroblasts and endothelial cells respond to IL-1 and TNF by recruiting more immune cells to the site of inflammation. Secreted IL-8 is a chemokine that attracts neutrophils to sites of infection. Macrophages also present antigen to T helper cells that play a central role in coordinating immune responses. T helper cells induce clonal expansion of T cells that respond to antigen, with IL-2 as a key mediator of T cell proliferation and activation. TGF-beta is a negative regulator of proliferation in many cells, have anti-inflammatory actions in some settings. The cytotoxic activity of Natural Killer cells (NK cells) and lymphokine activated killer cells (LAK cells) toward viral infected or tumor cells is stimulated by IL-2 and other cytokines. T helpers secrete IL-3 and IL-5 to stimulate eosinophil proliferation and activation. Eosinophils are involved in the immune response to parasitic infection. T helper cells are required to stimulate B cell responses as well, with the cytokines IL-10, IL-4 and other cytokines regulating the clonal selection and differentiation of antigen-specific B cells to form antibody-secreting plasma B cells and memory cells. In addition to inducing activation and proliferation of specific differentiated immune cells, cytokines act on hematopoeitic stem cells, causing their proliferation and differentiation into the full range of immune cells.More...
Selective expression of chemokine receptors during T-cell polarization
Chemokine receptors expressed by T helper cells help recruit......
Chemokine receptors expressed by T helper cells help recruit cells to specific locations based on their chemoattractant ligands. The polarization of T cells into Th1 and Th2 cells is associated with their expression of different subsets of chemokine receptors. Naive CD4 positive cells that have not been exposed to antigen express CXCR4 and CCR7. The most abundant chemokine receptors on Th1 cells involved in the cellular immune response to microbial agents include CXCR3, CCR1, CCR2 and CCR5, while Th2 cells express CCR2, CCR3 and CCR5. An additional class of T cells termed semi-nave cells may be induced by TGF-beta to express yet another class of chemokine receptors, CCR4 and CCR7. Although the expression of chemokine receptors in different cells is preferred in these cases, it is not absolute or exclusive, and there is overlap in expression between Th1 and Th2 cells. Although CCR7 positive cells have been reported to lack effector action, not be polarized, and to home only to lymphoid tissues, other studies have found CCR7 positive Th1 and Th2 cells and have identified CCR7 positive cells in non-lymphoid tissues. CCR4 appears associated with homing of lymphocytes to the skin, and CCR9 is associated with homing to the small intestine, while other chemokines like CXCR3 and CCR5 are associated with homing toward inflamed tissues more broadly. The expression of different chemokine receptors by subsets of T helper cells plays an important role in the migration and homing of these cells in tissues, and targeting of the immune response to specific cells.More...
Regulation of T cell activation is a crucial component of ba......
Regulation of T cell activation is a crucial component of balanced functioning of the immune system. If the T cell response is too great and activation of self-responsive cells or unstimulated cells is not suppressed, then autoimmune disorders or tissue injury can result. Unstimulated T cells are maintained in a quiescent state and the activity of self-reactive T cells is maintained in an anergic state in which IL-2 expression is repressed. IL-2 is a cytokine with a key role in the activation and proliferation of T cells. The maintenance of T cells in the anergic or unstimulated state may not involve just an absence of activation, but an active repression of IL-2 expression, T cell proliferation and activation. TGF beta may play a role in suppressing T cell activation. Tob is a factor identified recently that represses T cell activation that is a member of a family of genes with anti-proliferative properties. Tob expression is highest in unstimulated and anergic T cells, and is reduced in activated T cells. Tob interacts with the TGF activated transcription factors SMAD2 and SMAD4, increasing their binding to the IL-2 promoter, and helping to repress IL-2 expression. This role of Tob suggests that interference in Tobs function may lead to autoimmune disease.More...
A key part of the immune system is the production of immunog......
A key part of the immune system is the production of immunoglobulins (antibodies) by B cells to bind and inactivate specific foreign antigens. The body produces B cells with a wide range of antigen specificities in the immunoglobulin B cell receptor, one antigen specificity per cell. When the B cell receptor immunoglobulin binds antigen, that cell is activated to proliferate and create plasma cells secreting immunoglobulins to bind that specific antigen. B cell activation also creates memory cells with the same antigen specificity that do not actively secrete immunoglobulin but provide for rapid future immune responses to the same antigen. B cells are not activated by antigen on their own, but require interaction with helper CD4+ T cells to become activated and proliferate. The B cell first expresses immunoglobulin on the cell surface as the B cell receptor. If the B cell receptor immunoglobulin binds specific antigen, then the cell internalizes the antigen and presents it to T cells in MHC II, where it is recognized by the T cell receptor. In addition to the interaction between the T cell receptor and the B cell MHC-antigen, T cell interaction with the B cell involves additional positive and negative regulatory signals. CD40 interaction with CD40L and CD28 interaction with CD80 provide positive costimulatory signals that stimulate B cell activation and proliferation. T cell receptor activation induces expression of molecules like the CD40 ligand that modulate the B cell-T cell interaction. The CD40-CD40L interaction induces cytokine production and expression of other genes and alters the fate of the B cell involved in the interaction. If the interaction between CD40 and CD40L is prolonged, the B cell can be induced to become a memory cell rather than a plasma cell. Fas ligand binding to Fas between B and T cells may negatively modulate B cell activation, inducing apoptosis that limits B cell proliferation and activation. Cytokines like IL-2, IL-4 and IL-10 also play an important role in B cell activation.More...
Several different cell types coordinate their efforts as par......
Several different cell types coordinate their efforts as part of the immune system, including B cells, T cells, macrophages, neutrophils, basophils and eosinophils. Each of these cell types has a distinct role in the immune system, and communicates with other immune cells using secreted factors called cytokines, including interleukins, TNF, and the interferons. Macrophages phagocytose foreign bodies and are antigen-presenting cells, using cytokines to stimulate specific antigen dependent responses by B and T cells and non-specific responses by other cell types. T cells secrete a variety of factors to coordinate and stimulate immune responses to specific antigen, such as the role of helper T cells in B cell activation in response to antigen. The proliferation and activation of eosinophils, neutrophils and basophils respond to cytokines as well. Cytokine communication is often local, within a tissue or between cells in close proximity. Each of the cytokines is secreted by one set of cells and provokes a response in another target set of cells, often including the cell that secretes the cytokine. Some cytokines, like IL-1, interferons and TNF, stimulate a broad inflammatory response in response to infection or injury. Other cytokines have more specific functions such the following examples. IL-2 stimulates the proliferation and activation of B and T cells. IL-4 plays a role in the differentiation of Th2 cells, in allergic responses, and in the switching of antibody types. IL-5 stimulates the production and maturation of eosinophils during inflammation. IL-8 is a chemokine, a chemotactic factor that attracts neutrophils, basophils and T cells to sites of inflammation. IL-12 and IL-18 are involved in helper T cell differentiation. IL-10 apparently acts to repress secretion of proinflammatory cytokines. The complex interplay of these different cytokine functions with immune cells is essential for correct immune function.More...
Helper T cells are found in two distinct cell types, Th1 and......
Helper T cells are found in two distinct cell types, Th1 and Th2, distinguished by the cytokines they produce and respond to and the immune responses they are involved in. Th1 cells produce pro-inflammatory cytokines like IFN-g, TNF-b and IL-2, while Th2 cells produce the cytokines IL-4, IL-5, IL-6 and IL-13. The cytokines produced by Th1 cells stimulate the phagocytosis and destruction of microbial pathogens while Th2 cytokines like IL-4 generally stimulate the production of antibodies directed toward large extracellular parasites. IL-5 stimulates eosinophil responses, also part of the immune response toward large extracellular parasites Th1 and Th2 are produced by differentiation from a non-antigen exposed precursor cell type, Thp. Exposure of Thp cells to antigen by antigen-presenting cells may result in their differentiation to Th0 cells, not yet committed to become either Th1 or Th2 cells, although the existence of Th0 cells is controversial. Cells committed as either Th1 and Th2 cells are called polarized, whether they are effector cells actively secreting cytokines or are memory cells. The stimulation of Thp cells by exposure to antigen-presenting cells induces the proliferation of undifferentiated cells, and their expression of IL-2 and IL-2 receptor. The differentiation of Th1 cells and Th2 cells depends on the cytokines they are exposed to. IL-12 causes Th1 differentiation and blocks Th2 cell production , while IL-4 causes Th2 differentiation and antagonizes Th1 development. IL-18 also induces Th1 differentiation. Polarized Th1 and Th2 cells also express distinct sets of chemokine receptors that further modify their homing and other cellular responses. Improved understanding of Th1 and Th2 differentiation will improve our overall understanding of the immune system, its response to infection and aberrant responses that lead to disease.More...
The activation of T cells requires a co-stimulatory signal w......
The activation of T cells requires a co-stimulatory signal with T cell receptor activation, provided in many cases by activation of CD28 in resting T cells. 4-1BB (CD137) is a member of the TNF receptor gene family that provides another T cell co-stimulatory signal. 4-1BB is expressed by activated cytotoxic and helper T cells and its expression is induced by a variety of T cell stimuli, including activation of the T cell receptor or stimulation with mitogens. The ligand for 4-1BB (4-1BBL) is induced on activated antigen-presenting cells including macrophages, activating T cells expressing 4-1BB. Mice lacking 4-1BB survive and have an altered though functional immune response. T cells of mice lacking 4-1BB proliferate more rapidly than normal T cells, but have reduced cytokine secretion. The costimulatory signal provided by 4-1BB may act in combination with CD28 activation to prolong the T cell response, and may also act independently of CD28. Stimulation of T cells with the 4-1BB ligand may provide a therapeutic immune response in the treatment of cancer or viral infection. 4-1BB in T cells activates several signaling pathways. Like other members of the TNF receptor family, the 4-1BB receptor does not have an intrinsic kinase activity. TRAF2 is a signaling adapter that mediates signaling by other members of the TNF receptor family and that also binds to the cytoplasmic domain of ligand activated 4-1BB to activate intracellular kinase cascades. TRAF1 also binds to the cytoplasmic domain of 4-1BB although with lower affinity than TRAF2. One downstream effector activated by 4-1BB through TRAF2 is the transcription factor NF-kB. 4-1BB also activates map kinase pathways, including p38 and JNK activation. ASK1 dependent pathways can activate both p38 and JNK, and dominant negative ASK1 blocks their activation. Other kinase pathways may also be involved in 4-1BB activation of p38 and JNK, such as activation of germinal center kinase (GCK) or related kinases involved in activation of JNK and p38 by TNF. Map kinase activation along with NF-kB activation results in transcriptional activation of cytokine genes involved in T cell activation and signaling. The co-stimulatory signaling provided by 4-1BB shares some features with CD28 signaling, providing an explanation for the ability of 4-1BB to replace the CD28 costimulatory signal in some settings.More...
The process of hematopoesis is regulated by various cytokine......
The process of hematopoesis is regulated by various cytokines. The combination of cytokines stimulates the proliferation and/or differentiation of the various hematopoietic cell types. Bone marrow stromal cells are the major source of hematopoietic cytokines in the non-infecteous state. In the presence of infection, cytokines produced by activated macrophages and TH cells induce hematopoietic activity. The induction by cytokines results in rapid expansion of the population of white blood cells to fight infection. The specific cytokines that affect a step of cell differentiation are placed adjacent to the arrow representing that step. Lines with ? indicate likely, but still hypothetical pathways.More...
Interleukin 2 (IL-2) is a potent cytokine that can lead to c......
Interleukin 2 (IL-2) is a potent cytokine that can lead to cellular activation and proliferation. IL-2 Receptors are found on activated B-Cells, LPS treated Monocytes, and many T cells. The receptor is formed from three chains alpha (CD25), beta (CD122), and gamma (CD132). Primary signaling is through the JAK/Stat pathway and MAPKs.More...
IL2 related Reactome pathways (count: 0)
IL2 related interactors from protein-protein interaction data in HPRD (count: 9)
Basic Information
Positive relationships between IL2 and other components at different levels (count: 0)
