CD40L
CD154, also called CD40 ligand or CD40L, is a protein that is primarily expressed on activated T cells and is a member of the TNF superfamily of molecules. It binds to CD40 (protein), CD40 on antigen-presenting cells (APC), which leads to many effects depending on the target cell type. In total CD40L has three binding partners: CD40, Alpha-5 beta-1, α5β1 integrin and integrin αIIbβ3. CD154 acts as a costimulatory molecule and is particularly important on a subset of T cells called Follicular B helper T cells, T follicular helper cells (TFH cells). On TFH cells, CD154 promotes B cell maturation and function by engaging CD40 on the B cell surface and therefore facilitating cell-cell communication. A defect in this gene results in an inability to undergo immunoglobulin class switching and is associated with hyper IgM syndrome. Absence of CD154 also stops the formation of germinal centers and therefore prohibits antibody affinity maturation, an important process in the adaptive im ... [...More Info...]       [...Related Items...]     OR:     [Wikipedia]   [Google]   [Baidu]   |
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CD40
Cluster of differentiation 40, CD40 is a type I transmembrane protein found on antigen-presenting cells and is required for their activation. The binding of CD154 (CD40L) on T helper cell, TH cells to CD40 activates antigen presenting cells and induces a variety of downstream effects. Activated CD4+ T cells primarily exhibit its ligand CD40L/CD154 to antigen-presenting cells including dendritic cells (DCs), B cells, macrophages, classical and non-classical monocytes, on a variety of non-immune cells including platelets and endothelial cells, and on several types of tumor cells. Mutations affecting this gene are the cause of autosomal recessive Hyper IgM syndrome, hyper-IgM immunodeficiency. Discovery Between the late 1950s and the mid-1980s, several immunology laboratories started to use the new hybridoma technology to develop Monoclonal antibody, monoclonal antibodies (mAbs) and define receptors expressed at different stages of hematopoietic cell differentiation. The goal of ... [...More Info...]       [...Related Items...]     OR:     [Wikipedia]   [Google]   [Baidu]   |
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CD40 (protein)
Cluster of differentiation 40, CD40 is a type I transmembrane protein found on antigen-presenting cells and is required for their activation. The binding of CD154 ( CD40L) on TH cells to CD40 activates antigen presenting cells and induces a variety of downstream effects. Activated CD4+ T cells primarily exhibit its ligand CD40L/CD154 to antigen-presenting cells including dendritic cells (DCs), B cells, macrophages, classical and non-classical monocytes, on a variety of non-immune cells including platelets and endothelial cells, and on several types of tumor cells. Mutations affecting this gene are the cause of autosomal recessive hyper-IgM immunodeficiency. Discovery Between the late 1950s and the mid-1980s, several immunology laboratories started to use the new hybridoma technology to develop monoclonal antibodies (mAbs) and define receptors expressed at different stages of hematopoietic cell differentiation. The goal of these experiments was to identify differentiation ... [...More Info...]       [...Related Items...]     OR:     [Wikipedia]   [Google]   [Baidu]   |
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Hyper IgM Syndrome
Hyper IgM syndrome is a rare primary immune deficiency disorders characterized by low or absent levels of serum IgG, IgA, IgE and normal or increased levels of serum IgM. They are resulting from mutations in the pathway from B-cell activation to isotype class switching. Patients with HIGM are usually diagnosed within the first two years of life and experience severe immunosuppression. This syndrome is also known as immunoglobulin class switch recombination (Ig-CSR) deficiencies. The most common causes are mutations in the CD40 Ligand (''CD40LG'') gene located at Xq26.3-27 leading to X-linked HIGM (XHIGM) in males. Types Five types of hyper IgM syndrome have been characterized: * '' Hyper-IgM syndrome type 1'' (X-linked), characterized by mutations of the '' CD40LG'' gene. In this type, lack of CD40L on the surfaces of T cells results in defective signaling to B cells, which do not receive the needed signal to undergo isotype switching. Therefore, the only antibody secreted by ... [...More Info...]       [...Related Items...]     OR:     [Wikipedia]   [Google]   [Baidu]   |
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Seth Lederman
Seth Lederman (born July 30, 1957) is an American physician, scientist and specialty pharmaceuticals entrepreneur. He is a co-founder and the current President and Chairman of Tonix Pharmaceuticals, a specialty pharmaceutical product development and commercialization company. Biography Lederman earned his bachelor's degree in chemistry from Princeton University where he graduated ''cum laude'' in 1979. He completed his M.D. from Columbia University in 1983 and continued his training at the Columbia Presbyterian Medical Center until 1986. Lederman became an instructor at Columbia in 1985, assistant professor in 1988 and associate professor with tenure in 1996. From October 30, 2015, until November 1, 2016, he took a leave of absence, and left Columbia in April 2017. In addition to his research, he served as attending physician in the Edward Daniels Faulkner Arthritis Clinic at Columbia Presbyterian Hospital from 1988 to 1996 and served as associate attending physician at Columbia ... [...More Info...]       [...Related Items...]     OR:     [Wikipedia]   [Google]   [Baidu]   |
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Follicular B Helper T Cells
Follicular helper T cells (also known as T follicular helper cells and abbreviated as TFH), are antigen-experienced CD4+ T cells found in the periphery within B cell Lymph_node#Subdivisions, follicles of secondary lymphoid organs such as lymph nodes, spleen and Peyer's patches, and are identified by their constitutive expression of the B cell follicle homing receptor CXCR5. Upon cellular interaction and cross-signaling with their cognate Follicular B cell, follicular (Fo B) B cells, TFH cells trigger the formation and maintenance of germinal centers through the expression of CD40L, CD40 ligand (CD40L) and the secretion of Interleukin 21, IL-21 and Interleukin-4, IL-4. TFH cells also migrate from T cell zones into these seeded germinal centers, predominantly composed of rapidly dividing B cells somatic hypermutation, mutating their Ig genes. Within germinal centers, TFH cells play a critical role in mediating the selection and survival of B cells that go on to differentiate either i ... [...More Info...]       [...Related Items...]     OR:     [Wikipedia]   [Google]   [Baidu]   |
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Germinal Center
Germinal centers or germinal centres (GCs) are transiently formed structures within B cell zone (follicles) in secondary lymphoid organs – lymph nodes, ileal Peyer's patches, and the spleen – where mature B cells are activated, proliferate, differentiate, and mutate their antibody genes (through somatic hypermutation aimed at achieving higher affinity) during a normal immune response; most of the germinal center B cells (BGC) are removed by tingible body macrophages. There are several key differences between naive B cells and GC B cells, including level of proliferative activity, size, metabolic activity and energy production. The B cells develop dynamically after the activation of follicular B cells by T-dependent antigen. The initiation of germinal center formation involves the interaction between B and T cells in the interfollicular area of the lymph node, CD40-CD40L ligation, NF-kB signaling and expression of IRF4 and BCL6. GC B cells cycle through the two distinct ... [...More Info...]       [...Related Items...]     OR:     [Wikipedia]   [Google]   [Baidu]   |
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Macrophage
Macrophages (; abbreviated MPhi, φ, MΦ or MP) 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 self-protection method can be contrasted with that employed by Natural killer cell, Natural Killer cells. This process of engulfment and digestion is called phagocytosis; it acts to defend the host against infection and injury. Macrophages are found in essentially all tissues, where they patrol for potential pathogens by amoeboid movement. They take various forms (with various names) throughout the body (e.g., histiocytes, Kupffer cells, alveolar macrophages, microglia, and others), but all are part of the mononuclear phagocyte system. Besides phagocytosis, they play a critical role in nonspecific defense (innate immunity) and also help initiate specific defense mechanisms (adapti ... [...More Info...]       [...Related Items...]     OR:     [Wikipedia]   [Google]   [Baidu]   |
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B Cell
B cells, also known as B lymphocytes, are a type of the lymphocyte subtype. They function in the humoral immunity component of the adaptive immune system. B cells produce antibody molecules which may be either secreted or inserted into the plasma membrane where they serve as a part of B-cell receptors. When a naïve or memory B cell is activated by an antigen, it proliferates and differentiates into an antibody-secreting effector cell, known as a plasmablast or plasma cell. In addition, B cells Antigen presentation, present antigens (they are also classified as professional Antigen-presenting cell, antigen-presenting cells, APCs) and secrete cytokines. In mammals B cells Cellular differentiation, mature in the bone marrow, which is at the core of most bones. In birds, B cells mature in the bursa of Fabricius, a lymphoid organ where they were first discovered by Chang and Glick, which is why the ''B'' stands for ''bursa'' and not ''bone marrow'', as commonly believed. B cells, unl ... [...More Info...]       [...Related Items...]     OR:     [Wikipedia]   [Google]   [Baidu]   |
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Tumor Necrosis Factors
The tumor necrosis factor (TNF) superfamily is a protein superfamily of transmembrane protein#Classification by topology, type II transmembrane proteins containing TNF homology domain and forming Protein trimer, trimers. Members of this superfamily can be released from the cell membrane by extracellular proteolytic cleavage and function as a cytokine. These proteins are expressed predominantly by immune cells and they regulate diverse cell functions, including immune response and inflammation, but also proliferation, differentiation, apoptosis and embryogenesis. The superfamily contains 19 members that bind to 29 members of TNF receptor superfamily. An occurrence of Sequence homology#Orthology, orthologs in invertebrates hints at ancient origin of this superfamily in evolution. The PROSITE pattern of this superfamily is located in a beta sheet in the central section of the protein that is conserved across all members. Members There are 19 family members, numerically classifie ... [...More Info...]       [...Related Items...]     OR:     [Wikipedia]   [Google]   [Baidu]   |
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Helper T Cell
The T helper cells (Th cells), also known as CD4+ cells or CD4-positive cells, are a type of T cell that play an important role in the adaptive immune system. They aid the activity of other immune cells by releasing cytokines. They are considered essential in B cell antibody class switching, breaking cross-tolerance in dendritic cells, in the activation and growth of cytotoxic T cells, and in maximizing bactericidal activity of phagocytes such as macrophages and neutrophils. CD4+ cells are mature Th cells that express the surface protein CD4. Genetic variation in regulatory elements expressed by CD4+ cells determines susceptibility to a broad class of autoimmune diseases. Structure and function Th cells contain and release cytokines to aid other immune cells. Cytokines are small protein mediators that alter the behavior of target cells that express receptors for those cytokines. These cells help polarize the immune response depending on the nature of the immunological ins ... [...More Info...]       [...Related Items...]     OR:     [Wikipedia]   [Google]   [Baidu]   |
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Memory B Cell
In immunology, a memory B cell (MBC) is a type of B lymphocyte that forms part of the adaptive immune system. These cells develop within germinal centers of the secondary lymphoid organs. Memory B cells circulate in the blood stream in a quiescent state, sometimes for decades. Their function is to memorize the characteristics of the antigen that activated their parent B cell during initial infection such that if the memory B cell later encounters the same antigen, it triggers an accelerated and robust secondary immune response. Memory B cells have B cell receptors (BCRs) on their cell membrane, identical to the one on their parent cell, that allow them to recognize antigen and mount a specific antibody response. Development and activation T cell dependent mechanisms In a T-cell dependent development pathway, naïve follicular B cells are activated by antigen-presenting follicular B helper T cells (TFH) during the initial infection, or primary immune response. Naïve ... [...More Info...]       [...Related Items...]     OR:     [Wikipedia]   [Google]   [Baidu]   |
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Antigen-presenting Cells
An antigen-presenting cell (APC) or accessory cell is a cell that displays an antigen bound by major histocompatibility complex (MHC) proteins on its surface; this process is known as antigen presentation. T cells may recognize these complexes using their T cell receptors (TCRs). APCs process antigens and present them to T cells. Almost all cell types can present antigens in some way. They are found in a variety of tissue types. Dedicated antigen-presenting cells, including macrophages, B cells and dendritic cells, present foreign antigens to helper T cells, while virus-infected cells (or cancer cells) can present antigens originating inside the cell to cytotoxic T cells. In addition to the MHC family of proteins, antigen presentation relies on other specialized signaling molecules on the surfaces of both APCs and T cells. Antigen-presenting cells are vital for effective adaptive immune response, as the functioning of both cytotoxic and helper T cells is dependent on APCs. Ant ... [...More Info...]       [...Related Items...]     OR:     [Wikipedia]   [Google]   [Baidu]   |