Follicular B Helper T Cells
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Follicular B Helper T Cells
Follicular helper T cells (also known as follicular B helper T cells and abbreviated as TFH), are antigen-experienced CD4+ T cells found in the periphery within B cell 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 (Fo B) B cells, TFH cells trigger the formation and maintenance of germinal centers through the expression of CD40 ligand (CD40L) and the secretion of IL-21 and IL-4. TFH cells also migrate from T cell zones into these seeded germinal centers, predominantly composed of rapidly dividing B cells 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 into long-lived plasma cells capable of producing high affinity antibodies against foreign antigen ...
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Antigen
In immunology, an antigen (Ag) is a molecule or molecular structure or any foreign particulate matter or a pollen grain that can bind to a specific antibody or T-cell receptor. The presence of antigens in the body may trigger an immune response. The term ''antigen'' originally referred to a substance that is an antibody generator. Antigens can be proteins, peptides (amino acid chains), polysaccharides (chains of monosaccharides/simple sugars), lipids, or nucleic acids. Antigens are recognized by antigen receptors, including antibodies and T-cell receptors. Diverse antigen receptors are made by cells of the immune system so that each cell has a specificity for a single antigen. Upon exposure to an antigen, only the lymphocytes that recognize that antigen are activated and expanded, a process known as clonal selection. In most cases, an antibody can only react to and bind one specific antigen; in some instances, however, antibodies may cross-react and bind more than one antigen. ...
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Autoimmunity
In immunology, autoimmunity is the system of immune responses of an organism against its own healthy cells, tissues and other normal body constituents. Any disease resulting from this type of immune response is termed an "autoimmune disease". Prominent examples include celiac disease, post-infectious IBS, diabetes mellitus type 1, Henoch–Schönlein purpura (HSP) sarcoidosis, systemic lupus erythematosus (SLE), Sjögren syndrome, eosinophilic granulomatosis with polyangiitis, Hashimoto's thyroiditis, Graves' disease, idiopathic thrombocytopenic purpura, Addison's disease, rheumatoid arthritis (RA), ankylosing spondylitis, polymyositis (PM), dermatomyositis (DM), Alopecia Areata and multiple sclerosis (MS). Autoimmune diseases are very often treated with steroids. Autoimmunity means presence of antibodies or T cells that react with self-protein and is present in all individuals, even in normal health state. It causes autoimmune diseases if self-reactivity can lead to tiss ...
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Vaccine
A vaccine is a biological Dosage form, preparation that provides active acquired immunity to a particular infectious disease, infectious or cancer, malignant disease. The safety and effectiveness of vaccines has been widely studied and verified. A vaccine typically contains an agent that resembles a disease-causing microorganism and is often made from weakened or Antigen, killed forms of the microbe, its toxins, or one of its surface proteins. The agent stimulates the body's immune system to recognize the agent as a threat, destroy it, and to further recognize and destroy any of the microorganisms associated with that agent that it may encounter in the future. Vaccines can be prophylaxis, prophylactic (to prevent or ameliorate the effects of a future infection by a natural or "wild" pathogen), or therapeutic vaccines, therapeutic (to fight a disease that has already occurred, such as cancer vaccine, cancer).
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Immunization
Immunization, or immunisation, is the process by which an individual's immune system becomes fortified against an infectious agent (known as the immunogen). When this system is exposed to molecules that are foreign to the body, called ''non-self'', it will orchestrate an immune response, and it will also develop the ability to quickly respond to a subsequent encounter because of immunological memory. This is a function of the adaptive immune system. Therefore, by exposing a human, or an animal, to an immunogen in a controlled way, its body can learn to protect itself: this is called active immunization. The most important elements of the immune system that are improved by immunization are the T cells, B cells, and the antibodies B cells produce. Memory B cells and memory T cells are responsible for a swift response to a second encounter with a foreign molecule. Passive immunization is direct introduction of these elements into the body, instead of production of these elements b ...
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Affinity Maturation
In immunology, affinity maturation is the process by which TFH cell-activated B cells produce antibodies with increased affinity for antigen during the course of an immune response. With repeated exposures to the same antigen, a host will produce antibodies of successively greater affinities. A secondary response can elicit antibodies with several fold greater affinity than in a primary response. Affinity maturation primarily occurs on membrane immunoglobulin of germinal center B cells and as a direct result of somatic hypermutation (SHM) and selection by TFH cells. __TOC__ ''In vivo'' The process is thought to involve two interrelated processes, occurring in the germinal centers of the secondary lymphoid organs: # Somatic hypermutation: Mutations in the variable, antigen-binding coding sequences (known as complementarity-determining regions (CDR)) of the immunoglobulin genes. The mutation rate is up to 1,000,000 times higher than in cell lines outside the lymphoid system. ...
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Foxp3
FOXP3 (forkhead box P3), also known as scurfin, is a protein involved in immune system responses. A member of the FOX protein family, FOXP3 appears to function as a master regulator of the regulatory pathway in the development and function of regulatory T cells. Regulatory T cells generally turn the immune response down. In cancer, an excess of regulatory T cell activity can prevent the immune system from destroying cancer cells. In autoimmune disease, a deficiency of regulatory T cell activity can allow other autoimmune cells to attack the body's own tissues. While the precise control mechanism has not yet been established, FOX proteins belong to the forkhead/winged-helix family of transcriptional regulators and are presumed to exert control via similar DNA binding interactions during transcription. In regulatory T cell model systems, the FOXP3 transcription factor occupies the promoters for genes involved in regulatory T-cell function, and may inhibit transcription of key gene ...
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Activation-induced (cytidine) Deaminase
Activation-induced cytidine deaminase, also known as AICDA, AID and single-stranded DNA cytosine deaminase, is a 24 kDa enzyme which in humans is encoded by the ''AICDA'' gene. It creates mutations in DNA by deamination of cytosine base, which turns it into uracil (which is recognized as a thymine). In other words, it changes a C:G base pair into a U:G mismatch. The cell's DNA replication machinery recognizes the U as a T, and hence C:G is converted to a T:A base pair. During germinal center development of B lymphocytes, AID also generates other types of mutations, such as C:G to A:T. The mechanism by which these other mutations are created is not well understood. It is a member of the APOBEC family. In B cells in the lymph nodes, AID causes mutations that produce antibody diversity, but that same mutation process leads to B cell lymphoma. Function This gene encodes a DNA-editing deaminase that is a member of the cytidine deaminase family. The protein is involved in somati ...
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Paracrine Signalling
Paracrine signaling is a form of cell signaling, a type of cellular communication in which a cell produces a signal to induce changes in nearby cells, altering the behaviour of those cells. Signaling molecules known as paracrine factors diffuse over a relatively short distance (local action), as opposed to cell signaling by endocrine factors, hormones which travel considerably longer distances via the circulatory system; juxtacrine interactions; and autocrine signaling. Cells that produce paracrine factors secrete them into the immediate extracellular environment. Factors then travel to nearby cells in which the gradient of factor received determines the outcome. However, the exact distance that paracrine factors can travel is not certain. Although paracrine signaling elicits a diverse array of responses in the induced cells, most paracrine factors utilize a relatively streamlined set of receptors and pathways. In fact, different organs in the body - even between different speci ...
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Cytotoxic T Cell
A cytotoxic T cell (also known as TC, cytotoxic T lymphocyte, CTL, T-killer cell, cytolytic T cell, CD8+ T-cell or killer T cell) is a T lymphocyte (a type of white blood cell) that kills cancer cells, cells that are infected by intracellular pathogens (such as viruses or bacteria), or cells that are damaged in other ways. Most cytotoxic T cells express T-cell receptors (TCRs) that can recognize a specific antigen. An antigen is a molecule capable of stimulating an immune response and is often produced by cancer cells, viruses, bacteria or intracellular signals. Antigens inside a cell are bound to class I MHC molecules, and brought to the surface of the cell by the class I MHC molecule, where they can be recognized by the T cell. If the TCR is specific for that antigen, it binds to the complex of the class I MHC molecule and the antigen, and the T cell destroys the cell. In order for the TCR to bind to the class I MHC molecule, the former must be accompanied by a glycoprotein ...
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BCL6
Bcl-6 (B-cell lymphoma 6) is a protein that in humans is encoded by the ''BCL6'' gene. BCL6 is a master transcription factor for regulation of T follicular helper cells (TFH cells) proliferation. BCL6 has three evolutionary conserved structural domains. The interaction of these domains with corepressors allows for germinal center development and leads to B cell proliferation. The ''deletion'' of BCL6 is known to lead to failure to germinal center formation in the follicles of the lymph nodes, preventing B cells from undergoing somatic hypermutation. ''Mutations'' in BCL6 can lead to B cell lymphomas because it promotes unchecked B cell growth. Clinically, BCL6 can be used to diagnose B cell lymphomas and is shown to be upregulated in a number of cancers. Other BCL genes, including BCL2, BCL3, BCL5, BCL7A, BCL9, and BCL10, also have clinical significance in lymphoma. Normal Physiological Function Structure The protein encoded by the BCL6 gene is a zinc finger transcription f ...
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CD278
Inducible T-cell costimulator is an immune checkpoint protein that in humans is encoded by the ''ICOS'' gene. CD278 or ICOS (Inducible T-cell COStimulator) is a CD28-superfamily costimulatory molecule that is expressed on activated T cells. It is thought to be important for Th2 cells in particular. Function The protein encoded by this gene belongs to the CD28 and CTLA-4 cell-surface receptor family. It forms homodimers and plays an important role in cell-cell signaling, immune responses and regulation of cell proliferation. Knockout phenotype Compared to wild-type naïve T cells, ICOS-/- T cells activated with plate-bound anti- CD3 have reduced proliferation and IL-2 secretion. The defect in proliferation can be rescued by addition of IL-2 to the culture, suggesting the proliferative defect is due either to ICOS-mediated IL-2 secretion or the activation of similar signaling pathways between ICOS and IL-2. In terms of Th1 and Th2 cytokine secretion, ICOS-/- CD4+ T cell a ...
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Regulatory T Cell
The regulatory T cells (Tregs or Treg cells), formerly known as suppressor T cells, are a subpopulation of T cells that modulate the immune system, maintain tolerance to self-antigens, and prevent autoimmune disease. Treg cells are immunosuppressive and generally suppress or downregulate induction and proliferation of effector T cells. Treg cells express the biomarkers CD4, FOXP3, and CD25 and are thought to be derived from the same lineage as naïve CD4+ cells. Because effector T cells also express CD4 and CD25, Treg cells are very difficult to effectively discern from effector CD4+, making them difficult to study. Research has found that the cytokine transforming growth factor beta (TGF-β) is essential for Treg cells to differentiate from naïve CD4+ cells and is important in maintaining Treg cell homeostasis. Mouse models have suggested that modulation of Treg cells can treat autoimmune disease and cancer and can facilitate orga ...
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