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Perforin
Perforin-1 Perforin (PRF), encoded by the PRF1 gene, is a pore-forming toxic protein housed in the secretory granules of cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells. Together, these cells are known as cytotoxic lymphocytes (CLs). Discovery Perforin was initially discovered in 1983 and subsequently cloned from an expression library in 1988 using anti-complement C9 antibody cross-reactivity. A sequence comparison showed a notable resemblance between the two proteins in a specific central region, termed the 'membrane attack complex/perforin' (MACPF) domain. Structure and Function Purifying perforin is challenging due to its tendency to lose activity and stability in solution, and only recently has a recombinant form been successfully produced. Perforin is a pore forming cytolytic protein found in the granules of cytotoxic T lymphocytes (CTLs) and natural killer cells (NK cells). Upon degranulation, perforin molecules translocate to the target cell with the he ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
MACPF
The Membrane Attack Complex/Perforin (MACPF) superfamily, sometimes referred to as the MACPF/CDC superfamily, is named after a domain that is common to the membrane attack complex (MAC) proteins of the complement system (C6, C7, C8α, C8β and C9) and perforin (PF). Members of this protein family are pore-forming toxins (PFTs). In eukaryotes, MACPF proteins play a role in immunity and development. Archetypal members of the family are complement C9 and perforin, both of which function in human immunity. C9 functions by punching holes in the membranes of Gram-negative bacteria. Perforin is released by cytotoxic T cells and lyses virally infected and transformed cells. In addition, perforin permits delivery of cytotoxic proteases called granzymes that cause cell death. Deficiency of either protein can result in human disease. Structural studies reveal that MACPF domains are related to cholesterol-dependent cytolysins (CDCs), a family of pore forming toxins previously ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Granzyme
Granzymes are serine proteases released by cytoplasmic granules within cytotoxic T cells and natural killer (NK) cells. They induce programmed cell death (apoptosis) in the target cell, thus eliminating cells that have become cancerous or are infected with viruses or bacteria. Granzymes also kill bacteria and inhibit viral replication. In NK cells and T cells, granzymes are packaged in cytotoxic granules along with perforin. Granzymes can also be detected in the rough endoplasmic reticulum, golgi complex, and the trans-golgi reticulum. The contents of the cytotoxic granules function to permit entry of the granzymes into the target cell cytosol. The granules are released into an immune synapse formed with a target cell, where perforin mediates the delivery of the granzymes into endosomes in the target cell, and finally into the target cell cytosol. Granzymes are part of the serine esterase family. They are closely related to other immune serine proteases expressed by innate immune ce ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
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 glycoprotei ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Granzyme B
Granzyme B (GrB) is one of the serine protease granzymes most commonly found in the granules of natural killer cells (NK cells) and cytotoxic T cells. It is secreted by these cells along with the pore forming protein perforin to mediate apoptosis in target cells. Granzyme B has also been found to be produced by a wide range of non-cytotoxic cells ranging from basophils and mast cells to smooth muscle cells. The secondary functions of granzyme B are also numerous. Granzyme B has shown to be involved in inducing inflammation by stimulating cytokine release and is also involved in extracellular matrix remodelling. Elevated levels of granzyme B are also implicated in a number of autoimmune diseases, several skin diseases, and type 1 diabetes. Structure In humans, granzyme B is encoded by ''GZMB'' on chromosome 14q.11.2, which is 3.2kb long and consists of 5 exons. It is one of the most abundant granzymes of which there are 5 in humans and 10 in mice. Granzyme B is thought to hav ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Natural Killer Cell
Natural killer cells, also known as NK cells, are a type of cytotoxic lymphocyte critical to the innate immune system. They are a kind of large granular lymphocytes (LGL), and belong to the rapidly expanding family of known innate lymphoid cells (ILC) and represent 5–20% of all circulating lymphocytes in humans. The role of NK cells is analogous to that of cytotoxic T cells in the vertebrate adaptive immune response. NK cells provide rapid responses to virus-infected cells, stressed cells, tumor cells, and other intracellular pathogens based on signals from several activating and inhibitory receptors. Most immune cells detect the antigen presented on MHC class I, major histocompatibility complex I (MHC-I) on infected cell surfaces, but NK cells can recognize and kill stressed cells in the absence of antibodies and MHC, allowing for a much faster immune reaction. They were named "natural killers" because of the notion that they do not require activation to kill cells that are m ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Hemophagocytic Lymphohistiocytosis
In hematology, hemophagocytic lymphohistiocytosis (HLH), also known as haemophagocytic lymphohistiocytosis ( British spelling), and hemophagocytic or haemophagocytic syndrome, is an uncommon hematologic disorder seen more often in children than in adults. It is a life-threatening disease of severe hyperinflammation caused by uncontrolled proliferation of benign lymphocytes and macrophages that secrete high amounts of inflammatory cytokines. It is classified as one of the cytokine storm syndromes. There are inherited (primary HLH) and acquired (secondary HLH) forms. The inherited form is due to genetic mutations and usually presents in infants and children, with a median age of onset of 3-6 months. Familial HLH is an autosomal recessive disease, hence each sibling of a child with familial HLH has a twenty-five–percent chance of developing the disease, a fifty-percent chance of carrying the defective gene (which is very rarely associated with any risk of disease), and a twenty ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Programmed Cell Death
Programmed cell death (PCD) sometimes referred to as cell, or cellular suicide is the death of a cell (biology), cell as a result of events inside of a cell, such as apoptosis or autophagy. PCD is carried out in a biological process, which usually confers advantage during an organism's biological life cycle, lifecycle. For example, the Limb development, differentiation of fingers and toes in a developing human embryo occurs because cells between the fingers apoptose; the result is that the digits are separate. PCD serves fundamental functions during both plant and animal tissue development. Apoptosis and autophagy are both forms of programmed cell death. Necrosis is the death of a cell caused by external factors such as trauma or infection and occurs in several different forms. Necrosis was long seen as a non-physiological process that occurs as a result of infection or injury, but in the 2000s, a form of programmed necrosis, called necroptosis, was recognized as an alternative f ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Complement Component 9
Complement component 9 (C9) is a MACPF protein involved in the complement system, which is part of the innate immune system. Once activated, about 12-18 molecules of C9 polymerize to form pores in target cell membranes, causing lysis and cell death. C9 is one member of the complement membrane attack complex (MAC), which also includes complement components C5b, C6, C7 and C8. The formation of the MAC occurs through three distinct pathways: the classical, alternative, and lectin pathways. Pore formation by C9 is an important way that bacterial cells are killed during an infection, and the target cell is often covered in multiple MACs. The clinical impact of a deficiency in C9 is an infection with the gram-negative bacterium ''Neisseria meningitidis.'' Structure C9 genes include 11 exons and 10 introns An intron is any Nucleic acid sequence, nucleotide sequence within a gene that is not expressed or operative in the final RNA product. The word ''intron'' is derived from th ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Cytolysin
Cytolysin refers to the substance secreted by microorganisms, plants or animals that is specifically toxic to individual cells, in many cases causing their dissolution through lysis. Cytolysins that have a specific action for certain cells are named accordingly. For instance, the cytolysins responsible for the destruction of red blood cells, thereby liberating hemoglobins, are named '' hemolysins'', and so on. Cytolysins may be involved in immunity as well as in venoms. Hemolysin is also used by certain bacteria, such as '' Listeria monocytogenes'', to disrupt the phagosome membrane of macrophages and escape into the cytoplasm of the cell. History and background The term "Cytolysin" or "Cytolytic toxin" was first introduced by Alan Bernheimer to describe membrane damaging toxins ( MDTs) that have cytolytic effects to cells. The first kind of cytolytic toxin discovered have hemolytic effects on erythrocytes of certain sensitive species, such as Human. For this reason " Hemol ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Calreticulin
Calreticulin also known as calregulin, CRP55, CaBP3, calsequestrin-like protein, and endoplasmic reticulum resident protein 60 (ERp60) is a protein that in humans is encoded by the ''CALR'' gene. Calreticulin is a multifunctional soluble protein that binds Ca2+ ions (a second messenger in signal transduction), rendering them inactive. The Ca2+ is bound with low affinity, but high capacity, and can be released on a signal (see inositol trisphosphate). Calreticulin is located in storage compartments associated with the endoplasmic reticulum and is considered an ER resident protein. The term "Mobilferrin" is considered to be the same as calreticulin by some sources. Function Calreticulin binds to misfolded proteins and prevents them from being exported from the endoplasmic reticulum to the Golgi apparatus. A similar quality-control molecular chaperone, calnexin, performs the same service for soluble proteins as does calreticulin, however it is a membrane-bound protein. ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Joseph Trapani (immunologist)
Joseph Albert Trapani is an Australian immunologist. Trapani studied at the University of Melbourne and did his PhD in the immunogenetics of B27-related arthropathy. He later discovered that the protein perforin forms pores in the target cell and provides access for granzymes to enter and trigger cell death by apoptosis. Since 1995, Trapania has worked on developing CAR T therapy for treating cancer. Trapani became an Officer of the Order of Australia The Order of Australia is an Australian honours and awards system, Australian honour that recognises Australian citizens and other persons for outstanding achievement and service. It was established on 14 February 1975 by Elizabeth II, Monarch ... in the 2024 Australia Day Honours for "distinguished service to medical research, particularly immunology and the development of immune-based cancer therapies, and to the community." References {{DEFAULTSORT:Trapani, Joseph Living people Australian immunologists Officers of ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
