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The immune system is a network of biological systems that protects an organism from diseases. It detects and responds to a wide variety of pathogens, from viruses to parasitic worms, as well as cancer cells and objects such as wood splinters, distinguishing them from the organism's own healthy tissue. Many species have two major subsystems of the immune system. The innate immune system provides a preconfigured response to broad groups of situations and stimuli. The adaptive immune system provides a tailored response to each stimulus by learning to recognize molecules it has previously encountered. Both use molecules and cells to perform their functions.
Exocytosis is a form of active transport and bulk transport in which a cell transports molecules out of the cell. As an active transport mechanism, exocytosis requires the use of energy to transport material. Exocytosis and its counterpart, endocytosis, are used by all cells because most chemical substances important to them are large polar molecules that cannot pass through the hydrophobic portion of the cell membrane by passive means. Exocytosis is the process by which a large amount of molecules are released; thus it is a form of bulk transport. Exocytosis occurs via secretory portals at the cell plasma membrane called porosomes. Porosomes are permanent cup-shaped lipoprotein structure at the cell plasma membrane, where secretory vesicles transiently dock and fuse to release intra-vesicular contents from the cell.
In a neuron, synaptic vesicles store various neurotransmitters that are released at the synapse. The release is regulated by a voltage-dependent calcium channel. Vesicles are essential for propagating nerve impulses between neurons and are constantly recreated by the cell. The area in the axon that holds groups of vesicles is an axon terminal or "terminal bouton". Up to 130 vesicles can be released per bouton over a ten-minute period of stimulation at 0.2 Hz. In the visual cortex of the human brain, synaptic vesicles have an average diameter of 39.5 nanometers (nm) with a standard deviation of 5.1 nm.
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 cells, such as neutrophil elastase and cathepsin G.
Ira Mellman is an American cell biologist who discovered endosomes. He serves as Vice President of Research Oncology at Genentech in South San Francisco, California.
Cross-presentation is the ability of certain professional antigen-presenting cells (mostly dendritic cells) to take up, process and present extracellular antigens with MHC class I molecules to CD8 T cells (cytotoxic T cells). Cross-priming, the result of this process, describes the stimulation of naive cytotoxic CD8+ T cells into activated cytotoxic CD8+ T cells. This process is necessary for immunity against most tumors and against viruses that infect dendritic cells and sabotage their presentation of virus antigens. Cross presentation is also required for the induction of cytotoxic immunity by vaccination with protein antigens, for example, tumour vaccination.
Filopodia are slender cytoplasmic projections that extend beyond the leading edge of lamellipodia in migrating cells. Within the lamellipodium, actin ribs are known as microspikes, and when they extend beyond the lamellipodia, they're known as filopodia. They contain microfilaments cross-linked into bundles by actin-bundling proteins, such as fascin and fimbrin. Filopodia form focal adhesions with the substratum, linking them to the cell surface. Many types of migrating cells display filopodia, which are thought to be involved in both sensation of chemotropic cues, and resulting changes in directed locomotion.
CD28 is one of the proteins expressed on T cells that provide co-stimulatory signals required for T cell activation and survival. T cell stimulation through CD28 in addition to the T-cell receptor (TCR) can provide a potent signal for the production of various interleukins.
In immunology, an immunological synapse is the interface between an antigen-presenting cell or target cell and a lymphocyte such as a T/B cell or Natural Killer cell. The interface was originally named after the neuronal synapse, with which it shares the main structural pattern. An immunological synapse consists of molecules involved in T cell activation, which compose typical patterns—activation clusters. Immunological synapses are the subject of much ongoing research.
Antigen presentation is a vital immune process that is essential for T cell immune response triggering. Because T cells recognize only fragmented antigens displayed on cell surfaces, antigen processing must occur before the antigen fragment can be recognized by a T-cell receptor. Specifically, the fragment, bound to the major histocompatibility complex (MHC), is transported to the surface of the cell, a process known as presentation. If there has been an infection with viruses or bacteria, the cell will present an endogenous or exogenous peptide fragment derived from the antigen by MHC molecules. There are two types of MHC molecules which differ in the behaviour of the antigens: MHC class I molecules (MHC-I) bind peptides from the cell cytosol, while peptides generated in the endocytic vesicles after internalisation are bound to MHC class II (MHC-II). Cellular membranes separate these two cellular environments - intracellular and extracellular. Each T cell can only recognize tens to hundreds of copies of a unique sequence of a single peptide among thousands of other peptides presented on the same cell, because an MHC molecule in one cell can bind to quite a large range of peptides. Predicting which antigens will be presented to the immune system by a certain MHC/HLA type is difficult, but the technology involved is improving.
Dynactin is a 23 subunit protein complex that acts as a co-factor for the microtubule motor cytoplasmic dynein-1. It is built around a short filament of actin related protein-1 (Arp1).
Vesicle-associated membrane protein 3 is a protein that in humans is encoded by the VAMP3 gene.
CD226, PTA1 or DNAM-1 is a ~65 kDa immunoglobulin-like transmembrane glycoprotein expressed on the surface of natural killer cells, NK T cell, B cells, dendritic cells, hematopoietic precursor cells, platelets, monocytes and T cells.
-Cytosis is a suffix that either refers to certain aspects of cells ie cellular process or phenomenon or sometimes refers to predominance of certain type of cells. It essentially means "of the cell". Sometimes it may be shortened to -osis and may be related to some of the processes ending with -esis or similar suffixes.
The ribbon synapse is a type of neuronal synapse characterized by the presence of an electron-dense structure, the synaptic ribbon, that holds vesicles close to the active zone. It is characterized by a tight vesicle-calcium channel coupling that promotes rapid neurotransmitter release and sustained signal transmission. Ribbon synapses undergo a cycle of exocytosis and endocytosis in response to graded changes of membrane potential. It has been proposed that most ribbon synapses undergo a special type of exocytosis based on coordinated multivesicular release. This interpretation has recently been questioned at the inner hair cell ribbon synapse, where it has been instead proposed that exocytosis is described by uniquantal release shaped by a flickering vesicle fusion pore.
Immunoevasins are proteins expressed by some viruses that enable the virus to evade immune recognition by interfering with MHC I complexes in the infected cell, therefore blocking the recognition of viral protein fragments by CD8+ cytotoxic T lymphocytes. Less frequently, MHC II antigen presentation and induced-self molecules may also be targeted. Some viral immunoevasins block peptide entry into the endoplasmic reticulum (ER) by targeting the TAP transporters. Immunoevasins are particularly abundant in viruses that are capable of establishing long-term infections of the host, such as herpesviruses.
Kiss-and-run fusion is a type of synaptic vesicle release where the vesicle opens and closes transiently. In this form of exocytosis, the vesicle docks and transiently fuses at the presynaptic membrane and releases its neurotransmitters across the synapse, after which the vesicle can then be reused.
Sfi1 homolog, spindle assembly associated (yeast) is a protein that in humans is encoded by the SFI1 gene. It localizes to the centriole, and its S. pombe ortholog has been shown to be involved in spindle pole body duplication. SFI1 forms a complex with centrin 2.
Daniel Michael Davis is Head of Life Sciences and Professor of Immunology at Imperial College London. Davis was previously Professor of Immunology at the University of Manchester. He is the author of The Secret Body, The Beautiful Cure and The Compatibility Gene. His research, using microscopy to study immune cell biology has helped understand how immune cells interact with each other. He co-discovered the immunological synapse and membrane nanotubes.
Charles Bangham holds the Chair in Immunology at Imperial College London.
References
- 1 2 3 "Professor Gillian Griffiths FMedSci FRS". The Royal Society. Archived from the original on 20 June 2019. Retrieved 11 October 2013.
- ↑ Stinchcombe, J. C.; Salio, M; Cerundolo, V; Pende, D; Arico, M; Griffiths, G. M. (2011). "Centriole polarisation to the immunological synapse directs secretion from cytolytic cells of both the innate and adaptive immune systems". BMC Biology. 9: 45. doi: 10.1186/1741-7007-9-45 . PMC 3149597 . PMID 21711522.
- ↑ Tsun, A; Qureshi, I; Stinchcombe, J. C.; Jenkins, M. R.; de la Roche, M; Kleczkowska, J; Zamoyska, R; Griffiths, G. M. (2011). "Centrosome docking at the immunological synapse is controlled by Lck signaling". The Journal of Cell Biology. 192 (4): 663–74. doi:10.1083/jcb.201008140. PMC 3044125 . PMID 21339332.
- ↑ Griffiths, G. M.; Tsun, A.; Stinchcombe, J. C. (2010). "The immunological synapse: A focal point for endocytosis and exocytosis". The Journal of Cell Biology. 189 (3): 399–406. doi:10.1083/jcb.201002027. PMC 2867296 . PMID 20439993.
- ↑ Cetica, V; Santoro, A; Gilmour, K. C.; Sieni, E; Beutel, K; Pende, D; Marcenaro, S; Koch, F; Grieve, S; Wheeler, R; Zhao, F; Zur Stadt, U; Griffiths, G. M.; Aricò, M (2010). "STXBP2 mutations in children with familial haemophagocytic lymphohistiocytosis type 5". Journal of Medical Genetics. 47 (9): 595–600. doi:10.1136/jmg.2009.075341. PMC 4115259 . PMID 20798128.
- ↑ Gillian Griffiths's publications indexed by the Scopus bibliographic database. (subscription required)
- ↑ Sedwick, C. (2013). "Gillian Griffiths: How T cells get on target". The Journal of Cell Biology. 200 (1): 4–5. doi:10.1083/jcb.2001pi. PMC 3542799 . PMID 23295346.
- ↑ "Buchanan Medallist 2019". Royal Society. Retrieved 5 October 2019.
