The immune system is a network of biological processes 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.
Ubiquitin is a small regulatory protein found in most tissues of eukaryotic organisms, i.e., it is found ubiquitously. It was discovered in 1975 by Gideon Goldstein and further characterized throughout the late 1970s and 1980s. Four genes in the human genome code for ubiquitin: UBB, UBC, UBA52 and RPS27A.
Hemocyanins (also spelled haemocyanins and abbreviated Hc) are proteins that transport oxygen throughout the bodies of some invertebrate animals. These metalloproteins contain two copper atoms that reversibly bind a single oxygen molecule (O2). They are second only to hemoglobin in frequency of use as an oxygen transport molecule. Unlike the hemoglobin in red blood cells found in vertebrates, hemocyanins are not confined in blood cells but are instead suspended directly in the hemolymph. Oxygenation causes a color change between the colorless Cu(I) deoxygenated form and the blue Cu(II) oxygenated form.
Caspases are a family of protease enzymes playing essential roles in programmed cell death. They are named caspases due to their specific cysteine protease activity – a cysteine in its active site nucleophilically attacks and cleaves a target protein only after an aspartic acid residue. As of 2009, there are 12 confirmed caspases in humans and 10 in mice, carrying out a variety of cellular functions.
Toll-like receptors (TLRs) are a class of proteins that play a key role in the innate immune system. They are single-pass membrane-spanning receptors usually expressed on sentinel cells such as macrophages and dendritic cells, that recognize structurally conserved molecules derived from microbes. Once these microbes have breached physical barriers such as the skin or intestinal tract mucosa, they are recognized by TLRs, which activate immune cell responses. The TLRs include TLR1, TLR2, TLR3, TLR4, TLR5, TLR6, TLR7, TLR8, TLR9, TLR10, TLR11, TLR12, and TLR13. Humans lack genes for TLR11, TLR12 and TLR13 and mice lack a functional gene for TLR10. TLR1, TLR2, TLR4, TLR5, TLR6, and TLR10 are located on the cell membrane, whereas TLR3, TLR7, TLR8, and TLR9 are located in intracellular vesicles.
The adaptive immune system, also known as the acquired immune system, is a subsystem of the immune system that is composed of specialized, systemic cells and processes that eliminate pathogens or prevent their growth. The acquired immune system is one of the two main immunity strategies found in vertebrates.
Pattern recognition receptors (PRRs) play a crucial role in the proper function of the innate immune system. PRRs are germline-encoded host sensors, which detect molecules typical for the pathogens. They are proteins expressed, mainly, by cells of the innate immune system, such as dendritic cells, macrophages, monocytes, neutrophils and epithelial cells, to identify two classes of molecules: pathogen-associated molecular patterns (PAMPs), which are associated with microbial pathogens, and damage-associated molecular patterns (DAMPs), which are associated with components of host's cells that are released during cell damage or death. They are also called primitive pattern recognition receptors because they evolved before other parts of the immune system, particularly before adaptive immunity. PRRs also mediate the initiation of antigen-specific adaptive immune response and release of inflammatory cytokines.
In cell biology, a phagosome is a vesicle formed around a particle engulfed by a phagocyte via phagocytosis. Professional phagocytes include macrophages, neutrophils, and dendritic cells (DCs).
The innate, or nonspecific, immune system is one of the two main immunity strategies in vertebrates. The innate immune system is an older evolutionary defense strategy, relatively speaking, and is the dominant immune system response found in plants, fungi, insects, and primitive multicellular organisms.
Lipid signaling, broadly defined, refers to any biological signaling event involving a lipid messenger that binds a protein target, such as a receptor, kinase or phosphatase, which in turn mediate the effects of these lipids on specific cellular responses. Lipid signaling is thought to be qualitatively different from other classical signaling paradigms because lipids can freely diffuse through membranes. One consequence of this is that lipid messengers cannot be stored in vesicles prior to release and so are often biosynthesized "on demand" at their intended site of action. As such, many lipid signaling molecules cannot circulate freely in solution but, rather, exist bound to special carrier proteins in serum.
Collectins (collagen-containing C-type lectins) are a part of the innate immune system. They form a family of collagenous Ca2+-dependent defense lectins, which are found in animals. Collectins are soluble pattern recognition receptors (PRRs). Their function is to bind to oligosaccharide structure or lipids that are on the surface of microorganisms. Like other PRRs they bind pathogen-associated molecular patterns (PAMPs) and danger-associated molecular patterns (DAMPs) of oligosaccharide origin. Binding of collectins to microorganisms may trigger elimination of microorganisms by aggregation, complement activation, opsonization, activation of phagocytosis, or inhibition of microbial growth. Other functions of collectins are modulation of inflammatory, allergic responses, adaptive immune system and clearance of apoptotic cells.
Macrophage migration inhibitory factor (MIF), also known as glycosylation-inhibiting factor (GIF), L-dopachrome isomerase, or phenylpyruvate tautomerase is a protein that in humans is encoded by the MIF gene. MIF is an important regulator of innate immunity. The MIF protein superfamily also includes a second member with functionally related properties, the D-dopachrome tautomerase (D-DT). CD74 is a surface receptor for MIF.
Receptor-interacting serine/threonine-protein kinase 2 is an enzyme that in humans is encoded by the RIPK2 gene.
Peptidoglycan recognition protein 2(PGLYRP2) is an enzyme, N-acetylmuramoyl-L-alanine amidase (NAMLAA), that hydrolyzes bacterial cell wall peptidoglycan and is encoded by the PGLYRP2 gene.
Caspase recruitment domain-containing protein 9 is an adaptor protein of the CARD-CC protein family, which in humans is encoded by the CARD9 gene. It mediates signals from pattern recognition receptors to activate pro-inflammatory and anti-inflammatory cytokines, regulating inflammation and cell apoptosis. Homozygous mutations in CARD9 are associated with defective innate immunity against yeasts, like Candida and dermatophytes.
Inflammasomes are cytosolic multiprotein oligomers of the innate immune system responsible for the activation of inflammatory responses. Activation and assembly of the inflammasome promotes proteolytic cleavage, maturation and secretion of pro-inflammatory cytokines interleukin 1β (IL-1β) and interleukin 18 (IL-18), as well as cleavage of Gasdermin-D. The N-terminal fragment resulting from this cleavage induces a pro-inflammatory form of programmed cell death distinct from apoptosis, referred to as pyroptosis, and is responsible for secretion of the mature cytokines, presumably through the formation of pores in the plasma membrane.
Peptidoglycan recognition proteins (PGRPs) are a group of highly conserved pattern recognition receptors with at least one peptidoglycan recognition domain capable of recognizing the peptidoglycan component of the cell wall of bacteria. They are present in insects, mollusks, echinoderms and chordates. The mechanism of action of PGRPs varies between taxa. In insects, PGRPs kill bacteria indirectly by activating one of four unique effector pathways: prophenoloxidase cascade, Toll pathway, IMD pathway, and induction of phagocytosis. In mammals, PGRPs either kill bacteria directly by interacting with their cell wall or outer membrane, or hydrolyze peptidoglycan. They also modulate inflammation and microbiome and interact with host receptors.
Phenoloxidase system is a major defense system in many invertebrates which ultimately leads to melanization of pathogens and damaged tissues. The process of melanization depends on activation of the enzyme phenoloxidase (PO) which is controlled by the prophenoloxidase (proPO) activation system.
Vishva Mitra Dixit is a physician of Indian origin who is the current Vice President of Discovery Research at Genentech.
Autoinflammatory diseases (AIDs) are a group of rare disorders caused by a dysfunction of the innate immune system.They are characterised by a perdiodic or chronic systemic inflammation usually without the involvement of adaptive immunity.
