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Natural killer cells, also known as NK cells or large granular lymphocytes (LGL), are a type of cytotoxic lymphocyte critical to the innate immune system. They 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 cell and other intracellular pathogens acting at around 3 days after infection, and respond to tumor formation. Most immune cells detect the antigen presented on major histocompatibility complex (MHC) 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 missing "self" markers of MHC class I. This role is especially important because harmful cells that are missing MHC I markers cannot be detected and destroyed by other immune cells, such as T lymphocyte cells.
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.
Systems immunology is a research field under systems biology that uses mathematical approaches and computational methods to examine the interactions within cellular and molecular networks of the immune system. The immune system has been thoroughly analyzed as regards to its components and function by using a "reductionist" approach, but its overall function can't be easily predicted by studying the characteristics of its isolated components because they strongly rely on the interactions among these numerous constituents. It focuses on in silico experiments rather than in vivo.
The Cluster of differentiation 80 is a B7, type I membrane protein in the immunoglobulin superfamily, with an extracellular immunoglobulin constant-like domain and a variable-like domain required for receptor binding. It is closely related to CD86, another B7 protein (B7-2), and often works in tandem. Both CD80 and CD86 interact with costimulatory receptors CD28, CTLA-4 (CD152) and the p75 neurotrophin receptor.
CD94, also known as killer cell lectin-like receptor subfamily D, member 1 (KLRD1) is a human gene.
CD16, also known as FcγRIII, is a cluster of differentiation molecule found on the surface of natural killer cells, neutrophils, monocytes, macrophages, and certain T cells. CD16 has been identified as Fc receptors FcγRIIIa (CD16a) and FcγRIIIb (CD16b), which participate in signal transduction. The most well-researched membrane receptor implicated in triggering lysis by NK cells, CD16 is a molecule of the immunoglobulin superfamily (IgSF) involved in antibody-dependent cellular cytotoxicity (ADCC). It can be used to isolate populations of specific immune cells through fluorescent-activated cell sorting (FACS) or magnetic-activated cell sorting, using antibodies directed towards CD16.
CD244 also known as 2B4 or SLAMF4 is a protein that in humans is encoded by the CD244 gene.
Killer cell immunoglobulin-like receptor 2DL1 is a protein that in humans is encoded by the KIR2DL1 gene.
NKG2-C type II integral membrane protein or NKG2C is a protein that in humans is encoded by the KLRC2 gene. It is also known as or cluster of differentiation 159c (CD159c).
Interleukin-28 receptor is a type II cytokine receptor found largely in epithelial cells. It binds type 3 interferons, interleukin-28 A, Interleukin-28B, interleukin 29 and interferon lambda 4. It consists of an α chain and shares a common β subunit with the interleukin-10 receptor. Binding to the interleukin-28 receptor, which is restricted to select cell types, is important for fighting infection. Binding of the type 3 interferons to the receptor results in activation of the JAK/STAT signaling pathway.
A tunneling nanotube(TNT) or membrane nanotube is a term that has been applied to cytoskeletal protrusions that extend from the plasma membrane which enable different animal cells to connect over long distances, sometimes over 100 μm between certain types of cells. Tunneling nanotubes that are less than 0.7 micrometers in diameter, have an actin structure and carry portions of plasma membrane between cells in both directions. Larger TNTs (>0.7 μm) contain an actin structure with microtubules and/or intermediate filaments, and can carry components such as vesicles and organelles between cells, including whole mitochondria. The diameter of TNTs ranges from 0.05 μm to 1.5 μm and they can reach lengths of several cell diameters. There have been two types of observed TNTs: open ended and closed ended. Open ended TNTs connect the cytoplasm of two cells. Closed ended TNTs do not have continuous cytoplasm as there is a gap junction cap that only allows small molecules and ions to flow between cells. These structures have shown involvement in cell-to-cell communication, transfer of nucleic acids such as mRNA and miRNA between cells in culture or in a tissue, and the spread of pathogens or toxins such as HIV and prions. TNTs have observed lifetimes ranging from a few minutes up to several hours, and several proteins have been implicated in their formation and inhibition, including many that interact with Arp2/3.
Jack Leonard Strominger is the Higgins Professor of Biochemistry at Harvard University, specializing in the structure and function of human histocompatibility proteins and their role in disease. He won the Albert Lasker Award for Basic Medical Research in 1995.
NKG2D is an activating receptor (transmembrane protein) belonging to the NKG2 family of C-type lectin-like receptors. NKG2D is encoded by KLRK1 (killer cell lectin like receptor K1) gene which is located in the NK-gene complex (NKC) situated on chromosome 6 in mice and chromosome 12 in humans. In mice, it is expressed by NK cells, NK1.1+ T cells, γδ T cells, activated CD8+ αβ T cells and activated macrophages. In humans, it is expressed by NK cells, γδ T cells and CD8+ αβ T cells. NKG2D recognizes induced-self proteins from MIC and RAET1/ULBP families which appear on the surface of stressed, malignant transformed, and infected cells.
Gillian Griffiths, FMedSci FRS is a British cell biologist and immunologist. Griffiths was one of the first to show that immune cells have specialised mechanisms of secretion, and identified proteins and mechanisms that control cytotoxic T lymphocyte secretion. Griffiths is Professor of Cell Biology and Immunology at the University of Cambridge and is the Director of the Cambridge Institute for Medical Research.
The Compatibility Gene is a 2013 book about the discovery of the mechanism of compatibility in the human immune system by the English professor of immunology, Daniel M. Davis. It describes the history of immunology with the discovery of the principle of graft rejection by Peter Medawar in the 1950s, and the way the body distinguishes self from not-self via natural killer cells. The compatibility mechanism contributes also to the success of pregnancy by helping the placenta to form, and may play a role in mate selection.
Sir Andrew James McMichael, is an immunologist, Professor of Molecular Medicine, and previously Director of the Weatherall Institute of Molecular Medicine at the University of Oxford. He is particularly known for his work on T cell responses to viral infections such as influenza and HIV.
Dawn M. E. Bowdish, is a Canadian immunologist and currently a professor in the Department of Pathology and Molecular Medicine at McMaster University in Ontario, Canada. She is a Tier 2 Canada Research Chair in Aging & Immunity. She is known for several discoveries including the immunomodulatory properties of the antimicrobial peptide LL-37, how MARCO signalling complex recognizes Mycobacterium tuberculosis, age-associated inflammation and its effects on clearing pneumococcal pneumonia and how the aging gut microbiome drives age-associated inflammation.
Misty Rayna Jenkins is an Australian scientist known for her research into lymphocytes and cancer treatment.
Uterine natural killer cells make up approximately 70% of maternal lymphocytes during pregnancy, occupying both the decidua basalis of the endometrium at the implantation site and the mesometrial lymphoid aggregate of pregnancy (MLAp) that surrounds the blood vessels supplying the placenta. This number is at its peak in early pregnancy but declines at parturition.
Catherine Blish is a translational immunologist and professor at Stanford University. Her lab works on clinical immunology and focuses primarily on the role of the innate immune system in fighting infectious diseases like HIV, dengue fever, and influenza. Her immune cell biology work characterizes the biology and action of Natural Killer (NK) cells and macrophages.
References
- ↑ "Professor Daniel Davis". Imperial College London. October 5, 2006. Retrieved September 16, 2022.
- ↑ "Daniel M Davis, University of Manchester".
- ↑ Infarinato, Nicole (2018). "Dan Davis: Up close and personal with immune cells". Journal of Cell Biology. 217 (9): 2975–2976. doi:10.1083/jcb.201808060. PMC 6122991 . PMID 30108126.
- ↑ "Daniel M. Davis" (PDF). University of Manchester. Archived from the original (PDF) on 6 March 2017. Retrieved 5 March 2017.
- ↑ "Professor Daniel Davis". Imperial College. Retrieved 5 March 2017.
- ↑ "Focus on Natural Killer Cells: Classics". Nature Immunology. 9 (5). 2008.
- ↑ "Fellow Professor Daniel Davis". The Academy of Medical Sciences. Archived from the original on 21 April 2019. Retrieved 5 March 2017.
- ↑ Davis DM, Chiu I, Fassett M, Cohen GB, Mandelboim O, Strominger JL (Dec 1999). "The human natural killer cell immune synapse". Proc Natl Acad Sci U S A. 96 (26): 15062–7. Bibcode:1999PNAS...9615062D. doi: 10.1073/pnas.96.26.15062 . PMC 24773 . PMID 10611338.
- ↑ Davis DM, Sowinski S (June 2008). "Membrane nanotubes: dynamic long-distance connections between animal cells". Nat. Rev. Mol. Cell Biol. 9 (6): 431–6. doi:10.1038/nrm2399. PMID 18431401. S2CID 8136865.
