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Dendritic cells (DCs) are antigen-presenting cells of the mammalian immune system. Their main function is to process antigen material and present it on the cell surface to the T cells of the immune system. They act as messengers between the innate and the adaptive immune systems.
Immunotherapy or biological therapy is the treatment of disease by activating or suppressing the immune system. Immunotherapies designed to elicit or amplify an immune response are classified as activation immunotherapies, while immunotherapies that reduce or suppress are classified as suppression immunotherapies. Immunotherapy is under preliminary research for its potential to treat various forms of cancer.
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.
Interleukin-15 (IL-15) is a protein that in humans is encoded by the IL15 gene. IL-15 is an inflammatory cytokine with structural similarity to Interleukin-2 (IL-2). Like IL-2, IL-15 binds to and signals through a complex composed of IL-2/IL-15 receptor beta chain (CD122) and the common gamma chain. IL-15 is secreted by mononuclear phagocytes following infection by virus(es). This cytokine induces the proliferation of natural killer cells, i.e. cells of the innate immune system whose principal role is to kill virally infected cells.
Cluster of Differentiation 86 is a protein constitutively expressed on dendritic cells, Langerhans cells, macrophages, B-cells, and on other antigen-presenting cells. Along with CD80, CD86 provides costimulatory signals necessary for T cell activation and survival. Depending on the ligand bound, CD86 can signal for self-regulation and cell-cell association, or for attenuation of regulation and cell-cell disassociation.
Interleukin-22 receptor subunit alpha-2 (IL-22RA2), also known as interleukin-22 binding protein (IL-22BP) is a naturally secreted monomeric protein acting as an interleukin-22 (IL-22) antagonist with inhibitory effects on IL-22 activity in vivo. IL-22BP is in humans encoded by the IL22RA2 gene located on chromosome 6, and in mice is encoded by the il22ra2 gene located on chromosome 10. IL-22BP belongs to the class II cytokine receptor family and it is a soluble receptor homolog of IL-22R.
In immunology, peripheral tolerance is the second branch of immunological tolerance, after central tolerance. It takes place in the immune periphery. Its main purpose is to ensure that self-reactive T and B cells which escaped central tolerance do not cause autoimmune disease. Peripheral tolerance prevents immune response to harmless food antigens and allergens, too.
Chemokine receptor 6 also known as CCR6 is a CC chemokine receptor protein which in humans is encoded by the CCR6 gene. CCR6 has also recently been designated CD196. The gene is located on the long arm of Chromosome 6 (6q27) on the Watson (plus) strand. It is 139,737 bases long and encodes a protein of 374 amino acids.
CD83 is a human protein encoded by the CD83 gene.
ICOS ligand is a protein that in humans is encoded by the ICOSLG gene located at chromosome 21. ICOSLG has also been designated as CD275.
Programmed cell death 1 ligand 2 is a protein that in humans is encoded by the PDCD1LG2 gene. PDCD1LG2 has also been designated as CD273. PDCD1LG2 is an immune checkpoint receptor ligand which plays a role in negative regulation of the adaptive immune response. PD-L2 is one of two known ligands for Programmed cell death protein 1 (PD-1).
Lymphocyte-activation gene 3, also known as LAG-3, is a protein which in humans is encoded by the LAG3 gene. LAG3, which was discovered in 1990 and was designated CD223 after the Seventh Human Leucocyte Differentiation Antigen Workshop in 2000, is a cell surface molecule with diverse biologic effects on T cell function. It is an immune checkpoint receptor and as such is the target of various drug development programs by pharmaceutical companies seeking to develop new treatments for cancer and autoimmune disorders. In soluble form it is also being developed as a cancer drug in its own right.
Thymic stromal lymphopoietin (TSLP) is a protein belonging to the cytokine family. It is known to play an important role in the maturation of T cell populations through activation of antigen-presenting cells.
Interleukin-17A is a protein that in humans is encoded by the IL17A gene. In rodents, IL-17A used to be referred to as CTLA8, after the similarity with a viral gene.
Interleukin 23 (IL-23) is a heterodimeric cytokine composed of an IL-12B (IL-12p40) subunit and an IL-23A (IL-23p19) subunit. IL-23 is part of the IL-12 family of cytokines. The functional receptor for IL-23 consists of a heterodimer between IL-12Rβ1 and IL-23R.
Gabrielle T. Belz is an Australian molecular immunologist and viral immunologist. She is a faculty member of the Walter and Eliza Hall Institute of Medical Research, within the Molecular Immunology division. Belz has made important contributions to the understanding of immune system function, especially in relation to the molecular and cellular signalling pathways of immune response to viruses. Her research has focused on understanding the signals that drive the initial development of protective immunity against pathogen infections, such as influenza and herpes viruses. This includes research into how cytotoxic T cells recognise and remove virally-infected cells from the body following infection. Research into the description of the specific factors and response during infection will contribute towards the long-term development of vaccines for infectious disease, and the development of better treatments for autoimmune diseases.
Tolerogenic therapy aims to induce immune tolerance where there is pathological or undesirable activation of the normal immune response. This can occur, for example, when an allogeneic transplantation patient develops an immune reaction to donor antigens, or when the body responds inappropriately to self antigens implicated in autoimmune diseases. It must provide absence of specific antibodies for exactly that antigenes.
Tolerogenic dendritic cells are heterogenous pool of dendritic cells with immuno-suppressive properties, priming immune system into tolerogenic state against various antigens. These tolerogenic effects are mostly mediated through regulation of T cells such as inducing T cell anergy, T cell apoptosis and induction of Tregs. Tol-DCs also affect local micro-environment toward tolerogenic state by producing anti-inflammatory cytokines.
Jean Sylvia Marshall, born in Birmingham, England, is a Canadian immunologist and acting Professor and Head of the Department of Microbiology & Immunology at Dalhousie University in Halifax, Nova Scotia, Canada. Marshall's work has investigated how mast cells are involved in the early immune response to infection and antigen. She is best known for her discovery of the previously unknown degranulation-independent immunoregulatory roles of mast cells in infection and allergy and their ability to mobilize dendritic cells.
Graham Stephen Le Gros is a New Zealand immunologist. He is currently Director of the Malaghan Institute of Medical Research in Wellington, New Zealand and leads its Allergic and Parasitic Diseases Programme. He is also Research Director of the Vaccine Alliance Aotearoa New Zealand – Ohu Kaupare Huaketo and a Research Professor at Victoria University of Wellington.
References
- ↑ Sika-Paotonu, Dianne (1 January 2014). Increasing the potency of dendritic cell based vaccines for the treatment of cancer (Doctoral thesis). Open Access Te Herenga Waka-Victoria University of Wellington.
- 1 2 "Professor Franca Ronchese". Malaghan. Retrieved 31 January 2018.
- ↑ "Professor Franca Ronchese | Health Research Council". Hrc.govt.nz. Retrieved 31 January 2018.
- ↑ "Franca Ronchese - The latest science on allergic reactions". RNZ. 4 August 2018. Retrieved 19 October 2020.
- ↑ "New Zealand scientific breakthrough could provide new allergy, asthma treatments". The New Zealand Herald . 25 January 2018. Retrieved 31 January 2018.
- ↑ "City scientists patent asthma breakthrough". Stuff.co.nz. 6 October 2014. Retrieved 31 January 2018.
- ↑ Professor Franca Ronchese. "Is Franca Ronchese the NEXT Woman of the Year 2012?". Malaghan. Retrieved 31 January 2018.
- ↑ Media, Gloss Creative. "The Burnet Oration | Australian and New Zealand Society for Immunology | The premier scientific society for Immunology research in Australia and New Zealand". www.immunology.org.au. Retrieved 19 October 2020.
- ↑ "Finding a cancer cure is his holy grail". Stuff.co.nz. 2 June 2014. Retrieved 31 January 2018.
