Judi Allen | |
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Born | Judith Elizabeth Allen |
Alma mater | Bates College University of California, Berkeley |
Awards | EMBO Member (2018) [1] |
Scientific career | |
Institutions | University of Manchester Imperial College London University of Edinburgh |
Thesis | The cysteine-rich proteins of Chlamydia trachomatis in structure and immunity (1991) |
Website | research |
Judith Elizabeth Allen FRS FMedSci FRSE FRSB is a British scientist who is Professor of Immunobiology at the University of Manchester. [2] [3] She is an expert on macrophages activated during helminthiasis and was elected Fellow of the Royal Society (FRS) in 2023. She has also done extensive work into type 2 immunity and was awarded Honorary Professor at the University of Edinburgh in 2016. [4]
Allen earned her undergraduate degree at Bates College. [5] She was a doctoral researcher at the University of California, Berkeley, [5] where her PhD investigated cysteine-rich proteins of Chlamydia trachomatis . [6]
Allen spent several years in the biotechnology sector before joining Imperial College London as a postdoctoral researcher. [5] In 1997, she was awarded a fellowship from the Medical Research Council and moved to the University of Edinburgh. She was made Professor of Immunobiology there in 2005. [7]
Allen studies helminthiasis, a disease caused by helminth (parasitic worm) infection. The infection is associated with the induction of a type 2 immune response in mammals. Allen has identified macrophages with a specific type 2 expression profile, which are found both at the site of the infection and in injured tissue. The macrophage phenotype is influenced by the genotype of the host and the infected site. Allen discovered a relationship between the chitinase-like protein 3 YM1 and Interleukin 17, an inflammatory cytokine associated with autoimmune disease. [8] [9]
Judi Allen has also completed some research explaining the relationship between a type 2 cytokine Interleukin 13, IL-13, and SARS-Cov-2 infection, better known as COVID-19. SARS-Cov-2 is a virus that affects the respiratory system and patients exhibit higher levels of inflammatory cytokines in response to infection. Allen helped discover that IL-13 encourages SARS-Cov-2 to progress in severity through the increased accumulation of hyaluronan polysaccharide (HA) in the lungs. In her study, Allen discovered Interleukin 13 neutralization resulted in a decrease in the amount of HA in the lungs and a decrease in the severity of the disease. [10]
Allen then went on to join the University of Manchester faculty in 2016. [11]
Allen also published a paper in 2023 concerning T helper 2 cells and nematode infection. Allen used mice with different immune genotypes to measure the different immune responses to Litomosoides sigmodontis, a nematode that infects the pleural cavity. Th2 cells, T helper 2, controlled the cell’s pathway of the tissue-resident macrophages from monocytes which affected the infection response. C57BL/6 mice had a strong conversion to large cavity macrophage from the monocyte while BALB/c mice had a weak conversion. Therefore, Allen has made an impact in the adaptive immune response component of cells in immunobiology. [12]
Judi Allen has helped to establish a relationship between the extracellular matrix in organisms and the immune system. The matrix and the immune system must work together to fight any infection or disease in organisms. There are many molecules and relationships that contribute to this working partnership. For example, the immune system will regulate the extracellular matrix through chemokines or cytokines, inflammatory signals, which will call for leukocyte extravasation to an injury site. Interleukin 13, a type 2 cytokine Allen has worked with previously, not only regulates hyaluronan polysaccharide but also mucus which is an important structure in the extracellular matrix as well. Allen has also emphasized the importance this relationship has for potential new immunotherapies. [13]
An immune response is a physiological reaction which occurs within an organism in the context of inflammation for the purpose of defending against exogenous factors. These include a wide variety of different toxins, viruses, intra- and extracellular bacteria, protozoa, helminths, and fungi which could cause serious problems to the health of the host organism if not cleared from the body.
Cytokines are a broad and loose category of small proteins important in cell signaling. Due to their size, cytokines cannot cross the lipid bilayer of cells to enter the cytoplasm and therefore typically exert their functions by interacting with specific cytokine receptors on the target cell surface. Cytokines have been shown to be involved in autocrine, paracrine and endocrine signaling as immunomodulating agents.
Macrophages are a type of white blood cell of the innate immune system that engulf and digest pathogens, such as cancer cells, microbes, cellular debris, and foreign substances, which do not have proteins that are specific to healthy body cells on their surface. This process is called phagocytosis, which acts to defend the host against infection and injury.
The T helper cells (Th cells), also known as CD4+ cells or CD4-positive cells, are a type of T cell that play an important role in the adaptive immune system. They aid the activity of other immune cells by releasing cytokines. They are considered essential in B cell antibody class switching, breaking cross-tolerance in dendritic cells, in the activation and growth of cytotoxic T cells, and in maximizing bactericidal activity of phagocytes such as macrophages and neutrophils. CD4+ cells are mature Th cells that express the surface protein CD4. Genetic variation in regulatory elements expressed by CD4+ cells determines susceptibility to a broad class of autoimmune diseases.
Phagocytes are cells that protect the body by ingesting harmful foreign particles, bacteria, and dead or dying cells. Their name comes from the Greek phagein, "to eat" or "devour", and "-cyte", the suffix in biology denoting "cell", from the Greek kutos, "hollow vessel". They are essential for fighting infections and for subsequent immunity. Phagocytes are important throughout the animal kingdom and are highly developed within vertebrates. One litre of human blood contains about six billion phagocytes. They were discovered in 1882 by Ilya Ilyich Mechnikov while he was studying starfish larvae. Mechnikov was awarded the 1908 Nobel Prize in Physiology or Medicine for his discovery. Phagocytes occur in many species; some amoebae behave like macrophage phagocytes, which suggests that phagocytes appeared early in the evolution of life.
Monocytes are a type of leukocyte or white blood cell. They are the largest type of leukocyte in blood and can differentiate into macrophages and monocyte-derived dendritic cells. As a part of the vertebrate innate immune system monocytes also influence adaptive immune responses and exert tissue repair functions. There are at least three subclasses of monocytes in human blood based on their phenotypic receptors.
Kupffer cells, also known as stellate macrophages and Kupffer–Browicz cells, are specialized cells localized in the liver within the lumen of the liver sinusoids and are adhesive to their endothelial cells which make up the blood vessel walls. Kupffer cells comprise the largest population of tissue-resident macrophages in the body. Gut bacteria, bacterial endotoxins, and microbial debris transported to the liver from the gastrointestinal tract via the portal vein will first come in contact with Kupffer cells, the first immune cells in the liver. It is because of this that any change to Kupffer cell functions can be connected to various liver diseases such as alcoholic liver disease, viral hepatitis, intrahepatic cholestasis, steatohepatitis, activation or rejection of the liver during liver transplantation and liver fibrosis. They form part of the mononuclear phagocyte system.
Chemokines, or chemotactic cytokines, are a family of small cytokines or signaling proteins secreted by cells that induce directional movement of leukocytes, as well as other cell types, including endothelial and epithelial cells. In addition to playing a major role in the activation of host immune responses, chemokines are important for biological processes, including morphogenesis and wound healing, as well as in the pathogenesis of diseases like cancers.
Granulocyte-macrophage colony-stimulating factor (GM-CSF), also known as colony-stimulating factor 2 (CSF2), is a monomeric glycoprotein secreted by macrophages, T cells, mast cells, natural killer cells, endothelial cells and fibroblasts that functions as a cytokine. The pharmaceutical analogs of naturally occurring GM-CSF are called sargramostim and molgramostim.
Interleukin 8 is a chemokine produced by macrophages and other cell types such as epithelial cells, airway smooth muscle cells and endothelial cells. Endothelial cells store IL-8 in their storage vesicles, the Weibel-Palade bodies. In humans, the interleukin-8 protein is encoded by the CXCL8 gene. IL-8 is initially produced as a precursor peptide of 99 amino acids which then undergoes cleavage to create several active IL-8 isoforms. In culture, a 72 amino acid peptide is the major form secreted by macrophages.
Macrophage Inflammatory Proteins (MIP) belong to the family of chemotactic cytokines known as chemokines. In humans, there are two major forms, MIP-1α and MIP-1β, renamed CCL3 and CCL4 respectively, since 2000. However, other names are sometimes encountered in older literature, such as LD78α, AT 464.1 and GOS19-1 for human CCL3 and AT 744, Act-2, LAG-1, HC21 and G-26 for human CCL4. Other macrophage inflammatory proteins include MIP-2, MIP-3 and MIP-5.
Monoblasts are the committed progenitor cells that differentiated from a committed macrophage or dendritic cell precursor (MDP) in the process of hematopoiesis. They are the first developmental stage in the monocyte series leading to a macrophage. Their myeloid cell fate is induced by the concentration of cytokines they are surrounded by during development. These cytokines induce the activation of transcription factors which push completion of the monoblast's myeloid cell fate. Monoblasts are normally found in bone marrow and do not appear in the normal peripheral blood. They mature into monocytes which, in turn, develop into macrophages. They then are seen as macrophages in the normal peripheral blood and many different tissues of the body. Macrophages can produce a variety of effector molecules that initiate local, systemic inflammatory responses. These monoblast differentiated cells are equipped to fight off foreign invaders using pattern recognition receptors to detect antigen as part of the innate immune response.
Interleukin 32 (IL32) is proinflammatory cytokine that in humans is encoded by the IL32 gene. Interleukin 32 can be found in higher mammals but not in rodents. It is mainly expressed intracellularly and the protein has nine different isoforms, because the pre-mRNA can be alternatively spliced. The most active and studied isoform is IL-32γ. It was first reported in 2005, although the IL-32 gene was first described in 1992. It does not belong to any cytokine family because there is almost no homology with other cytokines.
Interleukin 19 (IL-19) is an immunosuppressive protein that belongs to the IL-10 cytokine subfamily.
An alveolar macrophage, pulmonary macrophage, is a type of macrophage, a professional phagocyte, found in the airways and at the level of the alveoli in the lungs, but separated from their walls.
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 macrophage-activating factor (MAF) is a lymphokine or other receptor based signal that primes macrophages towards cytotoxicity to tumors, cytokine secretion, or clearance of pathogens. Similar molecules may cause development of an inhibitory, regulatory phenotype. A MAF can also alter the ability of macrophages to present MHC I antigen, participate in Th responses, and/or affect other immune responses.
The Interleukin-1 family is a group of 11 cytokines that plays a central role in the regulation of immune and inflammatory responses to infections or sterile insults.
The IL-10 family is a family of interleukins.
Interleukin 17F (IL-17F) is signaling protein that is in human is encoded by the IL17F gene and is considered a pro-inflammatory cytokine. This protein belongs to the interleukin 17 family and is mainly produced by the T helper 17 cells after their stimulation with interleukin 23. However, IL-17F can be also produced by a wide range of cell types, including innate immune cells and epithelial cells.