Douglas Fearon

Last updated

Douglas Fearon
Born
Douglas Thomas Fearon

(1942-10-16) 16 October 1942 (age 82) [1]
Alma mater
Awards
Scientific career
Fields Immunology
Website www.cshl.edu/Faculty/Douglas-Fearon.html

Douglas Thomas Fearon (born 16 October 1942) [1] [2] is an American medical immunologist, who has been since 2003 Sheila Joan Smith Professor of Immunology at the University of Cambridge, a fellow of Trinity College, Cambridge, and a professor at Cold Spring Harbor Laboratory. [3] [4] [5] [6] [7]

Awards and honours

Fearon was elected a Fellow of the Royal Society (FRS) in 1999 and is also member of the United States National Academy of Sciences. [3] His nomination for the Royal Society reads:

The research of Douglas T. Fearon has helped establish a unifying principle in immunology; namely, that the two systems of immunity, innate and acquired, are integrated. The former identifies antigens of microbial origin to bias the response of the latter to those antigens. To support this thesis, he has 1) determined how the alternative complement pathway of innate immunity attaches C3 to microbial antigens; 2) demonstrated that the attached C3 causes antigen to be orders of magnitude more potent in eliciting an acquired immune response; and 3) characterised the CR2/CD19 receptor complex of B lymphocytes that mediates the enhanced immunogenicity of C3-bearing antigens, and the counter-regulatory coreceptor, CD22, that suppresses the cellular response to antigen. [8]

Related Research Articles

<span class="mw-page-title-main">Antigen</span> Molecule triggering an immune response (antibody production) in the host

In immunology, an antigen (Ag) is a molecule, moiety, foreign particulate matter, or an allergen, such as pollen, that can bind to a specific antibody or T-cell receptor. The presence of antigens in the body may trigger an immune response.

<span class="mw-page-title-main">Immune system</span> Biological system protecting an organism against disease

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.

<span class="mw-page-title-main">Immunology</span> Branch of medicine studying the immune system

Immunology is a branch of biology and medicine that covers the study of immune systems in all organisms.

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.

Humoral immunity is the aspect of immunity that is mediated by macromolecules – including secreted antibodies, complement proteins, and certain antimicrobial peptides – located in extracellular fluids. Humoral immunity is named so because it involves substances found in the humors, or body fluids. It contrasts with cell-mediated immunity. Humoral immunity is also referred to as antibody-mediated immunity.

<span class="mw-page-title-main">Complement system</span> Part of the immune system that enhances the ability of antibodies and phagocytic cells

The complement system, also known as complement cascade, is a part of the humoral, innate immune system and enhances (complements) the ability of antibodies and phagocytic cells to clear microbes and damaged cells from an organism, promote inflammation, and attack the pathogen's cell membrane. Despite being part of the innate immune system, the complement system can be recruited and brought into action by antibodies generated by the adaptive immune system.

<span class="mw-page-title-main">Classical complement pathway</span> Aspect of the immune system

The classical complement pathway is one of three pathways which activate the complement system, which is part of the immune system. The classical complement pathway is initiated by antigen-antibody complexes with the antibody isotypes IgG and IgM.

Opsonins are extracellular proteins that, when bound to substances or cells, induce phagocytes to phagocytose the substances or cells with the opsonins bound. Thus, opsonins act as tags to label things in the body that should be phagocytosed by phagocytes. Different types of things ("targets") can be tagged by opsonins for phagocytosis, including: pathogens, cancer cells, aged cells, dead or dying cells, excess synapses, or protein aggregates. Opsonins help clear pathogens, as well as dead, dying and diseased cells.

Pathogen-associated molecular patterns (PAMPs) are small molecular motifs conserved within a class of microbes, but not present in the host. They are recognized by toll-like receptors (TLRs) and other pattern recognition receptors (PRRs) in both plants and animals. This allows the innate immune system to recognize pathogens and thus, protect the host from infection.

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, as well as by 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.

<span class="mw-page-title-main">Innate immune system</span> Immunity strategy in living beings

The innate immune system or nonspecific immune system is one of the two main immunity strategies in vertebrates. The innate immune system is an alternate defense strategy and is the dominant immune system response found in plants, fungi, prokaryotes, and invertebrates.

<span class="mw-page-title-main">CD19</span> Biomarker for B cell lineage

B-lymphocyte antigen CD19, also known as CD19 molecule, B-Lymphocyte Surface Antigen B4, T-Cell Surface Antigen Leu-12 and CVID3 is a transmembrane protein that in humans is encoded by the gene CD19. In humans, CD19 is expressed in all B lineage cells. Contrary to some early doubts, human plasma cells do express CD19. CD19 plays two major roles in human B cells: on the one hand, it acts as an adaptor protein to recruit cytoplasmic signaling proteins to the membrane; on the other, it works within the CD19/CD21 complex to decrease the threshold for B cell receptor signaling pathways. Due to its presence on all B cells, it is a biomarker for B lymphocyte development, lymphoma diagnosis and can be utilized as a target for leukemia immunotherapies.

<span class="mw-page-title-main">C3b</span>

C3b is the larger of two elements formed by the cleavage of complement component 3, and is considered an important part of the innate immune system. C3b is potent in opsonization: tagging pathogens, immune complexes (antigen-antibody), and apoptotic cells for phagocytosis. Additionally, C3b plays a role in forming a C3 convertase when bound to Factor B, or a C5 convertase when bound to C4b and C2b or when an additional C3b molecule binds to the C3bBb complex.

<span class="mw-page-title-main">C-C chemokine receptor type 6</span> Mammalian protein found in Homo sapiens

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.

<span class="mw-page-title-main">C3a (complement)</span>

C3a is one of the proteins formed by the cleavage of complement component 3; the other is C3b. C3a is a 77 residue anaphylatoxin that binds to the C3a receptor (C3aR), a class A G protein-coupled receptor. It plays a large role in the immune response.

<span class="mw-page-title-main">Mucosal immunology</span> Field of study

Mucosal immunology is the study of immune system responses that occur at mucosal membranes of the intestines, the urogenital tract, and the respiratory system. The mucous membranes are in constant contact with microorganisms, food, and inhaled antigens. In healthy states, the mucosal immune system protects the organism against infectious pathogens and maintains a tolerance towards non-harmful commensal microbes and benign environmental substances. Disruption of this balance between tolerance and deprivation of pathogens can lead to pathological conditions such as food allergies, irritable bowel syndrome, susceptibility to infections, and more.

Mucosal-associated invariant T cells make up a subset of T cells in the immune system that display innate, effector-like qualities. In humans, MAIT cells are found in the blood, liver, lungs, and mucosa, defending against microbial activity and infection. The MHC class I-like protein, MR1, is responsible for presenting bacterially-produced vitamin B2 and B9 metabolites to MAIT cells. After the presentation of foreign antigen by MR1, MAIT cells secrete pro-inflammatory cytokines and are capable of lysing bacterially-infected cells. MAIT cells can also be activated through MR1-independent signaling. In addition to possessing innate-like functions, this T cell subset supports the adaptive immune response and has a memory-like phenotype. Furthermore, MAIT cells are thought to play a role in autoimmune diseases, such as multiple sclerosis, arthritis and inflammatory bowel disease, although definitive evidence is yet to be published.

David Arthur Tuveson is an American cancer biologist and is currently Roy J. Zuckerberg Professor of Cancer Research as well as The Cancer Center Director at Cold Spring Harbor Laboratory. Dr. Tuveson is also the Chief Scientist for the Lustgarten Foundation for Pancreatic Cancer Research. He is known for developing some of the first mouse models of pancreatic cancer and more recently, for his work developing pancreatic cancer organoids.

<span class="mw-page-title-main">Type 3 innate lymphoid cells</span>

Type 3 innate lymphoid cells (ILC3) are immune cells from the lymphoid lineage that are part of the innate immune system. These cells participate in innate mechanisms on mucous membranes, contributing to tissue homeostasis, host-commensal mutualism and pathogen clearance. They are part of a heterogeneous group of innate lymphoid cells, which is traditionally divided into three subsets based on their expression of master transcription factors as well as secreted effector cytokines - ILC1, ILC2 and ILC3.

Mitchell Kronenberg is an American immunologist and the chief scientific officer at La Jolla Institute for Immunology. He served as president of the institute from 2003 to 2021. 

References

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  3. 1 2 Nuzzo, R. (2005). "Biography of Douglas T. Fearon". Proceedings of the National Academy of Sciences . 102 (21): 7415–7417. doi: 10.1073/pnas.0502415102 . PMC   1140442 . PMID   15899974.
  4. Feig, C; Jones, J. O.; Kraman, M; Wells, R. J.; Deonarine, A; Chan, D. S.; Connell, C. M.; Roberts, E. W.; Zhao, Q; Caballero, O. L.; Teichmann, S. A.; Janowitz, T; Jodrell, D. I.; Tuveson, D. A.; Fearon, D. T. (2013). "Targeting CXCL12 from FAP-expressing carcinoma-associated fibroblasts synergizes with anti-PD-L1 immunotherapy in pancreatic cancer". Proceedings of the National Academy of Sciences. 110 (50): 20212–7. Bibcode:2013PNAS..11020212F. doi: 10.1073/pnas.1320318110 . PMC   3864274 . PMID   24277834.
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  6. Fearon, D. T.; Locksley, R. M. (1996). "The instructive role of innate immunity in the acquired immune response". Science. 272 (5258): 50–3. Bibcode:1996Sci...272...50F. doi:10.1126/science.272.5258.50. PMID   8600536. S2CID   21383755.
  7. "Douglas Fearon". Cold Spring Harbor Laboratory. Retrieved 30 April 2020.
  8. "EC/1999/15: Fearon, Douglas Thomas". London: The Royal Society. Archived from the original on 6 April 2015. Retrieved 5 April 2015.