C. Garrison Fathman is a Professor of Medicine and Division Chief of Immunology and Rheumatology at Stanford University School of Medicine. He is also the Associate Director of the Institute for Immunity, Transplantation and Infection and Director of the Center for Clinical Immunology at Stanford University. He was Founder and first-President of the Federation of Clinical Immunology Societies. [1] As Director of the CCIS, Dr. Fathman initiated a multidisciplinary approach to study and treat autoimmune diseases, including rheumatoid arthritis, multiple sclerosis, and insulin-dependent diabetes mellitus, and initiated several new approaches to education and community outreach. [2]
Dr. Fathman received his M.D. from Washington University School of Medicine 1969. He subsequently completed his residency training at Dartmouth Affiliated Hospitals and completed a fellowship in immunology and rheumatology at Stanford University. Fathman then spent four years doing research, first as a clinical associate at the National Cancer Institute of the NIH, and then as a member of the Basel Institute of Immunology in Switzerland. He returned to the United States to join the faculty at the Mayo Clinic Medical School in 1977 and was recruited back to Stanford University in 1981. [3]
Dr. Fathman has been and continues to be a leading figure in the field of clinical immunology. [2] His research centers on a molecular and cellular understanding of CD4 T cell responsiveness in mice and man. [4]
President of the Federation of Clinical immunology Societies: Distinguished Achievement in Clinical Investigation, Society of Investigative Dermatology; President of the Clinical immunology Society; Council of ACSI; Director JDRF Center of Excellence; director, NIH Autoimmunity Prevention Center; Director of the Center for Clinical immunology at Stanford; Associate Director, Institute of Immunity, Transplantation and Infection, Stanford Medical School; Co-Chairman of the Autoimmunity Committee of the Immune Tolerance Network; [4] Naomi M. Kanof Award for Distinguished Achievement in Clinical Investigation, Society for Investigative Dermatology; [5] Washington University Medical School Alumni Achievement Award; [6] Clinical Immunology Society President’s Award; [7] American College of Rheumatology Master; Federation of Clinical Immunology Society Founder’s Award. [8]
Fathman is a member of many professional organizations, including the American Association of Immunologists (AAI) and the Association of American Physicians (AAP), and is past council member of the American Society for Clinical Investigation (ASCI) and past president of the Clinical Immunology Society (CIS). He was associate editor of the Annual Review of Immunology for 25 years and serves on the editorial boards of numerous scientific journals. Fathman has chaired a variety of national and international professional meetings, served on NIH study sections and numerous blue ribbon panels and has written more than 300 articles on his research in molecular and cellular immunology. [4]
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.
Immunology is a branch of biology and medicine that covers the study of immune systems in all organisms.
In immunology, autoimmunity is the system of immune responses of an organism against its own healthy cells, tissues and other normal body constituents. Any disease resulting from this type of immune response is termed an "autoimmune disease". Prominent examples include celiac disease, diabetes mellitus type 1, Henoch–Schönlein purpura, systemic lupus erythematosus, Sjögren syndrome, eosinophilic granulomatosis with polyangiitis, Hashimoto's thyroiditis, Graves' disease, idiopathic thrombocytopenic purpura, Addison's disease, rheumatoid arthritis, ankylosing spondylitis, polymyositis, dermatomyositis, and multiple sclerosis. Autoimmune diseases are very often treated with steroids.
A cytotoxic T cell (also known as TC, cytotoxic T lymphocyte, CTL, T-killer cell, cytolytic T cell, CD8+ T-cell or killer T cell) is a T lymphocyte (a type of white blood cell) that kills cancer cells, cells that are infected by intracellular pathogens (such as viruses or bacteria), or cells that are damaged in other ways.
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.
Anergy, within the realm of immunology, characterizes the absence of a response from the body's defense mechanisms when confronted with foreign substances. This phenomenon involves the direct induction of peripheral lymphocyte tolerance. When an individual is in a state of anergy, it signifies that their immune system is incapable of mounting a typical response against a specific antigen, typically a self-antigen. The term anergy specifically refers to lymphocytes that exhibit an inability to react to their designated antigen. Notably, anergy constitutes one of the essential processes fostering tolerance within the immune system, alongside clonal deletion and immunoregulation. These processes collectively act to modify the immune response, preventing the inadvertent self-destruction that could result from an overactive immune system.
The National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) is one of the institutes and centers that make up the National Institutes of Health, an agency of the United States Department of Health and Human Services (HHS).
Superantigens (SAgs) are a class of antigens that result in excessive activation of the immune system. Specifically they cause non-specific activation of T-cells resulting in polyclonal T cell activation and massive cytokine release. Superantigens act by binding to the MHC proteins on antigen-presenting cells (APCs) and to the TCRs on their adjacent helper T-cells, bringing the signaling molecules together, and thus leading to the activation of the T-cells, regardless of the peptide displayed on the MHC molecule. SAgs are produced by some pathogenic viruses and bacteria most likely as a defense mechanism against the immune system. Compared to a normal antigen-induced T-cell response where 0.0001-0.001% of the body's T-cells are activated, these SAgs are capable of activating up to 20% of the body's T-cells. Furthermore, Anti-CD3 and Anti-CD28 antibodies (CD28-SuperMAB) have also shown to be highly potent superantigens.
X-linked severe combined immunodeficiency (X-SCID) is an immunodeficiency disorder in which the body produces very few T cells and NK cells.
CD154, also called CD40 ligand or CD40L, is a protein that is primarily expressed on activated T cells and is a member of the TNF superfamily of molecules. It binds to CD40 on antigen-presenting cells (APC), which leads to many effects depending on the target cell type. In total CD40L has three binding partners: CD40, α5β1 integrin and integrin αIIbβ3. CD154 acts as a costimulatory molecule and is particularly important on a subset of T cells called T follicular helper cells. On TFH cells, CD154 promotes B cell maturation and function by engaging CD40 on the B cell surface and therefore facilitating cell-cell communication. A defect in this gene results in an inability to undergo immunoglobulin class switching and is associated with hyper IgM syndrome. Absence of CD154 also stops the formation of germinal centers and therefore prohibiting antibody affinity maturation, an important process in the adaptive immune system.
Certain sites of the mammalian body have immune privilege, meaning they are able to tolerate the introduction of antigens without eliciting an inflammatory immune response. Tissue grafts are normally recognised as foreign antigens by the body and attacked by the immune system. However, in immune privileged sites, tissue grafts can survive for extended periods of time without rejection occurring. Immunologically privileged sites include:
Harald von Boehmer was a German-Swiss immunologist best known for his work on T cells.
An autoimmune disease is a condition that results from an anomalous response of the adaptive immune system, wherein it mistakenly targets and attacks healthy, functioning parts of the body as if they were foreign organisms. It is estimated that there are more than 80 recognized autoimmune diseases, with recent scientific evidence suggesting the existence of potentially more than 100 distinct conditions. Nearly any body part can be involved.
Alan Krensky is executive for development at Northwestern Medicine and vice dean for development and alumni relations at Northwestern's Feinberg School of Medicine. He was previously senior investigator in the Laboratory of Cellular and Molecular Biology at the National Institutes of Health (NIH) and served as the first director of the Office of Portfolio Analysis and Strategic Initiatives (OPASI) and a deputy director of NIH. He was Associate Dean for Children’s Health and the Shelagh Galligan Professor of Pediatrics at Stanford University.
Short Course Immune Induction Therapy or SCIIT, is a therapeutic strategy employing rapid, specific, short term-modulation of the immune system using a therapeutic agent to induce T-cell non-responsiveness, also known as operational tolerance. As an alternative strategy to immunosuppression and antigen-specific tolerance inducing therapies, the primary goal of SCIIT is to re-establish or induce peripheral immune tolerance in the context of autoimmune disease and transplant rejection through the use of biological agents. In recent years, SCIIT has received increasing attention in clinical and research settings as an alternative to immunosuppressive drugs currently used in the clinic, drugs which put the patients at risk of developing infection, cancer, and cardiovascular disease.
Hugh O'Neill McDevitt ForMemRS was an immunologist and Professor of Microbiology and Immunology at Stanford University School of Medicine.
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.
Gene Martin Shearer is an American immunologist who works at the National Institutes of Health (NIH). He first achieved fame for his discovery in 1974 that T lymphocytes recognized chemically modified surface antigens only in the context of self major histocompatibility complex (MHC) encoded molecules, identifying the central feature of antigen recognition by T lymphocytes known as MHC restriction. His discovery of MHC restriction using chemically modified surface antigens was simultaneous with the discovery of MHC restricted T lymphocyte recognition of virus infected cells by Rolf Zinkernagel and Peter Doherty, who received the 1996 Nobel Prize in Physiology or Medicine.
Kendall A. Smith is an American scientist most well-known for his work on interleukins, the regulatory molecules of the immune system, which has led to many of the new present-day therapies for immunological disorders, transplant rejection, infectious diseases and cancer. Smith is a Professor Emeritus of Medicine at Weill Cornell Medicine.
Marc K. Jenkins is a Regents Professor and Director of the Center for Immunology at the University of Minnesota. He is a member of the National Academy of Sciences.
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