Mechanisms of Autoimmunity —Recent Concept—
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IFM Innate Immunity Infographic
UNDERSTANDING INNATE IMMUNITY INTRODUCTION The immune system is comprised of two arms that work together to protect the body – the innate and adaptive immune systems. INNATE ADAPTIVE γδ T Cell Dendritic B Cell Cell Macrophage Antibodies Natural Killer Lymphocites Neutrophil T Cell CD4+ CD8+ T Cell T Cell TIME 6 hours 12 hours 1 week INNATE IMMUNITY ADAPTIVE IMMUNITY Innate immunity is the body’s first The adaptive, or acquired, immune line of immunological response system is activated when the innate and reacts quickly to anything that immune system is not able to fully should not be present. address a threat, but responses are slow, taking up to a week to fully respond. Pathogen evades the innate Dendritic immune system T Cell Cell Through antigen Pathogen presentation, the dendritic cell informs T cells of the pathogen, which informs Macrophage B cells B Cell B cells create antibodies against the pathogen Macrophages engulf and destroy Antibodies label invading pathogens pathogens for destruction Scientists estimate innate immunity comprises approximately: The adaptive immune system develops of the immune memory of pathogen exposures, so that 80% system B and T cells can respond quickly to eliminate repeat invaders. IMMUNE SYSTEM AND DISEASE If the immune system consistently under-responds or over-responds, serious diseases can result. CANCER INFLAMMATION Innate system is TOO ACTIVE Innate system NOT ACTIVE ENOUGH Cancers grow and spread when tumor Certain diseases trigger the innate cells evade detection by the immune immune system to unnecessarily system. The innate immune system is respond and cause excessive inflammation. responsible for detecting cancer cells and This type of chronic inflammation is signaling to the adaptive immune system associated with autoimmune and for the destruction of the cancer cells. -
Primary Sjogren Syndrome: Focus on Innate Immune Cells and Inflammation
Review Primary Sjogren Syndrome: Focus on Innate Immune Cells and Inflammation Chiara Rizzo 1, Giulia Grasso 1, Giulia Maria Destro Castaniti 1, Francesco Ciccia 2 and Giuliana Guggino 1,* 1 Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, Rheumatology Section, University of Palermo, Piazza delle Cliniche 2, 90110 Palermo, Italy; [email protected] (C.R.); [email protected] (G.G.); [email protected] (G.M.D.C.) 2 Department of Precision Medicine, University of Campania “Luigi Vanvitelli”, Via L. De Crecchio 7, 80138 Naples, Italy; [email protected] * Correspondence: [email protected]; Tel.: +39-091-6552260 Received: 30 April 2020; Accepted: 29 May 2020; Published: 3 June 2020 Abstract: Primary Sjogren Syndrome (pSS) is a complex, multifactorial rheumatic disease that mainly targets salivary and lacrimal glands, inducing epithelitis. The cause behind the autoimmunity outbreak in pSS is still elusive; however, it seems related to an aberrant reaction to exogenous triggers such as viruses, combined with individual genetic pre-disposition. For a long time, autoantibodies were considered as the hallmarks of this disease; however, more recently the complex interplay between innate and adaptive immunity as well as the consequent inflammatory process have emerged as the main mechanisms of pSS pathogenesis. The present review will focus on innate cells and on the principal mechanisms of inflammation connected. In the first part, an overview of innate cells involved in pSS pathogenesis is provided, stressing in particular the role of Innate Lymphoid Cells (ILCs). Subsequently we have highlighted the main inflammatory pathways, including intra- and extra-cellular players. -
Vaccination and Autoimmune Disease: What Is the Evidence?
REVIEW Review Vaccination and autoimmune disease: what is the evidence? David C Wraith, Michel Goldman, Paul-Henri Lambert As many as one in 20 people in Europe and North America have some form of autoimmune disease. These diseases arise in genetically predisposed individuals but require an environmental trigger. Of the many potential environmental factors, infections are the most likely cause. Microbial antigens can induce cross-reactive immune responses against self-antigens, whereas infections can non-specifically enhance their presentation to the immune system. The immune system uses fail-safe mechanisms to suppress infection-associated tissue damage and thus limits autoimmune responses. The association between infection and autoimmune disease has, however, stimulated a debate as to whether such diseases might also be triggered by vaccines. Indeed there are numerous claims and counter claims relating to such a risk. Here we review the mechanisms involved in the induction of autoimmunity and assess the implications for vaccination in human beings. Autoimmune diseases affect about 5% of individuals in Autoimmune disease and infection developed countries.1 Although the prevalence of most Human beings have a highly complex immune system autoimmune diseases is quite low, their individual that evolved from the fairly simple system found in incidence has greatly increased over the past few years, as invertebrates. The so-called innate invertebrate immune documented for type 1 diabetes2,3 and multiple sclerosis.4 system responds non-specifically to infection, does not Several autoimmune disorders arise in individuals in age- involve lymphocytes, and hence does not display groups that are often selected as targets for vaccination memory. -
Autoimmunity and Organ Damage in Systemic Lupus Erythematosus
REVIEW ARTICLE https://doi.org/10.1038/s41590-020-0677-6 Autoimmunity and organ damage in systemic lupus erythematosus George C. Tsokos ✉ Impressive progress has been made over the last several years toward understanding how almost every aspect of the immune sys- tem contributes to the expression of systemic autoimmunity. In parallel, studies have shed light on the mechanisms that contribute to organ inflammation and damage. New approaches that address the complicated interaction between genetic variants, epigen- etic processes, sex and the environment promise to enlighten the multitude of pathways that lead to what is clinically defined as systemic lupus erythematosus. It is expected that each patient owns a unique ‘interactome’, which will dictate specific treatment. t took almost 100 years to realize that lupus erythematosus, strongly to the heterogeneity of the disease. Several genes linked to which was initially thought to be a skin entity, is a systemic the immune response are regulated through long-distance chroma- Idisease that spares no organ and that an aberrant autoimmune tin interactions10,11. Studies addressing long-distance interactions response is involved in its pathogenesis. The involvement of vital between gene variants in SLE are still missing, but, with the advent organs and tissues such as the brain, blood and the kidney in most of new technologies, such studies will emerge. patients, the vast majority of whom are women of childbearing age, Better understanding of the epigenome is needed to under- impels efforts to develop diagnostic tools and effective therapeu- stand how it supplements the genetic contribution to the dis- tics. The prevalence ranges from 20 to 150 cases per 100,000 peo- ease. -
"Epitope Mapping: B-Cell Epitopes". In: Encyclopedia of Life Sciences
Epitope Mapping: B-cell Advanced article Epitopes Article Contents . Introduction GE Morris, Wolfson Centre for Inherited Neuromuscular Disease RJAH Orthopaedic Hospital, . What Is a B-cell Epitope? . Epitope Mapping Methods Oswestry, UK and Keele University, Keele, Staffordshire, UK . Applications Immunoglobulin molecules are folded to present a surface structure complementary to doi: 10.1002/9780470015902.a0002624.pub2 a surface feature on the antigen – the epitope is this feature of the antigen. Epitope mapping is the process of locating the antibody-binding site on the antigen, although the term is also applied more broadly to receptor–ligand interactions unrelated to the immune system. Introduction formed of highly convoluted peptide chains, so that resi- dues that lie close together on the protein surface are often Immunoglobulin molecules are folded in a way that as- far apart in the amino acid sequence (Barlow et al., 1986). sembles sequences from the variable regions of both the Consequently, most epitopes on native, globular proteins heavy and light chains into a surface feature (comprised of are conformation-dependent and they disappear if the up to six complementarity-determining regions (CDRs)) protein is denatured or fragmented. Sometimes, by acci- that is complementary in shape to a surface structure on the dent or design, antibodies are produced against linear antigen. These two surface features, the ‘paratope’ on the (sequential) epitopes that survive denaturation, though antibody and the ‘epitope’ on the antigen, may have a cer- such antibodies usually fail to recognize the native protein. tain amount of flexibility to allow an ‘induced fit’ between The simplest way to find out whether an epitope is confor- them. -
Discussion of Natural Killer Cells and Innate Immunity
Discussion of natural killer cells and innate immunity Theresa L. Whiteside, Ph.D. University of Pittsburgh Cancer Institute Pittsburgh, PA 15213 Myths in tumor immunology • Cancer cells are ignored by the immune system • Immune responses are directed only against “unique” antigens expressed on tumor cells • Tumor-specific T cells alone are sufficient for tumor regression • Tumor are passive targets for anti-tumor responses Tumor/Immune Cells Interactions Tumor cell death C G DC M TUMOR NK Th B Tc Ab Ag Ag/Ab complex NK cells as anti-tumor effectors • LGL, no TCR, express FcγRIII, other activating receptors and KIRs • Spare normal cells but kill a broad range of tumor cells ex vivo by at least two different mechanisms • Produce a number of cytokines (IFN-γ, TNF-α) • Constitutively express IL-2Rβγ and rapidly respond to IL-2 and also to IL-15 and IFNα/β • Regulated by a balance of inhibitory receptors specific for MHC class I antigens and activating signals • NK-DC interactions at sites of inflammation Heterogeneity of human NK cells • Every NK cell expresses at least one KIR that recognizes a self MHC class I molecule • Two functionally distinct subsets: 1) 90% CD56dimCD16bright , highly cytotoxic, abundant KIR expression, few cytokines 2) 10% CD56brightCD16dim/neg, produce cytokines, poorly cytotoxic, low KIR expression Expression of activating and inhibitory receptors on NK cells Interaction with CD56 Interaction with MHC ligands non-MHC ligands KIR CD16 CD2 CD94/NKG2A/B β2 NKp46, 44, 30 CD94/NKG2C/E NK Cell 2B4 NKG2D Lair1 LIR/ILT A -
Pathophysiology of Immune Thrombocytopenic Purpura: a Bird's-Eye View
Egypt J Pediatr Allergy Immunol 2014;12(2):49-61. Review article Pathophysiology of immune thrombocytopenic purpura: a bird's-eye view. Amira Abdel Moneam Adly Pediatrics Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt ABSTRACT and B lymphocytes (including T-helper, T- Immune thrombocytopenic purpura (ITP) is a cytotoxic, and T-regulatory lymphocytes) 6. common autoimmune disorder resulting in isolated The triggering event for ITP is unknown7, but thrombocytopenia. It is a bleeding disorder continued research is providing new insights into characterized by low platelet counts due to decreased the underlying immunopathogenic processes as well platelet production as well as increased platelet as the cellular and molecular mechanisms involved destruction by autoimmune mechanisms. ITP can in megakaryocytopoiesis and platelet turnover. present either alone (primary) or in the setting of other Although historically ITP-associated thrombo- conditions (secondary) such as infections or altered cytopenia was attributed solely to increased rates of immune states. ITP is associated with a loss of destruction of antibody- coated platelets, it has tolerance to platelet antigens and a phenotype of become evident that suboptimal platelet production accelerated platelet destruction and impaired platelet also plays a role 8. production. Although the etiology of ITP remains Bleeding is due to decreased platelet production unknown, complex dysregulation of the immune as well as accelerated platelet destruction mediated system is observed in ITP patients. Antiplatelet in part by autoantibody-based destruction antibodies mediate accelerated clearance from the mechanisms9. Most autoantibodies in ITP are circulation in large part via the reticuloendothelial isotype switched and harbor somatic mutations10, (monocytic phagocytic) system. -
Adoptive Cell Therapy Using Engineered Natural Killer Cells
Bone Marrow Transplantation (2019) 54:785–788 https://doi.org/10.1038/s41409-019-0601-6 REVIEW ARTICLE Adoptive cell therapy using engineered natural killer cells Katayoun Rezvani1 © The Author(s), under exclusive licence to Springer Nature Limited 2019 Abstract The generation of autologous T cells expressing a chimeric antigen receptor (CAR) have revolutionized the field of adoptive cellular therapy. CAR-T cells directed against CD19 have resulted in remarkable clinical responses in patients affected by B-lymphoid malignancies. However, the production of allogeneic CAR-T cells products remains expensive and clinically challenging. Moreover, the toxicity profile of CAR T-cells means that currently these life-saving treatments are only delivered in specialized centers. Therefore, efforts are underway to develop reliable off-the-shelf cellular products with acceptable safety profiles for the treatment of patients with cancer. Natural killer (NK) cells are innate effector lymphocytes with potent antitumor activity. The availability of NK cells from multiple sources and their proven safety profile in the allogeneic setting positions them as attractive contenders for cancer immunotherapy. In this review, we discuss advantages and potential drawbacks of using NK cells as a novel cellular therapy against hematologic malignancies, as well as strategies 1234567890();,: 1234567890();,: to further enhance their effector function. Introduction need for inpatient care may ultimately be economically unviable for many health care systems; (iii) the longer time Adoptive cell therapy has become a powerful treatment that is required to generate CAR T-cells may result in modality for advanced cancers refractory to conventional unavoidable delays in therapy, especially for patients with therapy. -
B Cell Activation and Escape of Tolerance Checkpoints: Recent Insights from Studying Autoreactive B Cells
cells Review B Cell Activation and Escape of Tolerance Checkpoints: Recent Insights from Studying Autoreactive B Cells Carlo G. Bonasia 1 , Wayel H. Abdulahad 1,2 , Abraham Rutgers 1, Peter Heeringa 2 and Nicolaas A. Bos 1,* 1 Department of Rheumatology and Clinical Immunology, University Medical Center Groningen, University of Groningen, 9713 Groningen, GZ, The Netherlands; [email protected] (C.G.B.); [email protected] (W.H.A.); [email protected] (A.R.) 2 Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, 9713 Groningen, GZ, The Netherlands; [email protected] * Correspondence: [email protected] Abstract: Autoreactive B cells are key drivers of pathogenic processes in autoimmune diseases by the production of autoantibodies, secretion of cytokines, and presentation of autoantigens to T cells. However, the mechanisms that underlie the development of autoreactive B cells are not well understood. Here, we review recent studies leveraging novel techniques to identify and characterize (auto)antigen-specific B cells. The insights gained from such studies pertaining to the mechanisms involved in the escape of tolerance checkpoints and the activation of autoreactive B cells are discussed. Citation: Bonasia, C.G.; Abdulahad, W.H.; Rutgers, A.; Heeringa, P.; Bos, In addition, we briefly highlight potential therapeutic strategies to target and eliminate autoreactive N.A. B Cell Activation and Escape of B cells in autoimmune diseases. Tolerance Checkpoints: Recent Insights from Studying Autoreactive Keywords: autoimmune diseases; B cells; autoreactive B cells; tolerance B Cells. Cells 2021, 10, 1190. https:// doi.org/10.3390/cells10051190 Academic Editor: Juan Pablo de 1. -
COVID-19 Natural Immunity
COVID-19 natural immunity Scientific brief 10 May 2021 Key Messages: • Within 4 weeks following infection, 90-99% of individuals infected with the SARS-CoV-2 virus develop detectable neutralizing antibodies. • The strength and duration of the immune responses to SARS-CoV-2 are not completely understood and currently available data suggests that it varies by age and the severity of symptoms. Available scientific data suggests that in most people immune responses remain robust and protective against reinfection for at least 6-8 months after infection (the longest follow up with strong scientific evidence is currently approximately 8 months). • Some variant SARS-CoV-2 viruses with key changes in the spike protein have a reduced susceptibility to neutralization by antibodies in the blood. While neutralizing antibodies mainly target the spike protein, cellular immunity elicited by natural infection also target other viral proteins, which tend to be more conserved across variants than the spike protein. The ability of emerging virus variants (variants of interest and variants of concern) to evade immune responses is under investigation by researchers around the world. • There are many available serologic assays that measure the antibody response to SARS-CoV-2 infection, but at the present time, the correlates of protection are not well understood. Objective of the scientific brief This scientific brief replaces the WHO Scientific Brief entitled “’Immunity passports’ in the context of COVID-19”, published 24 April 2020.1 This update is focused on what is currently understood about SARS-CoV-2 immunity from natural infection. More information about considerations on vaccine certificates or “passports”will be covered in an update of WHO interim guidance, as requested by the COVID-19 emergency committee.2 Methods A rapid review on the subject was undertaken and scientific journals were regularly screened for articles on COVID-19 immunity to ensure to include all large and robust studies available in the literature at the time of writing. -
Epstein-Barr Virus Epitope-Major Histocompatibility Complex
University of Massachusetts Medical School eScholarship@UMMS Open Access Articles Open Access Publications by UMMS Authors 2020-03-17 Epstein-Barr Virus Epitope-Major Histocompatibility Complex Interaction Combined with Convergent Recombination Drives Selection of Diverse T Cell Receptor alpha and beta Repertoires Anna Gil University of Massachusetts Medical School Et al. Let us know how access to this document benefits ou.y Follow this and additional works at: https://escholarship.umassmed.edu/oapubs Part of the Hemic and Lymphatic Diseases Commons, Immune System Diseases Commons, Immunology and Infectious Disease Commons, Infectious Disease Commons, Microbiology Commons, Virus Diseases Commons, and the Viruses Commons Repository Citation Gil A, Kamga L, Chirravuri-Venkata R, Aslan N, Clark FG, Ghersi D, Luzuriaga K, Selin LK. (2020). Epstein- Barr Virus Epitope-Major Histocompatibility Complex Interaction Combined with Convergent Recombination Drives Selection of Diverse T Cell Receptor alpha and beta Repertoires. Open Access Articles. https://doi.org/10.1128/mBio.00250-20. Retrieved from https://escholarship.umassmed.edu/ oapubs/4191 Creative Commons License This work is licensed under a Creative Commons Attribution 4.0 License. This material is brought to you by eScholarship@UMMS. It has been accepted for inclusion in Open Access Articles by an authorized administrator of eScholarship@UMMS. For more information, please contact [email protected]. RESEARCH ARTICLE Host-Microbe Biology crossm Epstein-Barr Virus Epitope–Major Histocompatibility Complex Interaction Combined with Convergent Recombination Drives Downloaded from Selection of Diverse T Cell Receptor ␣ and  Repertoires Anna Gil,a Larisa Kamga,b Ramakanth Chirravuri-Venkata,c Nuray Aslan,a Fransenio Clark,a Dario Ghersi,c Katherine Luzuriaga,b Liisa K. -
Epitope Spreading: Lessons from Autoimmune Skin Diseases
View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Elsevier - Publisher Connector REVIEW Epitope Spreading: Lessons From Autoimmune Skin Diseases Lawrence S. Chan,*† Carol J. Vanderlugt,‡ Takashi Hashimoto,§ Takeji Nishikawa,¶ John J. Zone,** Martin M. Black,†† Fenella Wojnarowska,‡‡ Seth R. Stevens,§§ Mei Chen,† Janet A. Fairley,¶¶ David T. Woodley,*† Stephen D. Miller,‡ and Kenneth B. Gordon†‡ *Medicine Service, Section of Dermatology, Lakeside Division, VA Chicago Health Care System, Chicago, Illinois, U.S.A.; Departments of †Dermatology and ‡Microbiology and Immunology, Northwestern University Medical School, Chicago, Illinois, U.S.A.; ¶¶Department of Dermatology, Kurume University School of Medicine, Kurume, Japan; ¶Department of Dermatology, Keio University School of Medicine, Tokyo, Japan; **Medicine Service, Section of Dermatology, Salt Lake City VA Medical Center, Salt Lake City, Utah, U.S.A.; ††Department of Dermatopathology, Guy’s and St. Thomas Medical and Dental School, London, U.K.; ‡‡Department of Dermatology, The Oxford Radcliffe Hospital, Oxford, U.K.; §§Department of Dermatology, Case Western Reserve University School of Medicine, Cleveland, Ohio, U.S.A.; ¶¶Department of Dermatology, Medical College of Wisconsin, Milwaukee, Wisconsin, U.S.A. Autoimmune diseases are initiated when patients develop In experimental autoimmune animal diseases, ‘‘epitope aberrant T and/or B cell responses against self proteins. spreading’’ seems to have significant physiologic impor- These responses