The Immune System
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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. -
Our Immune System (Children's Book)
OurOur ImmuneImmune SystemSystem A story for children with primary immunodeficiency diseases Written by IMMUNE DEFICIENCY Sara LeBien FOUNDATION A note from the author The purpose of this book is to help young children who are immune deficient to better understand their immune system. What is a “B-cell,” a “T-cell,” an “immunoglobulin” or “IgG”? They hear doctors use these words, but what do they mean? With cheerful illustrations, Our Immune System explains how a normal immune system works and what treatments may be necessary when the system is deficient. In this second edition, a description of a new treatment has been included. I hope this book will enable these children and their families to explore together the immune system, and that it will help alleviate any confusion or fears they may have. Sara LeBien This book contains general medical information which cannot be applied safely to any individual case. Medical knowledge and practice can change rapidly. Therefore, this book should not be used as a substitute for professional medical advice. SECOND EDITION COPYRIGHT 1990, 2007 IMMUNE DEFICIENCY FOUNDATION Copyright 2007 by Immune Deficiency Foundation, USA. Readers may redistribute this article to other individuals for non-commercial use, provided that the text, html codes, and this notice remain intact and unaltered in any way. Our Immune System may not be resold, reprinted or redistributed for compensation of any kind without prior written permission from Immune Deficiency Foundation. If you have any questions about permission, please contact: Immune Deficiency Foundation, 40 West Chesapeake Avenue, Suite 308, Towson, MD 21204, USA; or by telephone at 1-800-296-4433. -
Assessing the Tumor Microenvironment by Recovery of Immune Receptor V(D)J Recombination Reads from Tumor Specimen Exome Files
Assessing the Tumor Microenvironment by Recovery of Immune Receptor V(D)J Recombination Reads from Tumor Specimen Exome Files George Blanck, Ph.D. Professor, Molecular Medicine Morsani College of Medicine, USF Immunology Program, Moffitt Cancer Center (not for publication or public web page) Learning objectives: 1. To appreciate the availability of T-cell receptor recombination information from tumor specimen DNA samples. 2. To understand the correlation between T-cell receptor recombinations, in tumor specimen DNA, and other, clinically relevant information for bladder cancer and kidney renal cell carcinoma. 3. To understand the importance of HLA alleles in assessing the impact of T-cell receptor recombinations from tumor specimen DNA. Fig. 1. Immune receptor genes recombine during development to generate many different receptor molecules among the B-cells and T- cells, throughout the body, through life, to bind many different antigens, including tumor antigens. Seven immune receptor genes total: • Three related to antibodies, not further discussed. • Two related to gamma-delta T-cells, not further discussed • Two required for alpha-beta T-cells, the subject of this presentation. Alpha-beta T-cells: • Most numerous. • Best understood, medically speaking. • Generally target peptide antigen, in the case of tumors, a mutant peptide. • The TRB part of the TRA/TRB receptor is considered most important in antigen binding. The tumor specimen and the exome • Surgically remove tumor, obtain DNA sequence (all exons = exome), for tumor mutations, which can guide therapy. • Other cells in the specimen, particularly T-cells. • The DNA representing the T-cell receptor can be identified above the tumor DNA “background”. Fig. -
Transcriptional Control of Tissue-Resident Memory T Cell Generation
Transcriptional control of tissue-resident memory T cell generation Filip Cvetkovski Submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy in the Graduate School of Arts and Sciences COLUMBIA UNIVERSITY 2019 © 2019 Filip Cvetkovski All rights reserved ABSTRACT Transcriptional control of tissue-resident memory T cell generation Filip Cvetkovski Tissue-resident memory T cells (TRM) are a non-circulating subset of memory that are maintained at sites of pathogen entry and mediate optimal protection against reinfection. Lung TRM can be generated in response to respiratory infection or vaccination, however, the molecular pathways involved in CD4+TRM establishment have not been defined. Here, we performed transcriptional profiling of influenza-specific lung CD4+TRM following influenza infection to identify pathways implicated in CD4+TRM generation and homeostasis. Lung CD4+TRM displayed a unique transcriptional profile distinct from spleen memory, including up-regulation of a gene network induced by the transcription factor IRF4, a known regulator of effector T cell differentiation. In addition, the gene expression profile of lung CD4+TRM was enriched in gene sets previously described in tissue-resident regulatory T cells. Up-regulation of immunomodulatory molecules such as CTLA-4, PD-1, and ICOS, suggested a potential regulatory role for CD4+TRM in tissues. Using loss-of-function genetic experiments in mice, we demonstrate that IRF4 is required for the generation of lung-localized pathogen-specific effector CD4+T cells during acute influenza infection. Influenza-specific IRF4−/− T cells failed to fully express CD44, and maintained high levels of CD62L compared to wild type, suggesting a defect in complete differentiation into lung-tropic effector T cells. -
Lung Microbiome Participation in Local Immune Response Regulation in Respiratory Diseases
microorganisms Review Lung Microbiome Participation in Local Immune Response Regulation in Respiratory Diseases Juan Alberto Lira-Lucio 1 , Ramcés Falfán-Valencia 1 , Alejandra Ramírez-Venegas 2, Ivette Buendía-Roldán 3 , Jorge Rojas-Serrano 4 , Mayra Mejía 4 and Gloria Pérez-Rubio 1,* 1 HLA Laboratory, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Mexico City 14080, Mexico; [email protected] (J.A.L.-L.); [email protected] (R.F.-V.) 2 Tobacco Smoking and COPD Research Department, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Mexico City 14080, Mexico; [email protected] 3 Translational Research Laboratory on Aging and Pulmonary Fibrosis, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Mexico City 14080, Mexico; [email protected] 4 Interstitial Lung Disease and Rheumatology Unit, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Mexico City 14080, Mexico; [email protected] (J.R.-S.); [email protected] (M.M.) * Correspondence: [email protected]; Tel.: +52-55-5487-1700 (ext. 5152) Received: 11 June 2020; Accepted: 7 July 2020; Published: 16 July 2020 Abstract: The lung microbiome composition has critical implications in the regulation of innate and adaptive immune responses. Next-generation sequencing techniques have revolutionized the understanding of pulmonary physiology and pathology. Currently, it is clear that the lung is not a sterile place; therefore, the investigation of the participation of the pulmonary microbiome in the presentation, severity, and prognosis of multiple pathologies, such as asthma, chronic obstructive pulmonary disease, and interstitial lung diseases, contributes to a better understanding of the pathophysiology. Dysregulation of microbiota components in the microbiome–host interaction is associated with multiple lung pathologies, severity, and prognosis, making microbiome study a useful tool for the identification of potential therapeutic strategies. -
Cells, Tissues and Organs of the Immune System
Immune Cells and Organs Bonnie Hylander, Ph.D. Aug 29, 2014 Dept of Immunology [email protected] Immune system Purpose/function? • First line of defense= epithelial integrity= skin, mucosal surfaces • Defense against pathogens – Inside cells= kill the infected cell (Viruses) – Systemic= kill- Bacteria, Fungi, Parasites • Two phases of response – Handle the acute infection, keep it from spreading – Prevent future infections We didn’t know…. • What triggers innate immunity- • What mediates communication between innate and adaptive immunity- Bruce A. Beutler Jules A. Hoffmann Ralph M. Steinman Jules A. Hoffmann Bruce A. Beutler Ralph M. Steinman 1996 (fruit flies) 1998 (mice) 1973 Discovered receptor proteins that can Discovered dendritic recognize bacteria and other microorganisms cells “the conductors of as they enter the body, and activate the first the immune system”. line of defense in the immune system, known DC’s activate T-cells as innate immunity. The Immune System “Although the lymphoid system consists of various separate tissues and organs, it functions as a single entity. This is mainly because its principal cellular constituents, lymphocytes, are intrinsically mobile and continuously recirculate in large number between the blood and the lymph by way of the secondary lymphoid tissues… where antigens and antigen-presenting cells are selectively localized.” -Masayuki, Nat Rev Immuno. May 2004 Not all who wander are lost….. Tolkien Lord of the Rings …..some are searching Overview of the Immune System Immune System • Cells – Innate response- several cell types – Adaptive (specific) response- lymphocytes • Organs – Primary where lymphocytes develop/mature – Secondary where mature lymphocytes and antigen presenting cells interact to initiate a specific immune response • Circulatory system- blood • Lymphatic system- lymph Cells= Leukocytes= white blood cells Plasma- with anticoagulant Granulocytes Serum- after coagulation 1. -
A New Role for NKG2D Signaling in CD8 T Cells and Autoimmune
A new role for NKG2D signaling in CD8+ T cells and autoimmune diabetes By Andrew P Trembath © 2019 Submitted to the graduate degree program in Microbiology, Molecular Genetics and Immunology, and the Graduate Faculty of the University of Kansas in partial fulfillment of the requirements for the degree of Doctor of Philosophy. Chair: Mary A. Markiewicz Ph.D Wolfram R. Zückert Ph.D. Patrick E. Fields, Ph.D. Maria Kalamvoki Ph.D. Joe Lutkenhaus Ph.D Date Defended: 11/13/2019 ii The dissertation committee for Andrew Trembath certifies that this is the approved version of the following dissertation: A new role for NKG2D signaling in CD8+ T cells and autoimmune diabetes Chair: Mary A. Markiewicz, Ph.D. Date Approved: 12/19/2019 iii Abstract The demands placed on the immune system are immense and highly complex. It must protect the body against untold threats while maintaining a balance between immune defense and autoimmune damage. One major player in immune recognition is the receptor Natural-Killer- Group-2-Member-D (NKG2D), best known for its expression on natural killer (NK) cells and CD8+ T cells, where it recognizes NKG2D ligands expressed by stressed cells following viral infection or cancerous transformation. NKG2D is most well studied for its role in tumor immunity, for which NKG2D based therapies are currently being developed clinically. Despite this, it is apparent that NKG2D has other poorly understood immune regulating functions, such as its implicated involvement in type 1diabetes and other autoimmune disorders. However, the mechanism by which NKG2D signaling affects diabetes has been unclear. We therefore sought to further clarify the role NKG2D plays in autoimmune diabetes development. -
Toll and Toll-Like Receptor Signalling in Development Niki Anthoney*, Istvan Foldi‡ and Alicia Hidalgo§
View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Repository of the Academy's Library © 2018. Published by The Company of Biologists Ltd | Development (2018) 145, dev156018. doi:10.1242/dev.156018 DEVELOPMENT AT A GLANCE Toll and Toll-like receptor signalling in development Niki Anthoney*, Istvan Foldi‡ and Alicia Hidalgo§ ABSTRACT signalling and discuss how this signalling pathway regulates various The membrane receptor Toll and the related Toll-like receptors aspects of development across species. (TLRs) are best known for their universal function in innate immunity. KEY WORDS: Toll, Tol-1, TLR, TIR-NBS-LRR, Sarm, MyD88, NF-κB, However, Toll/TLRs were initially discovered in a developmental Dorsal, Wek, JNK, FoxO, Cell death, Cell survival, Cell fate, context, and recent studies have revealed that Toll/TLRs carry out Cell proliferation, Structural plasticity, Signalling previously unanticipated functions in development, regulating cell fate, cell number, neural circuit connectivity and synaptogenesis. Introduction Furthermore, knowledge of their molecular mechanisms of action is The Drosophila gene Toll is possibly the only gene associated with expanding and has highlighted that Toll/TLRs function beyond the two Nobel Prizes: it was discovered as one of the key genes canonical NF-κB pathway to regulate cell-to-cell communication and determining body plan, and was later rediscovered for its role in signalling at the synapse. Here, we provide an overview of Toll/TLR underlying innate immunity (leading to the 1995 and 2011 Nobel Prizes in Physiology or Medicine, respectively). Searches for Toll NeuroDevelopment Group, School of Biosciences, University of Birmingham, homologues led to the identification of Toll-like receptor (TLR) Birmingham B15 2TT, UK. -
Hormones and the Immune Response
Ann Rheum Dis: first published as 10.1136/ard.48.1.1 on 1 January 1989. Downloaded from Annals of the Rheumatic Diseases, 1989; 48, 1-6 Review Hormones and the immune response Recent advances suggest that the immune system cells, are present on mouse spleen cells3 and human does not function in isolation but is influenced by peripheral blood mononuclear cells.4 Receptors, other physiological systems such as the endocrine identical to those in the central nervous system, for and neuroendocrine systems. This review discusses methionine enkephalin are present on splenocytes aspects of immune function altered by neuroendo- and T lymphocytes.3 In contrast, leucine enkephalin crine peptides, sex hormones, and vitamin D and j3-endorphin receptors on T lymphocyte differ metabolites. from those in the central nervous system as binding cannot be inhibited by opiate antagonists.5 6 In the Neuroendocrine effects case of ,3-endorphin the bindings occur through its carboxy terminal, whereas opiates bind their A system of bidirectional communication between receptor through the amino terminus. This raises the immune and neuroendocrine system exists, in an interesting possibility that a peptide such as which the two systems share a common set of f6-endorphin could form a bridge between two hormones and receptors.'2 Not only do immune lymphocyte subtypes by binding to one through its for peptides, to the and cells possess receptors neuroendocrine amino terminus opiate receptor through copyright. they are also capable of synthesising them and of its carboxy terminus to the non-opiate receptor on responding to them. Products of immune cells affect another lymphocyte.4 the central nervous system, which possesses recep- Other neuroendocrine peptide receptors present tors for cytokines and can also synthesise them on leucocztes include those for neurotensin,7 sub- (Fig. -
Mast Cell Signaling: the Role of Protein Tyrosine Kinase Syk, Its Activation and Screening Methods for New Pathway Participants
View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Elsevier - Publisher Connector FEBS Letters 584 (2010) 4933–4940 journal homepage: www.FEBSLetters.org Review Mast cell signaling: The role of protein tyrosine kinase Syk, its activation and screening methods for new pathway participants Reuben P. Siraganian *, Rodrigo O. de Castro, Emilia A. Barbu, Juan Zhang Receptors and Signal Transduction Section, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bldg. 49, Rm. 1A16, Bethesda, MD 20892, USA article info abstract Article history: The aggregation by antigen of the IgE bound to its high affinity receptor on mast cells initiates a Received 27 July 2010 complex series of biochemical events that result in the release of inflammatory mediators. The Accepted 3 August 2010 essential role of the protein tyrosine kinase Syk has been appreciated for some time, and newer Available online 7 August 2010 results have defined the mechanism of its activation. The use of siRNA has defined the relative con- tribution of Syk, Fyn and Gab2 to signaling and has made possible a screening study to identify pre- Edited by Israel Pecht viously unrecognized molecules that are involved in these pathways. Published by Elsevier B.V. on behalf of the Federation of European Biochemical Societies. Keywords: Mast cell FceRI signal transduction Syk Fyn Gab2 Phosphatase 1. Introduction The a-chain binds the Fc portion of IgE at ratio of 1:1 while the b- and c-chains contain ITAMs in their cytoplasmic domains. Be- The activation of mast cells or basophils initiates a series of bio- cause FceRI has no intrinsic enzymatic activity, the activation of chemical events which result in the release of biologically active non-receptor protein tyrosine kinases are essential for cell activa- mediators that cause allergic reactions. -
Understanding the Immune System: How It Works
Understanding the Immune System How It Works U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES NATIONAL INSTITUTES OF HEALTH National Institute of Allergy and Infectious Diseases National Cancer Institute Understanding the Immune System How It Works U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES NATIONAL INSTITUTES OF HEALTH National Institute of Allergy and Infectious Diseases National Cancer Institute NIH Publication No. 03-5423 September 2003 www.niaid.nih.gov www.nci.nih.gov Contents 1 Introduction 2 Self and Nonself 3 The Structure of the Immune System 7 Immune Cells and Their Products 19 Mounting an Immune Response 24 Immunity: Natural and Acquired 28 Disorders of the Immune System 34 Immunology and Transplants 36 Immunity and Cancer 39 The Immune System and the Nervous System 40 Frontiers in Immunology 45 Summary 47 Glossary Introduction he immune system is a network of Tcells, tissues*, and organs that work together to defend the body against attacks by “foreign” invaders. These are primarily microbes (germs)—tiny, infection-causing Bacteria: organisms such as bacteria, viruses, streptococci parasites, and fungi. Because the human body provides an ideal environment for many microbes, they try to break in. It is the immune system’s job to keep them out or, failing that, to seek out and destroy them. Virus: When the immune system hits the wrong herpes virus target or is crippled, however, it can unleash a torrent of diseases, including allergy, arthritis, or AIDS. The immune system is amazingly complex. It can recognize and remember millions of Parasite: different enemies, and it can produce schistosome secretions and cells to match up with and wipe out each one of them. -
Replication in the Lung and Immune System Alerted
Replication in the lung and immune system alerted The viral load study in Germany showed that active viral replication occurs in the upper respiratory tract. Seven out of nine participants listed a cough among their initial symptoms. In contrast to the falling numbers of viral units in the upper respiratory tract, numbers in sputum rose for most of the participants. In two individuals with some signs of lung infection, the virus in sputum peaked at day 10- 11. It was present in the sputum up to day 28 in one person. Across all participants, there was an average of 7 million units millilitre (about 35 million units a teaspoon), this amount is about 1000 times more than that in people with SARS In the lung, the ACE2 receptor sits on top of lung cells called pneumocystis. These have an important role in producing surfactant- a compound that coats the air sacs (alveoli), thus helping maintain enough surface tension to keep the sacs open for the exchange of oxygen and carbon dioxide. As soon as the body recognizes foreign protein, it mounts the first response. One part of the body’s immune response- The lymphocytes- begin to produce the first defence IgM-type antibodies and then the longer-term specific neutralizing antibodies (the IgG type). In the German viral study, 50% of the participants had IgM or IgG antibodies by day 7, and they all had these antibodies by day 14. The amount of antibodies did not predict the clinical course of the disease. 80% of people with COVID-19 will have mild or asymptomatic disease, with common symptoms including fever, cough, and loss of sense of smell.