Visualizing the Dynamics of Immune Surveillance in Brain Tumors by Intravital Multiphoton Microscopy
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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. -
Innate Immunity in the Lung: How Epithelial Cells Fight Against
Copyright #ERSJournals Ltd 2004 EurRespir J 2004;23: 327– 333 EuropeanRespiratory Journal DOI: 10.1183/09031936.03.00098803 ISSN0903-1936 Printedin UK –allrights reserved REVIEW Innateimmunity in the lung: how epithelialcells ght against respiratorypathogens R. Bals*,P.S. Hiemstra # Innateimmunity in the lung: how epithelial cells ® ghtagainst respiratory pathogens *Deptof Internal Medicine, Division of R Bals, P S Hiemstra #ERS JournalsLtd 2004 PulmonaryMedicine, Hospital of the Uni- versityof Marburg, Philipps-University, ABSTRACT: Thehuman lung is exposed to a largenumber of airborne pathogens as a # resultof the daily inhalation of 10,000 litres of air Theobservation that respiratory Marburg,Germany; Deptof Pulmonology, LeidenUniversity Medical Center, Leiden, infectionsare nevertheless rare is testimony to the presence of anef®cient host defence TheNetherlands systemat the mucosal surface of the lung Theairway epithelium is strategically positioned at the interface with the Correspondence:P S Hiemstra,Dept of environment,and thus plays a keyrole in this host defence system Recognition Pulmonology,Leiden University Medical systemsemployed by airwayepithelial cells to respond to microbialexposure include the Center, P O Box9600, 2300 RC Leiden, The actionof the toll-like receptors Netherlands Theairway epithelium responds to such exposure by increasing its production of Fax:31 715266927 mediatorssuch as cytokines, chemokines and antimicrobial peptides Recent® ndings E-mail: p s hiemstra@lumc nl indicatethe importance of these peptides -
When Two Is Better Than One: Elements of Intravital Microscopy David W
Open access, freely available online Primer When Two Is Better Than One: Elements of Intravital Microscopy David W. Piston ver the last 20 years, many cell biological studies have moved from the single-cell level to the tissue level, Oand even to whole animals. This progress has been led by developments in fl uorescence microscopy that permit molecular observations from single cells within intact tissue or animals. Concurrent developments in fl uorescent probes, especially the cloning of the Green Fluorescent Protein and its use in transgenic animals, have also fueled this movement. The key instrumental technology for this work is optical sectioning microscopy; in this technique, instead of fi xing DOI: 10.1371/journal.pbio.0030207.g001 and physically sectioning a sample, the investigator obtains a 3-D dataset from an intact (and more importantly, live) Figure 1. Images of a Shark Choroid Plexus Stained with Fluorescein specimen. The most common optical sectioning technique (A) and (B) were collected 70 µm into the sample, and (C) is confocal microscopy, where fl uorescence is created was collected 140 µm into the sample. The contrast of the confocal image (A) is signifi cantly degraded at this depth, while throughout the sample and a confocal pinhole is placed in two-photon excitation at the same focal plane (B) allows the front of the detector so that only the in-focus fl uorescence is collection of an image with excellent intensity contrast. Further, recorded. For live samples, whose cells can be killed by the using two-photon excitation to image deeper into the sample (C) excitation light (via photo-toxicity, particularly of ultraviolet does not signifi cantly degrade the image contrast. -
Qnas with Max D. Cooper and Jacques F. A. P. Miller
QNAS QnAswithMaxD.CooperandJacquesF.A.P.Miller QNAS Brian Doctrow, Science Writer Anyone who has ever contracted chicken pox can thank the adaptive immune system for future pro- tection against the disease. It is also thanks to this system that vaccines prevent diseases. The adaptive immune system provides organisms with a memory of past infections, enabling the body to quickly kill returning infections before they can do significant damage. Immunologists Jacques F. A. P. Miller and Max D. Cooper determined that adaptive immunity requires 2 distinct cell types that perform comple- mentary functions. Miller’s findings, published in the early 1960s in Lancet (1) and Proceedings of the Royal Society (2), showed that the ability to distinguish one’s own cells from foreign cells, a key feature of the adap- tive immune system, depends on lymphocytes, now known as T cells, matured in an organ called the thy- mus. Subsequently, Cooper reported in Nature (3) that Max Dale Cooper. Image courtesy of Georgia Research antibody production depends on a separate set of Alliance/Billy Howard. lymphocytes, dubbed B cells. The division of labor between T and B cells is a fundamental organizing principle of the adaptive immune system, the discov- did cancer research. I started working on leukemia and ery of which laid the groundwork for modern immu- this gave me an interest in lymphocytes. nology and made possible many subsequent medical advances, including monoclonal antibody produc- Cooper: I became interested through patients that I tion, vaccine development, and checkpoint inhibi- was taking care of: Children that had deficient immune tion therapies for cancer. -
The Role of Microbiota in the Pathogenesis of Esophageal Adenocarcinoma
biology Review The Role of Microbiota in the Pathogenesis of Esophageal Adenocarcinoma Megan R. Gillespie 1, Vikrant Rai 2 , Swati Agrawal 3 and Kalyana C. Nandipati 3,* 1 School of Medicine, Creighton University, 2500 California Plaza, Omaha, NE 68178, USA; [email protected] 2 Department of Translational Research, College of Osteopathic Medicine of the Pacific, Western University of Health Sciences, Pomona, CA 91766, USA; [email protected] 3 Department of Surgery, Creighton University School of Medicine, 2500 California Plaza, Omaha, NE 68178, USA; [email protected] * Correspondence: [email protected]; Tel.: +1-402-280-5292 Simple Summary: Esophageal adenocarcinoma has a poor 5-year survival rate and is among the highest mortality cancers. Changes in the esophageal microbiome have been associated with cancer pathogenesis; however, the molecular mechanism remains obscure. This review article critically analyzes the molecular mechanisms through which microbiota may mediate the development and progression of esophageal adenocarcinoma and its precursors-gastroesophageal reflux disease and Barrett’s esophagus. It summarizes changes in esophageal microbiome composition in normal and pathologic states and subsequently discusses the role of altered microbiota in disease progression. The potential role of esophageal microbiota in protecting against the development of esophageal adenocarcinoma is also discussed. By doing so, this article highlights specific directions for future research developing microbiome-mediated therapeutics for esophageal adenocarcinoma. Abstract: Esophageal adenocarcinoma (EAC) is associated with poor overall five-year survival. The Citation: Gillespie, M.R.; Rai, V.; incidence of esophageal cancer is on the rise, especially in Western societies, and the pathophysiologic Agrawal, S.; Nandipati, K.C. The Role of Microbiota in the Pathogenesis of mechanisms by which EAC develops are of extreme interest. -
Intravital Microscopy in Tissue Engineering
fbioe-09-627462 February 11, 2021 Time: 18:1 # 1 REVIEW published: 17 February 2021 doi: 10.3389/fbioe.2021.627462 Actually Seeing What Is Going on – Intravital Microscopy in Tissue Engineering Ravikumar Vaghela, Andreas Arkudas, Raymund E. Horch and Maximilian Hessenauer* Department of Plastic and Hand Surgery, University Hospital of Erlangen, Friedrich–Alexander University Erlangen–Nürnberg (FAU), Erlangen, Germany Intravital microscopy (IVM) study approach offers several advantages over in vitro, ex vivo, and 3D models. IVM provides real-time imaging of cellular events, which provides us a comprehensive picture of dynamic processes. Rapid improvement in microscopy techniques has permitted deep tissue imaging at a higher resolution. Advances in fluorescence tagging methods enable tracking of specific cell types. Moreover, IVM can serve as an important tool to study different stages of tissue regeneration processes. Furthermore, the compatibility of different tissue engineered Edited by: Jetze Visser, constructs can be analyzed. IVM is also a promising approach to investigate host Radboud University Medical Center, reactions on implanted biomaterials. IVM can provide instant feedback for improvising Netherlands tissue engineering strategies. In this review, we aim to provide an overview of the Reviewed by: requirements and applications of different IVM approaches. First, we will discuss the Roberto Weigert, National Institute of Dental history of IVM development, and then we will provide an overview of available optical and Craniofacial Research (NIDCR), modalities including the pros and cons. Later, we will summarize different fluorescence United States Lia Rimondini, labeling methods. In the final section, we will discuss well-established chronic and acute University of Eastern Piedmont, Italy IVM models for different organs. -
Human Autoimmunity and Associated Diseases
Human Autoimmunity and Associated Diseases Human Autoimmunity and Associated Diseases Edited by Kenan Demir and Selim Görgün Human Autoimmunity and Associated Diseases Edited by Kenan Demir and Selim Görgün This book first published 2021 Cambridge Scholars Publishing Lady Stephenson Library, Newcastle upon Tyne, NE6 2PA, UK British Library Cataloguing in Publication Data A catalogue record for this book is available from the British Library Copyright © 2021 by Kenan Demir and Selim Görgün and contributors All rights for this book reserved. No part of this book may be reproduced, stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, recording or otherwise, without the prior permission of the copyright owner. ISBN (10): 1-5275-6910-1 ISBN (13): 978-1-5275-6910-2 TABLE OF CONTENTS Preface ...................................................................................................... viii Chapter One ................................................................................................. 1 Introduction to the Immune System Kemal Bilgin Chapter Two .............................................................................................. 10 Immune System Embryology Rümeysa Göç Chapter Three ............................................................................................. 18 Immune System Histology Filiz Yılmaz Chapter Four .............................................................................................. 36 Tolerance Mechanisms and Autoimmunity -
Immunology 101
Immunology 101 Justin Kline, M.D. Assistant Professor of Medicine Section of Hematology/Oncology Committee on Immunology University of Chicago Medicine Disclosures • I served as a consultant on Advisory Boards for Merck and Seattle Genetics. • I will discuss non-FDA-approved therapies for cancer 2 Outline • Innate and adaptive immune systems – brief intro • How immune responses against cancer are generated • Cancer antigens in the era of cancer exome sequencing • Dendritic cells • T cells • Cancer immune evasion • Cancer immunotherapies – brief intro 3 The immune system • Evolved to provide protection against invasive pathogens • Consists of a variety of cells and proteins whose purpose is to generate immune responses against micro-organisms • The immune system is “educated” to attack foreign invaders, but at the same time, leave healthy, self-tissues unharmed • The immune system can sometimes recognize and kill cancer cells • 2 main branches • Innate immune system – Initial responders • Adaptive immune system – Tailored attack 4 The immune system – a division of labor Innate immune system • Initial recognition of non-self (i.e. infection, cancer) • Comprised of cells (granulocytes, monocytes, dendritic cells and NK cells) and proteins (complement) • Recognizes non-self via receptors that “see” microbial structures (cell wall components, DNA, RNA) • Pattern recognition receptors (PRRs) • Necessary for priming adaptive immune responses 5 The immune system – a division of labor Adaptive immune system • Provides nearly unlimited diversity of receptors to protect the host from infection • B cells and T cells • Have unique receptors generated during development • B cells produce antibodies which help fight infection • T cells patrol for infected or cancerous cells • Recognize “foreign” or abnormal proteins on the cell surface • 100,000,000 unique T cells are present in all of us • Retains “memory” against infections and in some cases, cancer. -
Mind, Brain, Immunity
Mind, Brain, Immunity st Ann Fink, Ph.D. Bioscience in the 21 Fri 12/07/2018 Century Today’s Plan 1. Immunity: a review 2. Central nervous system (CNS) structure 3. Cellular, molecular and structural features of CNS and Immune function 4. The lymphatic system and beyond 5. Health relevance of mind-brain-immunity connections 2 What happens when foreign tissue is grafted into the body? Into a leg? Into the brain? Into the leg and then into the brain? Is the brain immune privileged? 3 Innate and adaptive immunity Less specific but faster: mediates More specific immunity: “learns” inflammation, can be “called” by about pathogens (bacteria, adaptive immune system. viruses, etc.) through antibodies. 4 Lymph nodes: an structural network mediating immunity and fluid / molecular exchange in tissues 5 The central, peripheral, and autonomic nervous system 6 https://www.ncbi.nlm.nih.gov/pubmedhealth/PMHT0024762/ Meninges cover the central nervous system 3 Layers: 1. Dura mater (outer) 2. Arachnoid: (middle) 3. Pia mater (inner) Saboori & Sadegh (2015). Anatomy research international, 2015, 279814. 7 And cerebrospinal fluid bathes the brain. By © Nevit Dilmen, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=93 Jessen et al. Neurochem Res. 2015, 40(12): 2583–2599. 88427 8 The blood-brain barrier Astrocytes form a gateway between the bloodstream and the brain. Jessen et al. Neurochem Res. 2015, 40(12): 2583–2599. 9 Based on this information, how could the immune system and central nervous system interact? Your answers here: 10 Immune – CNS interactions Areas of overlap? By Volker Brinkmann - (November 2005). -
Chronic Two-Photon Imaging of Neuronal Activity in Alzheimer's
Zurich Open Repository and Archive University of Zurich Main Library Strickhofstrasse 39 CH-8057 Zurich www.zora.uzh.ch Year: 2012 Chronic two-photon imaging of neuronal activity in alzheimer’s disease animal models Bhat, Annapoorna Posted at the Zurich Open Repository and Archive, University of Zurich ZORA URL: https://doi.org/10.5167/uzh-72425 Dissertation Published Version Originally published at: Bhat, Annapoorna. Chronic two-photon imaging of neuronal activity in alzheimer’s disease animal mod- els. 2012, University of Zurich, Faculty of Science. Chronic Two-photon Imaging of Neuronal Activity in Alzheimer’s Disease Animal Models Dissertation zur Erlangung der naturwissenschaftlichen Doktorwürde (Dr. sc. nat.) vorgelegt der Mathematisch-naturwissenschaftlichen Fakultät der Universität Zürich von Annapoorna Bhat aus Indien Promotionskomitee Prof. Dr. Roger M. Nitsch (Vorsitz, Leitung der Dissertation) Prof. Dr. Fritjof Helmchen (Leitung der Dissertation) Prof. Dr. Markus Rudin Prof. Dr. Esther Stöckli Zürich, 2012 1 2 “It is good to have an end to journey toward; but it is the journey that matters, in the end.” ― Ernest Hemingway 3 4 Table of Contents 1. Abbreviations ...........................................................................................................7 2. Summary/Zusammenfassung ...............................................................................11 3. Introduction............................................................................................................15 3.1 Alzheimer’s Disease .....................................................................................................17 -
Intravital Microscopy of Capillary Hemodynamics in Sickle Cell Disease
Intravital microscopy of capillary hemodynamics in sickle cell disease. H H Lipowsky, … , N U Sheikh, D M Katz J Clin Invest. 1987;80(1):117-127. https://doi.org/10.1172/JCI113036. Research Article Direct intravital microscopic examinations were made in nailfold capillaries in subjects with homozygous sickle cell disease (HbSS red cells). In the resting state, capillary red cell (rbc) flux exhibited greater intermittence compared with normal subjects, which increased with painful crisis. In crisis-free HbSS subjects, capillary occlusion and red cell sequestration occurred in only 8.2% of all capillaries and diminished to 5.8% during crisis, possibly due to sequestration of less deformable rbcs in other organs. Velocities of rbc's (Vrbc) were measured by video techniques under resting conditions and during postocclusive reactive hyperemia (PORH) induced by a pressure cuff around the finger. Resting Vrbc was normal in crisis-free HbSS subjects, averaging 0.7 mm/s. In contrast, Vrbc was significantly elevated during crisis, to 0.98 mm/s, apparently due to compensatory arteriolar dilation. Crisis subjects exhibited a significantly depressed PORH with the ratio of peak red cell velocity to resting values reduced by 15% due to a loss of vasodilatory reserve, whereas crisis-free subjects exhibited a normal response. A 55% increase in the time to attain peak Vrbc was attributed to resistance increases, possibly resulting from red cell and leukocyte-to-endothelium adhesion during the induced ischemia. Find the latest version: https://jci.me/113036/pdf Intravital Microscopy of Capillary Hemodynamics in Sickle Cell Disease Herbert H. Lipowsky, Naeem U. Sheikh, and Donald M. -
Research Techniques Made Simple: Two-Photon Intravital Imaging of the Skin Peyman Obeidy1, Philip L
RESEARCH TECHNIQUES MADE SIMPLE Research Techniques Made Simple: Two-Photon Intravital Imaging of the Skin Peyman Obeidy1, Philip L. Tong1,2,3 and Wolfgang Weninger1,2,3 Over the last few years, intravital two-photon microscopy has matured into a powerful technology helping basic and clinical researchers obtain quantifiable details of complex biological mechanisms in live and intact tissues. Two-photon microscopy provides high spatial and temporal resolution in vivo with little phototoxicity that is unattainable by other optical tools like confocal microscopy. Using ultrashort laser pulses, two-photon microscopy allows the visualization of molecules, cells, and extracellular structures up to depths of 1 mm within tissues. Consequently, real-time imaging of the individual skin layers under both physiological and pathological conditions has revolutionized our understanding of cutaneous homeostasis, immunity, and tumor biology. This review provides an overview to two-photon microscopy of the skin by covering the basic concepts and current applications in diverse preclinical and clinical settings. Journal of Investigative Dermatology (2018) 138, 720e725; doi:10.1016/j.jid.2018.01.017 CME Activity Dates: 21 March 2018 CME Accreditation and Credit Designation: This activity has Expiration Date: 20 March 2019 been planned and implemented in accordance with the Estimated Time to Complete: 1 hour accreditation requirements and policies of the Accreditation Council for Continuing Medical Education through the joint Planning Committee/Speaker Disclosure: All authors, providership of Beaumont Health and the Society for Inves- planning committee members, CME committee members tigative Dermatology. Beaumont Health is accredited by the and staff involved with this activity as content validation fi ACCME to provide continuing medical education for physi- reviewers have no nancial relationship(s) with commercial cians.