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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. -
Defining Natural Antibodies
PERSPECTIVE published: 26 July 2017 doi: 10.3389/fimmu.2017.00872 Defining Natural Antibodies Nichol E. Holodick1*, Nely Rodríguez-Zhurbenko2 and Ana María Hernández2* 1 Department of Biomedical Sciences, Center for Immunobiology, Western Michigan University Homer Stryker M.D. School of Medicine, Kalamazoo, MI, United States, 2 Natural Antibodies Group, Tumor Immunology Division, Center of Molecular Immunology, Havana, Cuba The traditional definition of natural antibodies (NAbs) states that these antibodies are present prior to the body encountering cognate antigen, providing a first line of defense against infection thereby, allowing time for a specific antibody response to be mounted. The literature has a seemingly common definition of NAbs; however, as our knowledge of antibodies and B cells is refined, re-evaluation of the common definition of NAbs may be required. Defining NAbs becomes important as the function of NAb production is used to define B cell subsets (1) and as these important molecules are shown to play numerous roles in the immune system (Figure 1). Herein, we aim to briefly summarize our current knowledge of NAbs in the context of initiating a discussion within the field of how such an important and multifaceted group of molecules should be defined. Edited by: Keywords: natural antibody, antibodies, natural antibody repertoire, B-1 cells, B cell subsets, B cells Harry W. Schroeder, University of Alabama at Birmingham, United States NATURAL ANTIBODY (NAb) PRODUCING CELLS Reviewed by: Andre M. Vale, Both murine and human NAbs have been discussed in detail since the late 1960s (2, 3); however, Federal University of Rio cells producing NAbs were not identified until 1983 in the murine system (4, 5). -
Med-Pathway Zoom Workshop
MCAT Immunology Dr. Phillip Carpenter medpathwaymcat Med-pathway AAMC MCAT Content Outline: Immunology Category 1A: Structure/Function of Proteins/AA Immune System Category 3B: Organ Systems Innate vs. Adaptive Immunity T and B Lymphocytes Macrophages & Phagocytes Tissue-Bone marrow, Spleen, Thymus, Lymph nodes Antigen and Antibody Antigen Presentation Clonal Selection Antigen-Antibody recognition Structure of antibody molecule Self vs. Non-self, Autoimmune Diseases Major Histocompatibility Complex Lab Techniques: ELISA & Western Blotting Hematopoiesis Creates Immune Cells Self vs. Non-self Innate vs Adaptive Innate Immunity Physical Barriers: Skin, mucous membranes, pH Inflammatory mediators: Complement, Cytokines, Prostaglandins Cellular Components: Phagocytes-Neutrophils, Eosinophils, Basophils, Mast Cells Antigen Presenting Cells-Monocytes, Macrophages, Dendritic Cells Adaptive (Acquired) Immunity Composed of B and T lymphocytes: Activated by Innate Immunity B cells: Express B cell receptor and secrete antibodies as plasma cells T cells: Mature in thymus, express TCR surface receptor; Activated by Antigen Presenting Cells (APCs) Direct Immune response (The Ringleaders of immune system) Major Lymphoid Organs TYPE SITE FUNCTION Fetal production of Liver 1° lymphoid cells Hematopoietic production of 1° Bone marrow myeloid and lymphoid cells Receives bone marrow T 1° Thymus cells; site where self is selected from non-self Lymph nodes 2° Sites of antigen activation Spleen of lymphocytes; clearance Macrophages (Sentinel Cells) Pattern Recognition -
B-Cell Lymphomas Differ in Their Responsiveness to Cpg Oligodeoxynucleotides
1490 Vol. 11, 1490–1499, February 15, 2005 Clinical Cancer Research B-Cell Lymphomas Differ in their Responsiveness to CpG Oligodeoxynucleotides Bernd Jahrsdorfer,5 Lars Mu¨hlenhoff,1 responsiveness to CpG oligodeoxynucleotides. Focusing Sue E. Blackwell,5 Moritz Wagner,1 clinical studies on patients with highly CpG oligodeoxynu- cleotide–sensitive B-cell malignancies may improve the Hendrik Poeck,1 Evelyn Hartmann,3 Ralf Jox,1 clinical outcome of such trials. Thomas Giese,4 Bertold Emmerich,2 Stefan Endres,1 5 1 George J. Weiner, and Gunther Hartmann INTRODUCTION 1 2 Division of Clinical Pharmacology and Department of Internal The vast majority of lymphoid neoplasms worldwide are Medicine, Division of Hematology, and 3Department of Otorhinolaryngology, University of Munich, Munich, Germany; derived from B lymphocytes at various stages of differentiation. 4Institute of Immunology, University of Heidelberg, Heidelberg, Neoplasms originating from precursor B cells are rare. Neo- Germany; and 5Holden Comprehensive Cancer Center and plasms derived from mature naive B cells include B-cell chronic Department of Internal Medicine, University of Iowa, Iowa City, Iowa lymphocytic leukemia (B-CLL), B-cell small lymphocytic lymphoma (SLL), and mantle cell lymphoma (MCL). Follicular lymphoma (FL) and diffuse large B-cell lymphoma (LCL) are ABSTRACT derived from germinal center B cells. Memory B cells can Human B cells detect CpG motifs within microbial DNA develop into marginal zone B-cell lymphoma (MZL) and B- via TLR9. Synthetic CpG oligodeoxynucleotides are currently CLL. Plasmacytoma is related to plasma cells (1). The most being tested in clinical trials for the therapy of different types typical lymphomas are of diffuse large B-cell type (33%) of B cell non-Hodgkin’s lymphoma. -
Plasma Cells: Finding New Light at the End of B Cell Development Kathryn L
© 2001 Nature Publishing Group http://immunol.nature.com REVIEW Plasma cells: finding new light at the end of B cell development Kathryn L. Calame Plasma cells are cellular factories devoted entire- Upon plasma cell differentiation, there is a marked increase in ly to the manufacture and export of a single prod- steady-state amounts of Ig heavy and light chain mRNA and, when 2 uct: soluble immunoglobulin (Ig). As the final required for IgM and IgA secretion, J chain mRNA . Whether the increase in Ig mRNA is due to increased transcription, increased mediators of a humoral response, plasma cells mRNA stability or, as seems likely, both mechanisms, remains con- play a critical role in adaptive immunity.Although troversial2. There is also an increase in secreted versus membrane intense effort has been devoted to studying the forms of heavy chain mRNA, as determined by differential use of poly(A) sites that may involve the availability of one component of regulation and requirements for early B cell the polyadenylation machinery, cleavage-stimulation factor Cst-643. development, little information has been avail- To accommodate translation and secretion of the abundant Ig able on plasma cells. However, more recent mRNAs, plasma cells have an increased cytoplasmic to nuclear ratio work—including studies on genetically altered and prominent amounts of rough endoplasmic reticulum and secreto- ry vacuoles. mice and data from microarray analyses—has Numerous B cell–specific surface proteins are down-regulated begun to identify the regulatory cascades that upon plasma cell differentiation, including major histocompatibility initiate and maintain the plasma cell phenotype. complex (MHC) class II, B220, CD19, CD21 and CD22. -
How Are White Blood Cells Classified?
How are white blood cells classified? Copyright 2017 by the Rector and Visitors of the University of Virginia How are white blood cells classified? Types of White Blood Cells: Neutrophil Eosinophil Basophil Lymphocyte Monocyte . The types of white blood cells are shown above. The next page will describe lymphocytes in further detail. A healthy individual has all of these white blood cells types, but within specific ranges. Deviation from these ranges can indicate acute illness or a chronic disease. A mnemonic that is often used to remember the relative amount of each white blood cell that should be present is “Never Let Monkeys Eat Bananas.” Never Neutrophil Highest amounts Let Lymphocyte Monkeys Monocyte Eat Eosinophil Bananas Basophil Lowest amounts . In other words, neutrophils should always be present in higher amounts compared to the other cell types. This will be described further in “A first step in diagnosing LGL leukemia: The blood smear.” Copyright 2017 by the Rector and Visitors of the University of Virginia How are white blood cells classified? Introduction: White blood cells are blood cells that fight infection and disease. Lymphocytes are a type of white blood cell. They can identify antigens (substances foreign to the body) and cause an immune response. There are three types of lymphocytes: T-cell, NK-cell, and B-cell. In healthy adults, 10-15% of the lymphocytes are large granular lymphocytes (LGLs). To learn more about LGL cells, see “A first step in diagnosing LGL leukemia: The blood smear.” A person is diagnosed with LGL leukemia if there is a clonal (copied) population of T-cells or NK-cells present. -
Vaccine Immunology Claire-Anne Siegrist
2 Vaccine Immunology Claire-Anne Siegrist To generate vaccine-mediated protection is a complex chal- non–antigen-specifc responses possibly leading to allergy, lenge. Currently available vaccines have largely been devel- autoimmunity, or even premature death—are being raised. oped empirically, with little or no understanding of how they Certain “off-targets effects” of vaccines have also been recog- activate the immune system. Their early protective effcacy is nized and call for studies to quantify their impact and identify primarily conferred by the induction of antigen-specifc anti- the mechanisms at play. The objective of this chapter is to bodies (Box 2.1). However, there is more to antibody- extract from the complex and rapidly evolving feld of immu- mediated protection than the peak of vaccine-induced nology the main concepts that are useful to better address antibody titers. The quality of such antibodies (e.g., their these important questions. avidity, specifcity, or neutralizing capacity) has been identi- fed as a determining factor in effcacy. Long-term protection HOW DO VACCINES MEDIATE PROTECTION? requires the persistence of vaccine antibodies above protective thresholds and/or the maintenance of immune memory cells Vaccines protect by inducing effector mechanisms (cells or capable of rapid and effective reactivation with subsequent molecules) capable of rapidly controlling replicating patho- microbial exposure. The determinants of immune memory gens or inactivating their toxic components. Vaccine-induced induction, as well as the relative contribution of persisting immune effectors (Table 2.1) are essentially antibodies— antibodies and of immune memory to protection against spe- produced by B lymphocytes—capable of binding specifcally cifc diseases, are essential parameters of long-term vaccine to a toxin or a pathogen.2 Other potential effectors are cyto- effcacy. -
B-Cell Development, Activation, and Differentiation
B-Cell Development, Activation, and Differentiation Sarah Holstein, MD, PhD Nov 13, 2014 Lymphoid tissues • Primary – Bone marrow – Thymus • Secondary – Lymph nodes – Spleen – Tonsils – Lymphoid tissue within GI and respiratory tracts Overview of B cell development • B cells are generated in the bone marrow • Takes 1-2 weeks to develop from hematopoietic stem cells to mature B cells • Sequence of expression of cell surface receptor and adhesion molecules which allows for differentiation of B cells, proliferation at various stages, and movement within the bone marrow microenvironment • Immature B cell leaves the bone marrow and undergoes further differentiation • Immune system must create a repertoire of receptors capable of recognizing a large array of antigens while at the same time eliminating self-reactive B cells Overview of B cell development • Early B cell development constitutes the steps that lead to B cell commitment and expression of surface immunoglobulin, production of mature B cells • Mature B cells leave the bone marrow and migrate to secondary lymphoid tissues • B cells then interact with exogenous antigen and/or T helper cells = antigen- dependent phase Overview of B cells Hematopoiesis • Hematopoietic stem cells (HSCs) source of all blood cells • Blood-forming cells first found in the yolk sac (primarily primitive rbc production) • HSCs arise in distal aorta ~3-4 weeks • HSCs migrate to the liver (primary site of hematopoiesis after 6 wks gestation) • Bone marrow hematopoiesis starts ~5 months of gestation Role of bone -
Engineering of Primary Human B Cells with CRISPR/Cas9 Targeted Nuclease Received: 26 January 2018 Matthew J
www.nature.com/scientificreports OPEN Engineering of Primary Human B cells with CRISPR/Cas9 Targeted Nuclease Received: 26 January 2018 Matthew J. Johnson1,2,3, Kanut Laoharawee1,2,3, Walker S. Lahr1,2,3, Beau R. Webber1,2,3 & Accepted: 23 July 2018 Branden S. Moriarity1,2,3 Published: xx xx xxxx B cells ofer unique opportunities for gene therapy because of their ability to secrete large amounts of protein in the form of antibody and persist for the life of the organism as plasma cells. Here, we report optimized CRISPR/Cas9 based genome engineering of primary human B cells. Our procedure involves enrichment of CD19+ B cells from PBMCs followed by activation, expansion, and electroporation of CRISPR/Cas9 reagents. We are able expand total B cells in culture 10-fold and outgrow the IgD+ IgM+ CD27− naïve subset from 35% to over 80% of the culture. B cells are receptive to nucleic acid delivery via electroporation 3 days after stimulation, peaking at Day 7 post stimulation. We tested chemically modifed sgRNAs and Alt-R gRNAs targeting CD19 with Cas9 mRNA or Cas9 protein. Using this system, we achieved genetic and protein knockout of CD19 at rates over 70%. Finally, we tested sgRNAs targeting the AAVS1 safe harbor site using Cas9 protein in combination with AAV6 to deliver donor template encoding a splice acceptor-EGFP cassette, which yielded site-specifc integration frequencies up to 25%. The development of methods for genetically engineered B cells opens the door to a myriad of applications in basic research, antibody production, and cellular therapeutics. -
B-Helper Neutrophils in Regional Lymph Nodes Correlate with Improved Prognosis in Patients with Head and Neck Cancer
cancers Article B-Helper Neutrophils in Regional Lymph Nodes Correlate with Improved Prognosis in Patients with Head and Neck Cancer Ekaterina Pylaeva 1,† , Irem Ozel 1,† , Anthony Squire 2, Ilona Spyra 1, Charlotte Wallner 1, Magdalena Korek 1, Georg Korschunow 1, Maksim Domnich 1 , Elena Siakaeva 1, Moritz Goetz 3, Agnes Bankfalvi 3, Stephan Lang 1,4, Benjamin Kansy 1,4,*,‡ and Jadwiga Jablonska 1,4,*,‡ 1 Department of Otorhinolaryngology, University Hospital Essen, University Duisburg-Essen, 45147 Essen, Germany; [email protected] (E.P.); [email protected] (I.O.); [email protected] (I.S.); [email protected] (C.W.); [email protected] (M.K.); [email protected] (G.K.); [email protected] (M.D.); [email protected] (E.S.); [email protected] (S.L.) 2 Institute of Experimental Immunology and Imaging, University Hospital Essen, University Duisburg-Essen, 45141 Essen, Germany; [email protected] 3 Institute of Pathology, University Hospital Essen, University of Duisburg-Essen, 45147 Essen, Germany; [email protected] (M.G.); [email protected] (A.B.) 4 German Cancer Consortium (DKTK) Partner Site Düsseldorf/Essen, 45147 Essen, Germany * Correspondence: [email protected] (B.K.); [email protected] (J.J.) † These authors contributed equally. ‡ These authors contributed equally. Simple Summary: Neutrophils exhibit multiple functions during cancer progression and are believed Citation: Pylaeva, E.; Ozel, I.; Squire, to regulate adaptive immune responses to cancer. In addition to their interactions with T cells in A.; Spyra, I.; Wallner, C.; Korek, M.; this context, these cells are also believed to interact with B cells. -
B Cell Responses: Plasmablasts Walk the Line
RESEARCH HIGHLIGHTS B CELL RESPONSES Plasmablasts walk the line During an adaptive immune patterns in lymph nodes. Following molecule intercellular adhesion response, long-lived antibody- immunization with specific antigen, molecule 1 (ICAM1) in plasmablast producing plasma cells are generated YFP+ cells mainly aggregated in migration. Both YFP+ and naive in T cell-dependent germinal centres. the medulla of the lymph node but B cells migrated on ICAM1-coated Plasma cells subsequently localize to could also be found in the B and glass surfaces, but only naive B cells the lymph node medullary chords, T cell zones and at the border of required Gαi-signalling for this move- but their migration to these sites has germinal centres. By contrast, naive ment. In addition, naive B cells and never been directly observed. A study B cells were predominantly localized plasma blasts had different migratory in Immunity has now reported in B cell follicles. behaviour on the ICAM1-coated sur- unique migratory behaviour for their When the migratory patterns faces; naive B cells showed frequent precursors, plasmablasts; these cells of the different populations were detachment and reattachment to the traverse the lymph node in a linear observed in situ using time-lapse substrate, but YFP+ cells migrated in manner and, surprisingly, do not two-photon intravital microscopy, a steady, amoeboid manner. + require Gαi-coupled receptor YFP cells in the medullary chords Interestingly, in assays carried signalling to migrate. were found to be mainly stationary, out in vivo and in vitro, the authors The transcriptional repressor but YFP+ cells in the follicles were reported an inverse correlation B lymphocyte-induced maturation highly motile. -
An Overview of B Cells – from Discovery to Therapy Mini Review
An Overview of B Cells – from Discovery to Therapy Mini Review Immunology In the past two decades, significant advances have been made in B cell biology. These critical immune cells remain an active area of research particularly because disruption of B cell development or function results in a number of autoimmune diseases and malignancies. In addition to producing antibodies, B cells are professional antigen presenting cells that can present antigens to T cells to generate effective immune responses. B cells are however, a heterogeneous population of cells at different stages of maturation along the lineage, each with unique functional properties. This mini-review provides a brief history of the discovery of B cells, as well as describes the characteristics of each B cell lineage and the processes of B cell development, maturation and activation. Finally, we highlight the application of B cell biology in the development of novel therapeutics for the treatment of B cell mediated diseases. Contents 1. A brief history of the discovery of B cells 2. B cell development and maturation 3. B cell activation and the humoral immune response 4. B cells as therapeutic targets 1. A brief history of the discovery of B cells B cells are an integral part of the adaptive immune response. They represent a distinct lineage, with separate and unique functions from T cells. In addition to producing antibodies, they perform critical immune functions such as generating immunological memory, antigen presentation and regulatory cytokine production. Our current understanding of B cell biology was initiated in 1965 with a landmark study by Max Cooper and Robert Good.