The Adaptive Immune Response B-Cells

Total Page:16

File Type:pdf, Size:1020Kb

The Adaptive Immune Response B-Cells The Adaptive Immune Response B-cells The innate immune system provides immediate protection. The adaptive response takes time to develop and is antigen specific. Activation of B and T lymphocytes Naive Plasma cells Naive ADAPTIVE IMMUNITY The adaptive immune system consists of lymphocytes and their products, including antibodies. The receptors of lymphocytes are much more diverse than those of the innate immune system, but lymphocytes are not inherently specific for microbes, and they are capable of recognizing a vast array of foreign substances. http://www.pathologystudent.com/wp- content/uploads/2010/07/normal-lymphs.jpg There are two types of adaptive Immunity Humoral immunity: mediated by B lymphocytes and their secreted products, antibodies (also called immunoglobulins, Ig) that protects against extracellular microbes and their toxins. Cellular immunity: mediated by T lymphocytes and is responsible for defense against intracellular microbes. content/uploads/2011/05/adoptive_immunity.gif - sheng.com/wp - http://yang Types of Adaptive Immune Reponses Lymphocytes Although lymphocytes appear morphologically unimpressive and similar to one another, they are actually remarkably heterogeneous and specialized in molecular properties and functions. Lymphocytes and other cells involved in immune responses are not fixed in particular tissues (as are cells in most of the organs of the body) but are capable of migrating among lymphoid and other tissues and the vascular and lymphatic circulations. This feature permits lymphocytes to home to any site of infection. In lymphoid organs, different classes of lymphocytes are anatomically segregated in such a way that they interact with one another only when stimulated to do so by encounter with antigens and other stimuli. http://www.nature.com/nri/journal/v12/n1/images/nri3128-f5.jpg Mature lymphocytes that have not encountered the antigen for which they are specific are said to be naive (immunologically inexperienced). After they are activated by recognition of antigens and other signals lymphocytes differentiate into: effector cells, which perform the function of eliminating microbes. F1.jpg - 873 - memory cells, which live in a state of heightened awareness and are better able to combat the microbe in case it returns. http://www.nature.com/ni/journal/v5/n9/images/ni0904 http://www.nature.com/nri/journal/v7/n12/images/nri2204-f1.jpg B Lymphocytes B lymphocytes develop from precursors in the bone marrow. Mature B cells constitute 10% to 20% of the circulating peripheral lymphocyte population and are also present in peripheral lymphoid tissues such as lymph nodes, spleen, and mucosa-associated lymphoid tissues. B cells recognize antigen via the B-cell antigen receptor complex. Membrane-bound antibodies called IgM and IgD, present on the surface of all mature, naive B cells, are the antigen-binding component of the B-cell receptor complex. Each B-cell receptor has a unique antigen specificity, derived from RAG- mediated rearrangements of Ig genes. After stimulation by antigen and other signals, B cells develop into plasma cells that secrete antibodies, the mediators of humoral immunity. http://theadventuresofbecky.files.wordpress.com/ http://cytochemistry.net/cell- 2010/03/plasma-cell-100x-website-arrow.jpg biology/medical/06_016.jpg http://www.nature.com/nri/journal/v5/n3/images/nri1572-f1.jpg Immunoglobulins (cont.) • Biologic properties of immunoglobulin domains . Ch3 - cytotrophic reactions involving: • macrophages and monocytes • heterologous mast cells • cytotoxic killer cells • B cells . Ch2 • binding complement • control of catabolic rate . Vh/Vl • antigen binding B Lymphocytes .. γ2 γ4 ε α 2 3' (DNA) µ δ γ3 γ1 Ψε α 1 Ψγ Germline V V V D D D J J J V V V D D J J µ Rearranged V V V D J J µ V D J J µ 1° Transcript V D J µ µ-mRNA 44 Variable (V) gene segments,[2] plus 27 Diversity (D) gene segments and 6 Joining (J) gene segments.[3] The light chains also possess 2 Constant (Cμ and Cδ) gene segments and numerous V and J gene segments, but do not have D gene segments. DNA rearrangement causes one copy of each type of gene segment to go in any given lymphocyte, generating an enormous antibody repertoire; roughly 3×1011 combinations are possible, although some are removed due to self reactivity. (https://en.wikipedia.org/wiki/V(D)J_recombination) B Lymphocytes J Hind III . µ 3' GermlineDNA VDJ µ Allele A DJ B cell leukemia µ AlleleB Germline Leukemia Normal B A J probe http://4.bp.blogspot.com/- IXXEpj_bFg8/T_QO506s1lI/AAAAAAAAAEc/pEUu2wprOhU/s1600/ig+ge ne+in+b+cell+differentiation.png f1.gif - http://www.nature.com/nri/journal/v2/n2/images/nri726 http://www.cellsignal.com/reference/pathway/images/B_Cell_Receptor.jpg In addition to membrane Ig, the B-cell antigen receptor complex contains a heterodimer of two invariant proteins called Igα and Igβ. B cells also express several other molecules that are essential for their responses. These include complement receptors, Fc receptors, and CD40. Upon activation, B lymphocytes proliferate and then differentiate into plasma cells that secrete different classes of antibodies with distinct functions (Fig. 6-12). Upon activation, B lymphocytes proliferate and then differentiate into plasma cells that secrete different classes of antibodies with distinct functions (Fig. 6-12). Many polysaccharide and lipid antigens have multiple identical antigenic determinants (epitopes) that are able to engage many antigen receptor molecules on each B cell and initiate the process of B-cell activation. Typical globular protein antigens are not able to bind to many antigen receptors, and the full response of B cells to protein antigens requires help from CD4+ T cells. B cells ingest protein antigens into vesicles, degrade them, and display peptides bound to MHC molecules for recognition by helper T cells. The helper T cells express CD40L and secrete cytokines, which work together to activate the B cells. http://upload.wikimedia.org/wikipedia/commons/thumb/f/f7/B_cell_activation.png/300px-B_cell_activation.png Immunoglobulins • IgG, IgM and IgA constitute 95% of serum immunoglobulins • IgE trace, IgD B cell membrane associated • Monomeric IgM on B cell surface constitutes B cell receptor • B cell antigen receptor complex contains nonpolymorphic transmembrane proteins like the CD3 proteins of TCR, Igα and Igβ Each plasma cell secretes antibodies that have the same antigen binding site as the cell surface antibodies (B-cell receptors) that first recognized the antigen. Polysaccharides and lipids stimulate secretion mainly of IgM antibody. Protein antigens, by virtue of CD40L- and cytokine-mediated helper T-cell actions, induce the production of antibodies of different classes, or isotypes (IgG, IgA, IgE). Cytokines that induce isotype switching include IFN-γ and IL-4. Helper T cells also stimulate the production of antibodies with high affinities for the antigen. This process, called affinity maturation, improves the quality of the humoral immune response. Isotype switching and affinity maturation occur mainly in germinal centers, which are formed by proliferating B cells, especially in helper T cell- dependent responses to protein antigens. http://www.cs.unm.edu/~immsec/html-imm/AFF-MAT1.JPG Helper T cells are required for efficient isotype switching, affinity maturation and generation of long lived memory B cells Signal 2 Signal 1 Antibodies bind to microbes and prevent them from infecting cells, thus “neutralizing” the microbes. IgG antibodies coat (“opsonize”) microbes and target them for phagocytosis, since phagocytes (neutrophils and macrophages) express receptors for the Fc tails of IgG. IgG and IgM activate the complement system by the classical pathway, and complement products promote phagocytosis and destruction of microbes. The production of most opsonizing and complement-fixing IgG antibodies is stimulated by TH1 helper cells, which respond to many bacteria and viruses; thus, the protective response to most bacteria and viruses is driven by TH1 cells. http://classconnection.s3.amazonaws.com/817/flashcards/995817/jpg/formation_of_secretory_iga1323598120594.jpg http://classconnection.s3.amazonaws.com/799/flashcards/1565799/png/capture1337446126520.png http://faculty.ccbcmd.edu/courses/bio141/lecguide/unit5/intro/gensteps/images/u3fg18b.jpg Some antibodies serve special roles at particular anatomic sites. IgA is secreted from mucosal epithelia and neutralizes microbes in the lumens of the respiratory and gastrointestinal tracts (and other mucosal tissues). IgG is actively transported across the placenta and protects the newborn until the immune system becomes mature. IgE and eosinophils cooperate to kill parasites, mainly by release of eosinophil granule contents that are toxic to the worms. TH2 cells secrete cytokines that stimulate the production of IgE and activate eosinophils, and thus the response to helminths is orchestrated by TH2 cells. http://faculty.ccbcmd.edu/courses/bio141/lecguide/unit5/humoral/5classes/images/u3fig2t.jpg Most circulating IgG antibodies have half-lives of about 3 weeks. Some antibody-secreting plasma cells migrate to the bone marrow and live for years, continuing to produce low levels of antibodies. The majority of effector lymphocytes induced by an infectious pathogen die by apoptosis after the microbe is eliminated, thus returning the immune system to its basal resting state, called homeostasis. The initial activation of lymphocytes also generates long-lived memory cells, which may survive for years after the infection. Memory cells are an expanded pool of antigen-specific lymphocytes (more numerous than the naive cells specific for any antigen that are present before encounter with that antigen), and that respond faster and more effectively when re-exposed to the antigen than do naive cells. This is why the generation of memory cells is an important goal of vaccination. http://www.nature.com/nri/journal/v3/n10/images/nri1201-i1.jpg http://course1.winona.edu/kbates/Immunology/images/figure_06_20.jpg http://legacy.owensboro.kctcs.edu/gcaplan/anat2/notes/Secondary-lymph-follicle-.jpg .
Recommended publications
  • The Ligands for Human Igg and Their Effector Functions
    antibodies Review The Ligands for Human IgG and Their Effector Functions Steven W. de Taeye 1,2,*, Theo Rispens 1 and Gestur Vidarsson 2 1 Sanquin Research, Dept Immunopathology and Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, 1066 CX Amsterdam, The Netherlands; [email protected] 2 Sanquin Research, Dept Experimental Immunohematology and Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, 1066 CX Amsterdam, The Netherlands; [email protected] * Correspondence: [email protected] Received: 26 March 2019; Accepted: 18 April 2019; Published: 25 April 2019 Abstract: Activation of the humoral immune system is initiated when antibodies recognize an antigen and trigger effector functions through the interaction with Fc engaging molecules. The most abundant immunoglobulin isotype in serum is Immunoglobulin G (IgG), which is involved in many humoral immune responses, strongly interacting with effector molecules. The IgG subclass, allotype, and glycosylation pattern, among other factors, determine the interaction strength of the IgG-Fc domain with these Fc engaging molecules, and thereby the potential strength of their effector potential. The molecules responsible for the effector phase include the classical IgG-Fc receptors (FcγR), the neonatal Fc-receptor (FcRn), the Tripartite motif-containing protein 21 (TRIM21), the first component of the classical complement cascade (C1), and possibly, the Fc-receptor-like receptors (FcRL4/5). Here we provide an overview of the interactions of IgG with effector molecules and discuss how natural variation on the antibody and effector molecule side shapes the biological activities of antibodies. The increasing knowledge on the Fc-mediated effector functions of antibodies drives the development of better therapeutic antibodies for cancer immunotherapy or treatment of autoimmune diseases.
    [Show full text]
  • B Cell Checkpoints in Autoimmune Rheumatic Diseases
    REVIEWS B cell checkpoints in autoimmune rheumatic diseases Samuel J. S. Rubin1,2,3, Michelle S. Bloom1,2,3 and William H. Robinson1,2,3* Abstract | B cells have important functions in the pathogenesis of autoimmune diseases, including autoimmune rheumatic diseases. In addition to producing autoantibodies, B cells contribute to autoimmunity by serving as professional antigen- presenting cells (APCs), producing cytokines, and through additional mechanisms. B cell activation and effector functions are regulated by immune checkpoints, including both activating and inhibitory checkpoint receptors that contribute to the regulation of B cell tolerance, activation, antigen presentation, T cell help, class switching, antibody production and cytokine production. The various activating checkpoint receptors include B cell activating receptors that engage with cognate receptors on T cells or other cells, as well as Toll-like receptors that can provide dual stimulation to B cells via co- engagement with the B cell receptor. Furthermore, various inhibitory checkpoint receptors, including B cell inhibitory receptors, have important functions in regulating B cell development, activation and effector functions. Therapeutically targeting B cell checkpoints represents a promising strategy for the treatment of a variety of autoimmune rheumatic diseases. Antibody- dependent B cells are multifunctional lymphocytes that contribute that serve as precursors to and thereby give rise to acti- cell- mediated cytotoxicity to the pathogenesis of autoimmune diseases
    [Show full text]
  • Structural Features of Human Immunoglobulin G That Determine Isotype-Specitic Differences in Complement Activation by Mi-Hua Tao,* Richard I.F
    Structural Features of Human Immunoglobulin G that Determine Isotype-specitic Differences in Complement Activation By Mi-Hua Tao,* Richard I.F. Smith,* and Sherie L. Morrison*r From the "Department of Microbiology and Molecular Genetics and IThe Molecular Biology Institute, University of California, Los Angeles, California 90024 Summary Although very similar in sequence, the four subclasses of human immunoglobulin G (IgG) differ markedly in their ability to activate complement. Glu318-Lys320-Lys322 has been identified as Downloaded from http://rupress.org/jem/article-pdf/178/2/661/1268014/661.pdf by guest on 30 September 2021 a key binding motif for the first component of complement, Clq, and is present in all isotypes of Ig capable of activating complement. This motif, however, is present in all subclasses of human IgG, including those that show little (IgG2) or even no (IgG4) complement activity. Using point mutants of chimeric antibodies, we have identified specificresidues responsible for the differing ability of the IgG subclasses to fix complement. In particular, we show that Ser at position 331 in 3/4 is critical for determining the inability of that isotype to bind Clq and activate complement. Additionally, we provide further evidence that levels of Clq binding do not necessarily correlate with levels of complement activity, and that Clq binding alone is not sufficient for complement activation. he classical pathway of complement activation is initi- tivation ability and an IgG4 with the hinge of IgG3, although T ated by immune complexes composed of antigen and ei- as flexible as wild-type IgG3, displays no detectable comple- ther IgM or IgG Abs.
    [Show full text]
  • Nasopharyngeal Infection by Streptococcus Pyogenes Requires Superantigen-Responsive Vβ-Specific T Cells
    Nasopharyngeal infection by Streptococcus pyogenes requires superantigen-responsive Vβ-specific T cells Joseph J. Zeppaa, Katherine J. Kaspera, Ivor Mohorovica, Delfina M. Mazzucaa, S. M. Mansour Haeryfara,b,c,d, and John K. McCormicka,c,d,1 aDepartment of Microbiology and Immunology, Schulich School of Medicine & Dentistry, Western University, London, ON N6A 5C1, Canada; bDepartment of Medicine, Division of Clinical Immunology & Allergy, Schulich School of Medicine & Dentistry, Western University, London, ON N6A 5A5, Canada; cCentre for Human Immunology, Western University, London, ON N6A 5C1, Canada; and dLawson Health Research Institute, London, ON N6C 2R5, Canada Edited by Philippa Marrack, Howard Hughes Medical Institute, National Jewish Health, Denver, CO, and approved July 14, 2017 (received for review January 18, 2017) The globally prominent pathogen Streptococcus pyogenes secretes context of invasive streptococcal disease is extremely dangerous, potent immunomodulatory proteins known as superantigens with a mortality rate of over 30% (10). (SAgs), which engage lateral surfaces of major histocompatibility The role of SAgs in severe human infections has been well class II molecules and T-cell receptor (TCR) β-chain variable domains established (5, 11, 12), and specific MHC-II haplotypes are known (Vβs). These interactions result in the activation of numerous Vβ- risk factors for the development of invasive streptococcal disease specific T cells, which is the defining activity of a SAg. Although (13), an outcome that has been directly linked to SAgs (14, 15). streptococcal SAgs are known virulence factors in scarlet fever However, how these exotoxins contribute to superficial disease and and toxic shock syndrome, mechanisms by how SAgs contribute colonization is less clear.
    [Show full text]
  • Clinically-Relevant Monoclonal Antibodies
    ANTIBODIES ISOTYPE FAMILIES Switch natural isotypes Clinically relevant monoclonal antibodies Fine-tuned effector functions Up to 14 different native and engineered isotypes InvivoGen provides a series of clinically relevant antibodies in their original Antibodies against format or with different immunoglobulin isotypes. Our engineered antibodies various targets are designed to adjust their effector functions, including half-life, complement- Anti-hCD20 Anti-hPD1 dependent cytotoxicity (CDC), antibody-dependent cellular cytotoxicity Anti-hCTLA4 Anti-hPD-L1 (ADCC) and antibody-dependent cell phagocytosis (ADCP). The variety of Anti-hEGFR Anti-hTNF-α the immunoglobulin constant regions helps you determine the most suitable Anti-HER2 Anti-hVEGF isotype for your application. WWW.INVIVOGEN.COM/ANTIBODY-ISOTYPES Description Monoclonal antibodies (mAbs) have become a major tool in the treatment of cancer and auto-immune diseases. The efficacy of antibodies is governed by their bifunctional nature. On the one hand, the variable domain of the immunoglobulin, within the fragment of antigen binding (Fab), confers antigen specificity function. On the other hand, the fragment crystallizable region (Fc) in the constant domain of the immunoglobulin triggers antibody-mediated effector functions by engaging a variety of Fc receptors. Antibody isotype switching is a biological process enabling changes in the ability of the antibody to interact with different Fc receptors and thus, reduce or potentiate effector functions. InvivoGen’s antibody isotype families consist of clinically relevant mAbs comprising the same variable domain and the constant domain of various isotypes, therefore differing in their suitability for a given application. Native and engineered isotypes Features of our antibody isotype families • Native isotype antibodies Physiological native isotypes trigger various combinations of Specificities Fragment antigen effector functions that are summarized in the table below.
    [Show full text]
  • The Importance of Using an Isotype Control
    The Importance of Using an Isotype Control White Paper What are Isotype Controls? Isotype control antibodies are essential negative controls for in vivo studies and can play an important role in standard immunoassays, such as flow cytometry and immunohistochemistry (IHC). They match the characteristics of the assay’s primary antibody (e.g. isotype, clonality), but having been raised against antigens known not to be present in common preclinical species (HEL, KLH, etc.), have no target cell/antigen specificity. This provides researchers with a suitable negative control to accurately discriminate between an antibody binding in an antigen-dependent specific manner from non-antigen dependent mAb binding due to Fc receptors (FcR) or other proteins. In the simplest terms, isotype controls help distinguish non- specific background signal from specific antibody signal. Monoclonal, subclass specific (i.e. lambda vs. kappa immunoglobulin) isotype controls provide an especially reliable method that effectively differentiates between specificity versus background in a range of drug development assays. Why is it Important to Use Isotype Controls? Structurally, all antibodies are very similar, with only a small hypervariable region determining antigen specific binding. The rest of the antibody molecule consists of Using an the constant region, where sequences are often shared by antibodies of the same “appropriate isotype. isotype control allows the true The constant regions help determine antibody mechanism of action, by coordinating determination binding to the FcR present on many cell types. FcRs are expressed on a number of different cell types in the immune system, including (but not limited to): of specific vs non-antigen • B lymphocytes specific • follicular dendritic cells binding • natural killer cells across a range • macrophages • neutrophils of in vivo “ studies and • eosinophils Immunoassays • basophils • human platelets • mast cells.
    [Show full text]
  • A Novel Superantigen Isolated from Pathogenic Strains of Streptococcus Pyogenes with Aminoterminal Homology to Staphylococcal Enterotoxins B and C
    A novel superantigen isolated from pathogenic strains of Streptococcus pyogenes with aminoterminal homology to staphylococcal enterotoxins B and C. J A Mollick, … , D Grossman, R R Rich J Clin Invest. 1993;92(2):710-719. https://doi.org/10.1172/JCI116641. Research Article Streptococcus pyogenes (group A Streptococcus) has re-emerged in recent years as a cause of severe human disease. Because extracellular products are involved in streptococcal pathogenesis, we explored the possibility that a disease isolate expresses an uncharacterized superantigen. We screened culture supernatants for superantigen activity with a major histocompatibility complex class II-dependent T cell proliferation assay. Initial fractionation with red dye A chromatography indicated production of a class II-dependent T cell mitogen by a toxic shock-like syndrome (TSLS) strain. The amino terminus of the purified streptococcal superantigen was more homologous to the amino termini of staphylococcal enterotoxins B, C1, and C3 (SEB, SEC1, and SEC3), than to those of pyrogenic exotoxins A, B, C or other streptococcal toxins. The molecule, designated SSA, had the same pattern of class II isotype usage as SEB in T cell proliferation assays. However, it differed in its pattern of human T cell activation, as measured by quantitative polymerase chain reaction with V beta-specific primers. SSA activated human T cells that express V beta 1, 3, 15 with a minor increase of V beta 5.2-bearing cells, whereas SEB activated V beta 3, 12, 15, and 17-bearing T cells. Immunoblot analysis of 75 disease isolates from several localities detected SSA production only in group A streptococci, and found that SSA is apparently confined to only three clonal […] Find the latest version: https://jci.me/116641/pdf A Novel Superantigen Isolated from Pathogenic Strains of Streptococcus pyogenes with Aminoterminal Homology to Staphylococcal Enterotoxins B and C Joseph A.
    [Show full text]
  • 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.
    [Show full text]
  • Structure, Function, and Therapeutic Use of Igm Antibodies
    antibodies Review Structure, Function, and Therapeutic Use of IgM Antibodies Bruce A. Keyt *, Ramesh Baliga, Angus M. Sinclair, Stephen F. Carroll and Marvin S. Peterson IGM Biosciences Inc, 325 East Middlefield Road, Mountain View, CA 94043, USA; [email protected] (R.B.); [email protected] (A.M.S.); [email protected] (S.F.C.); [email protected] (M.S.P.) * Correspondence: [email protected]; Tel.: +1-650-265-6458 Received: 16 September 2020; Accepted: 9 October 2020; Published: 13 October 2020 Abstract: Natural immunoglobulin M (IgM) antibodies are pentameric or hexameric macro- immunoglobulins and have been highly conserved during evolution. IgMs are initially expressed during B cell ontogeny and are the first antibodies secreted following exposure to foreign antigens. The IgM multimer has either 10 (pentamer) or 12 (hexamer) antigen binding domains consisting of paired µ heavy chains with four constant domains, each with a single variable domain, paired with a corresponding light chain. Although the antigen binding affinities of natural IgM antibodies are typically lower than IgG, their polyvalency allows for high avidity binding and efficient engagement of complement to induce complement-dependent cell lysis. The high avidity of IgM antibodies renders them particularly efficient at binding antigens present at low levels, and non-protein antigens, for example, carbohydrates or lipids present on microbial surfaces. Pentameric IgM antibodies also contain a joining (J) chain that stabilizes the pentameric structure and enables binding to several receptors. One such receptor, the polymeric immunoglobulin receptor (pIgR), is responsible for transcytosis from the vasculature to the mucosal surfaces of the lung and gastrointestinal tract.
    [Show full text]
  • Selective Igm Deficiency—An Underestimated Primary Immunodeficiency
    UC Irvine UC Irvine Previously Published Works Title Selective IgM Deficiency-An Underestimated Primary Immunodeficiency. Permalink https://escholarship.org/uc/item/6wg240n5 Journal Frontiers in immunology, 8(SEP) ISSN 1664-3224 Authors Gupta, Sudhir Gupta, Ankmalika Publication Date 2017 DOI 10.3389/fimmu.2017.01056 License https://creativecommons.org/licenses/by/4.0/ 4.0 Peer reviewed eScholarship.org Powered by the California Digital Library University of California REVIEW published: 05 September 2017 doi: 10.3389/fimmu.2017.01056 Selective IgM Deficiency—An Underestimated Primary Immunodeficiency Sudhir Gupta* and Ankmalika Gupta† Program in Primary Immunodeficiency and Aging, Division of Basic and Clinical Immunology, University of California at Irvine, Irvine, CA, United States Although selective IgM deficiency (SIGMD) was described almost five decades ago, it was largely ignored as a primary immunodeficiency. SIGMD is defined as serum IgM levels below two SD of mean with normal serum IgG and IgA. It appears to be more common than originally realized. SIGMD is observed in both children and adults. Patients with SIGMD may be asymptomatic; however, approximately 80% of patients with SIGMD present with infections with bacteria, viruses, fungi, and protozoa. There is an increased frequency of allergic and autoimmune diseases in SIGMD. A number Edited by: of B cell subset abnormalities have been reported and impaired specific antibodies Guzide Aksu, to Streptococcus pneumoniae responses are observed in more than 45% of cases. Ege University, Turkey Innate immunity, T cells, T cell subsets, and T cell functions are essentially normal. Reviewed by: Amos Etzioni, The pathogenesis of SIGMD remains unclear. Mice selectively deficient in secreted IgM University of Haifa, Israel are also unable to control infections from bacterial, viral, and fungal pathogens, and Isabelle Meyts, develop autoimmunity.
    [Show full text]
  • Systemic Autoimmunity Induced by the TLR7/8 Agonist Resiquimod Causes Myocarditis and Dilated Cardiomyopathy in a New Mouse Model of Autoimmune Heart Disease Muneer G
    © 2017. Published by The Company of Biologists Ltd | Disease Models & Mechanisms (2017) 10, 259-270 doi:10.1242/dmm.027409 RESEARCH ARTICLE Systemic autoimmunity induced by the TLR7/8 agonist Resiquimod causes myocarditis and dilated cardiomyopathy in a new mouse model of autoimmune heart disease Muneer G. Hasham1, Nicoleta Baxan2, Daniel J. Stuckey3, Jane Branca1, Bryant Perkins1, Oliver Dent4, Ted Duffy1, Tolani S. Hameed4, Sarah E. Stella4, Mohammed Bellahcene4, Michael D. Schneider4, Sian E. Harding4, Nadia Rosenthal1,4 and Susanne Sattler4,* ABSTRACT disease results from direct target-specific tissue damage due to Systemic autoimmune diseases such as systemic lupus autoreactive effector cells and antibodies, as well as from indirect erythematosus (SLE) and rheumatoid arthritis (RA) show significant damage due to increased systemic levels of inflammatory cytokines heart involvement and cardiovascular morbidity, which can be due to (Abou-Raya and Abou-Raya, 2006; Abusamieh and Ash, 2004; systemically increased levels of inflammation or direct autoreactivity Knockaert, 2007). targeting cardiac tissue. Despite high clinical relevance, cardiac The most common cardiac complication of the prototype systemic damage secondary to systemic autoimmunity lacks inducible rodent autoimmune disease systemic lupus erythematosus (SLE) is models. Here, we characterise immune-mediated cardiac tissue pericarditis, followed by myocarditis or myocardial fibrosis due to damage in a new model of SLE induced by topical application of the infiltration of inflammatory cells (Jastrzebską et al., 2013). Toll-like receptor 7/8 (TLR7/8) agonist Resiquimod. We observe a Myocarditis may be idiopathic, infectious or autoimmune in origin. cardiac phenotype reminiscent of autoimmune-mediated dilated Inflammation may resolve or persist and lead to cardiac remodelling, cardiomyopathy, and identify auto-antibodies as major contributors ventricular dilation with normal or reduced left ventricular wall to cardiac tissue damage.
    [Show full text]
  • Immunology: Antibody Basics 2
    John A. Burns School of Medicine JABSOM e-Learning for Basic Sciences e-Learning To navigate: 1 1. Yellow navigation bar 2 Immunology: Antibody Basics 2. Back and Fwd buttons Estimated Learning Time: 30 min. 3 4 Back Fwd 5 One :: General Structure 6 7 Identify the Parts of an Antibody 8 Two :: Isotypes 9 Identify Antibody Isotypes 10 [ Start Now! ] 11 Three :: Function 12 Match Antibody Functions With Isotypes 13 14 Four :: Diversity 15 Explain Antibody Diversity 16 17 Antibody 18 Advice 19 20 21 Allow Hi! 22 me to be your Ctrl + L 23 Command + L guide... find me 24 FULL SCREEN at the bottom 25 in Adobe Acrobat of each page! 26 Contributors William L. Gosnell, Ph.D. Software Requirements: Kenton J. Kramer, Ph.D. Click to download Karen M. Yamaga, Ph.D. the latest versions Department of Tropical Medicine, Medical Microbiology and Pharmacology JABSOM John A. Burns School of Medicine e-Learning e-Learning for Basic Sciences OVERVIEW 1 2 3 Contents 4 5 instructional By the end of this module you should be This One :: General Structure 6 module was designed with you able to: Identify the Parts of an Antibody Page 3 7 in mind. Understanding antibody 1. Identify the parts of an antibody. basics will help you understand 2. Identify antibody isotypes. Two :: Isotypes 8 immunology concepts that are 3. Match antibody functions with isotypes. Identify Antibody Isotypes Page 9 9 necessary to pass USMLE board 4. Explain antibody diversity from 10 exams - the first step on your way somatic recombination. to becoming a doctor.
    [Show full text]