DOCSLIB.ORG

Humoral Immunity and Complement Humoral Immunity B Cell Antigens

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Humoral Immunity and Complement Humoral Immunity B Cell Antigens Humoral Immunity Humoral Immunity and Complement Transfer of non-cell components of blood-- Robert Beatty antibodies, complement MCB150 Humoral immunity = antibody mediated B Cell Activation of T-dependent antigens B cell Antigens T cell dependent B cell antigens T cell independent Majority of antigens. Do not require thymus. Most protein antigens. No memory. T cell help required for B cell activation and antibody production. T-cell dependent antigens T-cell independent antigens 1 B Cell Activation T-dependent antigens Location of B Cell Activation Antigen activated B cells remain in T cell zones of LN. Linked Recognition Maximize contact of Need T cell epitope along with B cell epitope to B cells with T cells. get antibody response. B cells get help from T cells, help = CD40Ligand and IL-4. Clonal proliferation In Follicles Isotype Switching Affinity maturation Somatic hypermutation 2 T cell Independent Antigens B cell mitogens (e.g. LPS) B-1 cells At low levels normal immune response to LPS Activated by repeating CHO epitopes that provide crosslinking At high levels LPS can cause non-antigen specific to induce antigen uptake and activation. activation of B cells. Mitogen effect Antigen specific immune response Lower affinity, lower numbers, no memory. Primarily IgM. Antibody Effector Functions Opsonization Neutralization Antibody Effector Functions Enhancement of phagocytosis Neutralizing abs block active site for adherence, entry into host cell, or active site of toxin Neutralizing antibodies are usually high affinity and primarily IgG. 3 Antibody-dependent cell-mediated Complement Activation cytotoxicity (ADCC) Antibody Effector Functions Antibody Effector Functions Antibody binds to pathogen or infected target cell. Fc portion of antibody binds to Fc receptors of a cytotoxic cell. Antibody binds to antigen…….complement binds. Kill, kill, kill……. Which we will talk about in great detail---- very shortly. ADCC of target cell with bound antibody by activated NK cells Control of Antibody Effector Functions Location of Antibody Isotype Influences Function Fc Receptors IgA Mucosal Fc γ Receptors – opsonization and ADCC IgG Tissues/blood crosses placenta FcRα1 for IgA – opsonization and ADCC IgE Parasitic, mast cells FcεR1 on Mast cells – can prolong life of IgE (role in hypersensitivity) IgM Peritoneum, tissues, 4 Complement Complement Classical Pathway Pathways C1q binds to 1 IgM molecule OR 2 IgG molecules Complement Classical Pathway Classical Pathway Q: Why don't Complement proteins bind to antibodies in serum or lymph fluid? C1q binds to 2 IgG molecules Staple form of IgM Planar form of IgM Answer: Antibodies only expose Fc domain for Complement binding when bound to antigen. 5 C1qr2s2 Classical Pathway Classical Pathway Once C1q binds to antibodies it provides site for serine proteases C1s and C1r to bind. C1 cleaves C4 and C2. Full C1 molecule is made of 1 C1q with C4b and C2b stay bound to cell surface 2C1r and 2 C1s molecules. to form C3 convertase (cleaving C3). Formation of Membrane Attack Complex Membrane Attack Complex (MAC) Once C5b is bound then C6, C7, C8 all bind to attract multiple C9s. C9is pore-forming protein. 6 Alternate Pathway C3 spontaneously cleaves. C3b is bound. Factor B binds C3b-B is cleaved by D forms C3bBb. C3bBb is a C3 convertase stabilized by Properdin. Amplification making more C3b. C3bBb3b is C5 convertase. Biological Functions of C' Biological Functions of C' Lysis of pathogen of infected cell Opsonization Complement Receptors initiate other functions of C' CRs vs FcRs 7 Biological Functions of C' Biological Functions of C' Clearance of Immune complexes Inflammation Proteins that Regulate and Inhibit Proteins that Regulate and Inhibit Complement Complement 8.
Load more

Recommended publications
  • 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.
    [Show full text]
  • Discussion of Natural Killer Cells and Innate Immunity
    Discussion of natural killer cells and innate immunity Theresa L. Whiteside, Ph.D. University of Pittsburgh Cancer Institute Pittsburgh, PA 15213 Myths in tumor immunology • Cancer cells are ignored by the immune system • Immune responses are directed only against “unique” antigens expressed on tumor cells • Tumor-specific T cells alone are sufficient for tumor regression • Tumor are passive targets for anti-tumor responses Tumor/Immune Cells Interactions Tumor cell death C G DC M TUMOR NK Th B Tc Ab Ag Ag/Ab complex NK cells as anti-tumor effectors • LGL, no TCR, express FcγRIII, other activating receptors and KIRs • Spare normal cells but kill a broad range of tumor cells ex vivo by at least two different mechanisms • Produce a number of cytokines (IFN-γ, TNF-α) • Constitutively express IL-2Rβγ and rapidly respond to IL-2 and also to IL-15 and IFNα/β • Regulated by a balance of inhibitory receptors specific for MHC class I antigens and activating signals • NK-DC interactions at sites of inflammation Heterogeneity of human NK cells • Every NK cell expresses at least one KIR that recognizes a self MHC class I molecule • Two functionally distinct subsets: 1) 90% CD56dimCD16bright , highly cytotoxic, abundant KIR expression, few cytokines 2) 10% CD56brightCD16dim/neg, produce cytokines, poorly cytotoxic, low KIR expression Expression of activating and inhibitory receptors on NK cells Interaction with CD56 Interaction with MHC ligands non-MHC ligands KIR CD16 CD2 CD94/NKG2A/B β2 NKp46, 44, 30 CD94/NKG2C/E NK Cell 2B4 NKG2D Lair1 LIR/ILT A
    [Show full text]
  • Adoptive Cell Therapy Using Engineered Natural Killer Cells
    Bone Marrow Transplantation (2019) 54:785–788 https://doi.org/10.1038/s41409-019-0601-6 REVIEW ARTICLE Adoptive cell therapy using engineered natural killer cells Katayoun Rezvani1 © The Author(s), under exclusive licence to Springer Nature Limited 2019 Abstract The generation of autologous T cells expressing a chimeric antigen receptor (CAR) have revolutionized the field of adoptive cellular therapy. CAR-T cells directed against CD19 have resulted in remarkable clinical responses in patients affected by B-lymphoid malignancies. However, the production of allogeneic CAR-T cells products remains expensive and clinically challenging. Moreover, the toxicity profile of CAR T-cells means that currently these life-saving treatments are only delivered in specialized centers. Therefore, efforts are underway to develop reliable off-the-shelf cellular products with acceptable safety profiles for the treatment of patients with cancer. Natural killer (NK) cells are innate effector lymphocytes with potent antitumor activity. The availability of NK cells from multiple sources and their proven safety profile in the allogeneic setting positions them as attractive contenders for cancer immunotherapy. In this review, we discuss advantages and potential drawbacks of using NK cells as a novel cellular therapy against hematologic malignancies, as well as strategies 1234567890();,: 1234567890();,: to further enhance their effector function. Introduction need for inpatient care may ultimately be economically unviable for many health care systems; (iii) the longer time Adoptive cell therapy has become a powerful treatment that is required to generate CAR T-cells may result in modality for advanced cancers refractory to conventional unavoidable delays in therapy, especially for patients with therapy.
    [Show full text]
  • COVID-19 Natural Immunity
    COVID-19 natural immunity Scientific brief 10 May 2021 Key Messages: • Within 4 weeks following infection, 90-99% of individuals infected with the SARS-CoV-2 virus develop detectable neutralizing antibodies. • The strength and duration of the immune responses to SARS-CoV-2 are not completely understood and currently available data suggests that it varies by age and the severity of symptoms. Available scientific data suggests that in most people immune responses remain robust and protective against reinfection for at least 6-8 months after infection (the longest follow up with strong scientific evidence is currently approximately 8 months). • Some variant SARS-CoV-2 viruses with key changes in the spike protein have a reduced susceptibility to neutralization by antibodies in the blood. While neutralizing antibodies mainly target the spike protein, cellular immunity elicited by natural infection also target other viral proteins, which tend to be more conserved across variants than the spike protein. The ability of emerging virus variants (variants of interest and variants of concern) to evade immune responses is under investigation by researchers around the world. • There are many available serologic assays that measure the antibody response to SARS-CoV-2 infection, but at the present time, the correlates of protection are not well understood. Objective of the scientific brief This scientific brief replaces the WHO Scientific Brief entitled “’Immunity passports’ in the context of COVID-19”, published 24 April 2020.1 This update is focused on what is currently understood about SARS-CoV-2 immunity from natural infection. More information about considerations on vaccine certificates or “passports”will be covered in an update of WHO interim guidance, as requested by the COVID-19 emergency committee.2 Methods A rapid review on the subject was undertaken and scientific journals were regularly screened for articles on COVID-19 immunity to ensure to include all large and robust studies available in the literature at the time of writing.
    [Show full text]
  • Targeting Dendritic Cells with Antigen-Delivering Antibodies for Amelioration of Autoimmunity in Animal Models of Multiple Sclerosis and Other Autoimmune Diseases
    antibodies Review Targeting Dendritic Cells with Antigen-Delivering Antibodies for Amelioration of Autoimmunity in Animal Models of Multiple Sclerosis and Other Autoimmune Diseases Courtney A. Iberg and Daniel Hawiger * Department of Molecular Microbiology and Immunology, Saint Louis University School of Medicine, Doisy Research Center, 1205 Carr Lane, St. Louis, MO 63104, USA; [email protected] * Correspondence: [email protected] Received: 31 March 2020; Accepted: 30 April 2020; Published: 15 June 2020 Abstract: The specific targeting of dendritic cells (DCs) using antigen-delivering antibodies has been established to be a highly efficient protocol for the induction of tolerance and protection from autoimmune processes in experimental autoimmune encephalomyelitis (EAE), a model of multiple sclerosis (MS), as well as in some other animal disease models. As the specific mechanisms of such induced tolerance are being investigated, the newly gained insights may also possibly help to design effective treatments for patients. Here we review approaches applied for the amelioration of autoimmunity in animal models based on antibody-mediated targeting of self-antigens to DCs. Further, we discuss relevant mechanisms of immunological tolerance that underlie such approaches, and we also offer some future perspectives for the application of similar methods in certain related disease settings such as transplantation. Keywords: dendritic cells; tolerance; antigen targeting; chimeric antibodies; autoimmunity; multiple sclerosis; diabetes 1. Introduction Over one hundred years ago, Paul Ehrlich coined the term “horror autotoxicus” to define an immune attack against an organism’s healthy tissues [1]. Since then, our knowledge of the complex mechanisms of the immune system as well as our understanding of the pathogenesis of specific autoimmune diseases have grown tremendously.
    [Show full text]
  • Eosinophil Response Against Classical and Emerging
    REVIEWS Eosinophil Response Against Classical and Emerging Respiratory Viruses: COVID-19 Rodrigo-Muñoz JM1,2, Sastre B1,2, Cañas JA1,2, Gil-Martínez M1, Redondo N1, del Pozo V1,2 1Immunology Department, Instituto de Investigación Sanitaria (IIS) Fundación Jiménez Díaz, Madrid, Spain 2CIBER de Enfermedades Respiratorias (CIBERES), Madrid, Spain J Investig Allergol Clin Immunol 2021; Vol. 31(2): 94-107 doi: 10.18176/jiaci.0624 Abstract Eosinophils were discovered more than 140 years ago. These polymorphonuclear leukocytes have a very active metabolism and contain numerous intracellular secretory granules that enable multiple effects on both health and disease status. Classically, eosinophils have been considered important immune cells in the pathogenesis of inflammatory processes (eg, parasitic helminth infections) and allergic or pulmonary diseases (eg, asthma) and are always associated with a type 2 immune response. Furthermore, in recent years, eosinophils have been linked to the immune response by conferring host protection against fungi, bacteria, and viruses, which they recognize through several molecules, such as toll-like receptors and the retinoic acid–inducible gene 1–like receptor. The immune protection provided by eosinophils is exerted through multiple mechanisms and properties. Eosinophils contain numerous cytoplasmatic granules that release cationic proteins, cytokines, chemokines, and other molecules, all of which contribute to their functioning. In addition to the competence of eosinophils as effector cells, their capabilities as antigen-presenting cells enable them to act in multiple situations, thus promoting diverse aspects of the immune response. This review summarizes various aspects of eosinophil biology, with emphasis on the mechanisms used and roles played by eosinophils in host defence against viral infections and response to vaccines.
    [Show full text]
  • LECTURE 05 Acquired Immunity and Clonal Selection
    LECTURE: 05 Title: ACQUIRED "ADAPTIVE" IMMUNITY & CLONAL SELECTION THEROY LEARNING OBJECTIVES: The student should be able to: • Recognize that, acquired or adaptive immunity is a specific immunity. • Explain the mechanism of development of the specific immunity. • Enumerate the components of the specific immunity such as A. Primary immune response. B. Secondary immune response • Explain the different phases that are included in the primary and secondary immune responses such as: A. The induction phase. B. Exponential phase. C. Steady phase. D. Decline phase. • Compare between the phases of the primary and secondary immune responses. • Determine the type of the immunoglobulins involved in each phase. • Determine which immunoglobulin is induced first and, that last longer. • Enumerate the characteristics of the specific immunity such as: A. The ability to distinguish self from non-self. B. Specificity. C. Immunological memory. • Explain naturally and artificially acquired immunity (passive, and active). • Explain the two interrelated and independent mechanisms of the specific immune response such as : A. Humoral immunity. B. Cell-mediated (cellular) immunity. • Recognize that, the specific immunity is not always protective, for example; sometimes it causes allergies (hay fever), or it may be directed against one of the body’s own constituents, resulting in autoimmunity (thyroditis). LECTURE REFRENCE: 1. TEXTBOOK: ROITT, BROSTOFF, MALE IMMUNOLOGY. 6th edition. Chapter 2. pp. 15-31 2. TEXTBOOK: ABUL K. ABBAS. ANDREW H. LICHTMAN. CELLULAR AND MOLECULAR IMMUNOLOGY. 5TH EDITION. Chapter 1. pg 3-12. 1 ACQUIRED (SPECIFIC) IMMUNITY INTRODUCTION Adaptive immunity is created after an interaction of lymphocytes with particular foreign substances which are recognized specifically by those lymphocytes.
    [Show full text]
  • Innate Immunity and Inflammation
    ISBTc ‐ Primer on Tumor Immunology and Biological Therapy of Cancer InnateInnate ImmunityImmunity andand InflammationInflammation WillemWillem Overwijk,Overwijk, Ph.D.Ph.D. MDMD AndersonAnderson CancerCancer CenterCenter CenterCenter forfor CancerCancer ImmunologyImmunology ResearchResearch Houston,Houston, TXTX www.allthingsbeautiful.com InnateInnate ImmunityImmunity andand InflammationInflammation • Definitions • Cells and Molecules • Innate Immunity and Inflammation in Cancer • Bad Inflammation • Good Inflammation • Therapeutic Implications InnateInnate ImmunityImmunity andand InflammationInflammation • Definitions • Cells and Molecules • Innate Immunity and Inflammation in Cancer • Bad Inflammation • Good Inflammation • Therapeutic Implications • Innate Immunity: Immunity that is naturally present and is not due to prior sensitization to an antigen; generally nonspecific. It is in contrast to acquired/adaptive immunity. Adapted from Merriam‐Webster Medical Dictionary • Innate Immunity: Immunity that is naturally present and is not due to prior sensitization to an antigen; generally nonspecific. It is in contrast to acquired/adaptive immunity. • Inflammation: a local response to tissue injury – Rubor (redness) – Calor (heat) – Dolor (pain) – Tumor (swelling) Adapted from Merriam‐Webster Medical Dictionary ““InnateInnate ImmunityImmunity”” andand ““InflammationInflammation”” areare vaguevague termsterms •• SpecificSpecific cellcell typestypes andand moleculesmolecules orchestrateorchestrate specificspecific typestypes ofof inflammationinflammation
    [Show full text]
  • 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.
    [Show full text]
  • Antibody-Antigen Interaction (Anti-Nucleotide Antibody/Anti-Hapten Antibody) ROBERT J
    Proc. Nati. Acad. Sci. USA Vol. 77, No. 12, pp. 7410-7414, December 1980 Immunology Anti-AMP antibody precipitation of multiply adenylylated forms of glutamine synthetase from Escherichia coli: A model relating both concentration and density of antigenic sites with the antibody-antigen interaction (anti-nucleotide antibody/anti-hapten antibody) ROBERT J. HOHMAN*, SUE Goo RHEEt, AND EARL R. STADTMANtt tLaboratory of Biochemistry, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20205; and *Department of Microbiology, University of Maryland, College Park, Maryland 20742 Contributed by E. R. Stadtman, September 12, 1980 ABSTRACT Sheep antibodies directed against an AMP- ylylated forms of GS to determine the effects of the total con- bovine serum albumin conjugate exhibit highly specific binding centration of antigenic determinants, density of determinants toward AMP. These antibodies bind to the AMP moiety of ad- enylylated glutamine synthetase [-glutamate:ammonia ligase per antigen, and the topological distribution of antigenic de- (ADP-forming), EC 6.3.1.2] from Escherichia coli and to no other terminants, on the initial antibody-antigen binding, lattice antigenic determinant on the protein. E. coli glutamine syn- formation, and immunoprecipitation.§ Some of the experi- thetase can exist in variously modified (isomeric) forms that mental data were presented in an earlier preliminary com- differ with respect to the number (0-12) and the distribution of munication (3). identically adenylylated subunits [Ciardi, J. E., Cimino, F. & Stadtman, E. R. (1973) Biochemistry 12,432143301. Using this MATERIALS AND METHODS enzyme, together with the AMP-specific antibodies, we have investigated the effects of the total concentration, population Purification and Assay of GS.
    [Show full text]
  • A Role of Inflammation and Immunity in Essential Hypertension—Modeled and Analyzed Using Petri Nets
    International Journal of Molecular Sciences Article A Role of Inflammation and Immunity in Essential Hypertension—Modeled and Analyzed Using Petri Nets Dorota Formanowicz 1 , Agnieszka Rybarczyk 2,3 , Marcin Radom 2,3 and Piotr Formanowicz 2,3,* 1 Department of Clinical Biochemistry and Laboratory Medicine, Poznan University of Medical Sciences, 60-806 Poznan, Poland; [email protected] 2 Institute of Computing Science, Poznan University of Technology, 60-965 Poznan, Poland; [email protected] (A.R.); [email protected] (M.R.) 3 Institute of Bioorganic Chemistry, Polish Academy of Sciences, 61-704 Poznan, Poland * Correspondence: [email protected] Received: 15 April 2020; Accepted: 5 May 2020; Published: 9 May 2020 Abstract: Recent studies have shown that the innate and adaptive immune system, together with low-grade inflammation, may play an important role in essential hypertension. In this work, to verify the importance of selected factors for the development of essential hypertension, we created a Petri net-based model and analyzed it. The analysis was based mainly on t-invariants, knockouts of selected fragments of the net and its simulations. The blockade of the renin-angiotensin (RAA) system revealed that the most significant effect on the emergence of essential hypertension has RAA activation. This blockade affects: (1) the formation of angiotensin II, (2) inflammatory process (by influencing C-reactive protein (CRP)), (3) the initiation of blood coagulation, (4) bradykinin generation via the kallikrein-kinin system, (5) activation of lymphocytes in hypertension, (6) the participation of TNF alpha in the activation of the acute phase response, and (7) activation of NADPH oxidase—a key enzyme of oxidative stress.
    [Show full text]
  • (COVID-19): PCR, Antigen, and Antibody Tests There Are Three Types of Tests Available for SARS-Cov-2, the Virus
    Coronavirus 2019 (COVID-19): PCR, Antigen, and Antibody Tests There are three types of tests available for SARS-CoV-2, the virus that causes COVID-19: polymerase chain reaction (PCR), antigen, and antibody (serology) testing. PCR and antigen tests detect whether a person is currently infected, and serology detects whether a person had an infection in the past. All positive and negative test results for SARS-CoV2 are reportable in the District of Columbia. This document provides information about each type of test. Topic PCR Test Antigen Test Antibody (Serology) Test Why is the test PCR tests look for pieces of Antigen tests look for pieces of Serology looks for antibodies1 against used? genetic material of SARS-CoV-2, proteins that make up the SARS- SARS-CoV-2, the virus that causes the virus that causes COVID-19, in CoV-2 virus, the virus that causes COVID-19, in the blood to determine if the nose, throat, or other areas in COVID-19, to determine if the person there was a past infection. the respiratory tract to determine if has an active (i.e., current) infection. the person has an active (i.e., current) infection. How is the test In most cases, a nasopharyngeal In most cases, a nasopharyngeal In most cases, a blood sample is taken performed? or nasal swab is taken by a nasal swab is taken by a healthcare and sent to a lab for testing. healthcare provider and tested; provider and tested. Most often the however, oral swabs and saliva test can be run while you wait, and can be used.
    [Show full text]