MLS 325 Acquired immunity.ppt

Investigation strategies and methods Acquired immunity MLS 325 Laboratory Training for FieldEEpidemiologists P I D E M I C A L E R T A N D R E S P O N S E  D...

Investigation strategies and methods Acquired immunity MLS 325 Laboratory Training for FieldEEpidemiologists P I D E M I C A L E R T A N D R E S P O N S E  Definitions Immune system = cells, tissues, and molecules that mediate resistance to infections Immunology = study of structure and function of the immune system Immunity = resistance of a host to pathogens and their toxic effects Immune response = collective and coordinated response to the introduction of foreign substances in an individual mediated by the cells and molecules of the immune system Laboratory Training for FieldEEpidemiologists P I D E M I C A L E R T A N D R E S P O N S E  Role of the immune system Defense against microbes Defense against the growth of tumor cells kills the growth of tumor cells Homeostasis destruction of abnormal or dead cells (e.g. dead red or white blood cells, antigen-antibody complex) Laboratory Training for FieldEEpidemiologists P I D E M I C A L E R T A N D R E S P O N S E  Immune System 1. Organs 2. Cells 3. Molecules Laboratory Training for FieldEEpidemiologists P I D E M I C A L E R T A N D R E S P O N S E  Immune System: (1) organs Tonsils and adenoids Thymus Lymph nodes Spleen Payer’s patches Appendix Lymphatic vessels Bone marrow Laboratory Training for FieldEEpidemiologists P I D E M I C A L E R T A N D R E S P O N S E  Immune system: (2) cells Lymphocytes T-lymphocytes B-Lymphocytes, plasma cells natural killer lymphocytes Monocytes, Macrophage Granulocytes neutrophils eosinophils basophils Laboratory Training for FieldEEpidemiologists P I D E M I C A L E R T A N D R E S P O N S E  Immune system: (3) molecules Antibodies Complement Cytokines Interleukines Interferons Laboratory Training for FieldEEpidemiologists P I D E M I C A L E R T A N D R E S P O N S E  Two types of immunity 1. Innate (non-adaptive) first line of immune response relies on mechanisms that exist before infection 2. Acquired (adaptive) Second line of response (if innate fails) relies on mechanisms that adapt after infection handled by T- and B- lymphocytes one cell determines one antigenic determinant Laboratory Training for FieldEEpidemiologists P I D E M I C A L E R T A N D R E S P O N S E  Innate immunity Based on genetic make-up Relies on already formed components Rapid response: within minutes of infection Not specific same molecules / cells respond to a range of pathogens Has no memory same response after repeated exposure Does not lead to clonal expansion Laboratory Training for FieldEEpidemiologists P I D E M I C A L E R T A N D R E S P O N S E  Innate immunity: mechanisms Mechanical barriers / surface secretion skin, acidic pH in stomach, cilia Humoral mechanisms lysozymes, basic proteins, complement, interferons Cellular defense mechanisms natural killer cells neutrophils, macrophages,, mast cells, basophils, eosinophils NK Cell Eosinophils Monocyte Neutrophil Basophils & Mast cells Macrophage Laboratory Training for FieldEEpidemiologists P I D E M I C A L E R T A N D R E S P O N S E  Adaptive immunity: second line of response Based upon resistance acquired during life Relies on genetic events and cellular growth Responds more slowly, over few days Is specific each cell responds to a single epitope on an antigen Has anamnestic memory repeated exposure leads to faster, stronger response Leads to clonal expansion Laboratory Training for FieldEEpidemiologists P I D E M I C A L E R T A N D R E S P O N S E  Adaptive Immunity: active and passive Active Immunity Passive Immunity Natural clinical, sub-clinical via breast milk, infection placenta Artificial Vaccination: immune serum, immune cells Live, killed, purified antigen vaccine Laboratory Training for FieldEEpidemiologists P I D E M I C A L E R T A N D R E S P O N S E  Adaptive immunity: mechanisms Cell-mediated immune response (CMIR) T-lymphocytes eliminate intracellular microbes that survive within phagocytes or other infected cells Humoral immune response (HIR) B-lymphocytes mediated by antibodies eliminate extra-cellular microbes and their toxins Plasma cell (Derived from B- lymphocyte, produces antibodies) Laboratory Training for FieldEEpidemiologists P I D E M I C A L E R T A N D R E S P O N S E  Cell-mediated immune response 1. T-cell recognizes peptide antigen on macrophage in association with major histo-compatibility complex (MHC) class identifies molecules on cell surfaces helps body distinguish self from non-self 2. T-cell goes into effectors cells stage that is able to kill infected cells Laboratory Training for FieldEEpidemiologists P I D E M I C A L E R T A N D R E S P O N S E  T lymphocytes 2 types helper T- lymphocytes (CD4+) CD4+ T cells activate phagocytes to kill microbes cytolytic T-lymphocyte (CD8+) CD8+ T cells destroy infected cells containing microbes or microbial proteins Laboratory Training for FieldEEpidemiologists P I D E M I C A L E R T A N D R E S P O N S E  Cell mediated immune response Primary response production of specific clones of effector T cells and memory clones develops in several days does not limit the infection Secondary response more pronounced, faster more effective at limiting the infection Example - cytotoxic reactions against intracellular parasites, delayed hypersensitivity (e.g., Tuberculin test) and allograft rejection Laboratory Training for FieldEEpidemiologists P I D E M I C A L E R T A N D R E S P O N S E  Humoral immune response 1. B lymphocytes recognize specific antigens proliferate and differentiate into antibody-secreting plasma cells 2. Antibodies bind to specific antigens on microbes; destroy microbes via specific mechanisms 3. Some B lymphocytes evolve into the resting state - memory cells Laboratory Training for FieldEEpidemiologists P I D E M I C A L E R T A N D R E S P O N S E  Antibodies (immunoglobulins) Belongto the gamma-globulin fraction of serum proteins Y-shaped or T-shaped polypeptides 2 identical heavy chains 2 identical light chains All immunoglobulins are not antibodies Five kinds of antibodies IgG, IgM, IgA, IgD, IgE Laboratory Training for FieldEEpidemiologists P I D E M I C A L E R T A N D R E S P O N S E  IgG 70-75% of total immunoglobulin Secreted in high quantities in secondary exposures Cross the placenta 4-fold rise or fall indicates active infection Major functions / applications A single positive neutralize microbes and toxins sample indicates past exposure opsonize antigens for phagocytosis activate the complement protect the newborn Laboratory Training for FieldEEpidemiologists P I D E M I C A L E R T A N D R E S P O N S E  IgM Secreted initially during primary infection Cannot cross the placenta Presence in newborn Major functions / applications means infection secreted first during primary Singlepositive sample in exposure serum or CSF indicates recent or active infection activates the complement Used to detect early used as a marker of recent phase of infection infection Laboratory Training for FieldEEpidemiologists P I D E M I C A L E R T A N D R E S P O N S E  IgA Monomeric in serum Dimeric with secretory component in the lumen of the gastro-intestinal tract and in the respiratory tract Major function / application neutralizes microbes and toxins Sero-diagnosis of tuberculosis Synthicial respiratory virus tests Laboratory Training for FieldEEpidemiologists P I D E M I C A L E R T A N D R E S P O N S E  IgD Monomeric Major functions / applications present on the surface of B lymphocytes functions as membrane receptor role unclear has a role in antigen stimulated lymphocyte differentiation Laboratory Training for FieldEEpidemiologists P I D E M I C A L E R T A N D R E S P O N S E  IgE Mediates type I hypersensitivity Monomeric Major functions / applications associated with anaphylaxis plays a role in immunity to Serodiagnosis of infectious and helminthic parasites non infectious allergies (e.g., allergic bronchopulmonary aspergillosis, parasitic diseases) Laboratory Training for FieldEEpidemiologists P I D E M I C A L E R T A N D R E S P O N S E  Sequential IgM-IgG humoral response IgM produced as a first response to many antigens levels remain high transiently IgG produced after IgM higher levels persist in small amounts throughout life produced in large amounts during secondary response persistence of antigen sensitive ‘memory cells’ after primary response Laboratory Training for FieldEEpidemiologists P I D E M I C A L E R T A N D R E S P O N S E  IgM – IgG sequential response Anamnestic response Antibody titer IgG IgM Time First stimulus Second stimulus Laboratory Training for FieldEEpidemiologists P I D E M I C A L E R T A N D R E S P O N S E  Failure of immune response Immune response helps individuals defend against microbes some cancers Immune response can fail hypersensitivity reactions immunodeficiency Laboratory Training for FieldEEpidemiologists P I D E M I C A L E R T A N D R E S P O N S E  Hypersensitivity reactions Cause cell damage through excessive immune response to antigens Hypersensitivity overreaction to infectious agents Allergy overreaction to environmental substances Autoimmunity overreaction to self Laboratory Training for FieldEEpidemiologists P I D E M I C A L E R T A N D R E S P O N S E  Immunodeficiency Loss or inadequate function of various components of the immune system Can occur in any part or state of the immune system physical barrier, phagocytes, B lymphocytes, T lymphocytes, complement, natural killer cells The immuno-compromised host has an impaired function of immune system is at high risk of infection Laboratory Training for FieldEEpidemiologists P I D E M I C A L E R T A N D R E S P O N S E  Immunodeficiency Congenital (primary) immunodeficiency genetic abnormality defect in lymphocyte maturation Acquired (secondary) immunodeficiency results from infections, nutritional deficiencies or treatments AIDS, chronic leukemia Laboratory Training for FieldEEpidemiologists P I D E M I C A L E R T A N D R E S P O N S E  Altered immunity: immuno-compromised Disorder Compromised function Altered anatomic Mucus membrane Reduction in IgA Microbe binding barrier Gastro-intestinal Elevated pH Bacteria killing tract Change in flora Colonization resistance Immune system Innate immunity Reduction of complement Activates phagocytosis Opsonization of bacteria Membrane attack complex Neutropenia Phagocytosis Monocytopenia Bacteria killing Adaptive Reduction of T cells Activation of macrophages immunity Activation of B lymphocytes Hypo-gammaglobulinemia Neutralizes pathogens and toxins, opsonization, complement activation Laboratory Training for FieldEEpidemiologists P I D E M I C A L E R T A N D R E S P O N S E  Summary (1) Innate immunity relies on mechanisms already existing before microbe infects host is the first line of defense has no memory for subsequent exposure relies on non specific mechanisms Laboratory Training for FieldEEpidemiologists P I D E M I C A L E R T A N D R E S P O N S E  Summary (2) Adaptive immunity develops following entry of microbe into the host comes into action after innate immunity fails to get rid of microbe has memory to deal with subsequent exposure happens through specific cells T cells (cell mediated) B cells (antibody mediated) Laboratory Training for FieldEEpidemiologists P I D E M I C A L E R T A N D R E S P O N S E  Summary (3) Primary immune response short lasting smaller in magnitude Secondary immune response longer in duration larger in magnitude develop ‘memory cells’ following primary response Failure of immune response can result in: hypersensitivity immunodeficiency Laboratory Training for FieldEEpidemiologists P I D E M I C A L E R T A N D R E S P O N S E  Investigation strategies and methods Developed by the Department of Epidemic and Pandemic Alert and Response of the World Health Organization with assistance from: European Program for Intervention Epidemiology Training Canadian Field Epidemiology Program Thailand Ministry of Health Institut Pasteur Laboratory Training for FieldEEpidemiologists P I D E M I C A L E R T A N D R E S P O N S E