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MICROBIOLOGY WITH DISEASES BY BODY SYSTEM SECOND EDITION Chapter 16 Adaptive Immunity Lecture prepared by Mindy Miller-Kittrell, University of Tennessee, Knoxville Copyright © 2009 Pearson Education Inc., publishing as Pearson Benjamin Cummings Overview of Adaptive Immunity • Adaptive immunity is the body’s ability to recognize and defend itself against distinct invaders and their products • Five attributes of adaptive immunity – Specificity – Inducibility – Clonality – Unresponsiveness to self – Memory Copyright © 2009 Pearson Education Inc., publishing as Pearson Benjamin Cummings Overview of Adaptive Immunity • Involves activity of lymphocytes • Two main types of lymphocytes – B lymphocytes (B cells) – Mature in the bone marrow – T lymphocytes (T cells) – Mature in the thymus • Two types of adaptive immune responses – Humoral immune responses – Cell-mediated immune responses Copyright © 2009 Pearson Education Inc., publishing as Pearson Benjamin Cummings Overview of Adaptive Immunity [INSERT FIGURE 16.1] Copyright © 2009 Pearson Education Inc., publishing as Pearson Benjamin Cummings Overview of Adaptive Immunity Animation: Host Defenses: Cell-Medicated Immunity: Overview Animation: Host Defenses: Humoral Immunity: Overview Copyright © 2009 Pearson Education Inc., publishing as Pearson Benjamin Cummings Elements of Adaptive Immunity • The Tissues and Organs of the Lymphatic System – Screen the tissues of the body for foreign antigens – Composed of lymphatic vessels and lymphatic cells, tissues, and organs Copyright © 2009 Pearson Education Inc., publishing as Pearson Benjamin Cummings Elements of Adaptive Immunity • The Tissues and Organs of the Lymphatic System – Lymphatic vessels and the flow of lymph – Form a one-way system that conducts lymph from local tissues and returns it to the circulatory system – Lymph is a liquid with similar composition to blood plasma, which arises from fluid leaked from blood vessels into surrounding tissues Copyright © 2009 Pearson Education Inc., publishing as Pearson Benjamin Cummings Elements of Adaptive Immunity [INSERT FIGURE 16.2] Copyright © 2009 Pearson Education Inc., publishing as Pearson Benjamin Cummings Elements of Adaptive Immunity • The Tissues and Organs of the Lymphatic System – Lymphoid organs – Primary lymphoid organs – Red bone marrow – Thymus – Secondary lymphoid organs – Lymph nodes – Spleen – Tonsils – Mucosa-associated lymphatic tissue (MALT) Copyright © 2009 Pearson Education Inc., publishing as Pearson Benjamin Cummings Elements of Adaptive Immunity [INSERT FIGURE 16.3] Copyright © 2009 Pearson Education Inc., publishing as Pearson Benjamin Cummings Elements of Adaptive Immunity • Antigens – Properties of antigens – Molecules the body recognizes as foreign and worthy of attack – Body recognizes antigens by three-dimensional regions called epitopes – Include components of bacterial cell walls, capsules, pili, and flagella, as well as proteins of viruses, fungi, and protozoa – Food and dust can also contain antigenic particles Copyright © 2009 Pearson Education Inc., publishing as Pearson Benjamin Cummings Elements of Adaptive Immunity [INSERT FIGURE 16.4a] Copyright © 2009 Pearson Education Inc., publishing as Pearson Benjamin Cummings Elements of Adaptive Immunity [INSERT FIGURE 16.4b-d] Copyright © 2009 Pearson Education Inc., publishing as Pearson Benjamin Cummings Elements of Adaptive Immunity • B Lymphocytes (B Cells) and Antibodies – Arise and mature in the red bone marrow – Found primarily in the spleen, lymph nodes, and MALT – Small percentage of B cells circulate in the blood – Major function is the secretion of antibodies Copyright © 2009 Pearson Education Inc., publishing as Pearson Benjamin Cummings Elements of Adaptive Immunity • B Lymphocytes (B Cells) and Antibodies – Specificity of the B cell receptor (BCR) – Each B lymphocyte has multiple copies of a single type of protein called the B cell receptor – Each B cell generates a single BCR – The two variable regions of the BCR form the antigen-binding sites – Each BCR recognizes only one epitope – The entire repertoire of an individual’s BCRs is capable of recognizing millions of different epitopes Copyright © 2009 Pearson Education Inc., publishing as Pearson Benjamin Cummings Elements of Adaptive Immunity [INSERT FIGURE 16.5] Copyright © 2009 Pearson Education Inc., publishing as Pearson Benjamin Cummings Elements of Adaptive Immunity • B Lymphocytes (B Cells) and Antibodies – Specificity and antibody structure – Antibodies are immunoglobulins similar to BCRs – Secreted by activated B cells called plasma cells – Have identical antigen-binding sites and antigen specificity as the BCR of the activated B cell Copyright © 2009 Pearson Education Inc., publishing as Pearson Benjamin Cummings Elements of Adaptive Immunity [INSERT FIGURE 16.6] Copyright © 2009 Pearson Education Inc., publishing as Pearson Benjamin Cummings Elements of Adaptive Immunity • B Lymphocytes (B Cells) and Antibodies – Classes of antibodies – Threats confronting the immune system are variable – The class involved in the immune response depends on the type of foreign antigen, the portal of entry, and the antibody function needed – Five different classes of antibodies Copyright © 2009 Pearson Education Inc., publishing as Pearson Benjamin Cummings Elements of Adaptive Immunity [INSERT TABLE 16.1] Copyright © 2009 Pearson Education Inc., publishing as Pearson Benjamin Cummings Elements of Adaptive Immunity • B Lymphocytes (B Cells) and Antibodies • Antibody function – Antigen-binding sites are complementary to epitopes – Due to the close match can form strong, noncovalent interactions – Hydrogen bonds and other attractions may also be involved – Antibodies function in several ways – Activation of complement and inflammation – Neutralization – Opsonization – Killing by oxidation – Agglutination – Antibody-dependent cellular cytotoxicity (ADCC) Copyright © 2009 Pearson Education Inc., publishing as Pearson Benjamin Cummings Elements of Adaptive Immunity [INSERT FIGURE 16.7] Copyright © 2009 Pearson Education Inc., publishing as Pearson Benjamin Cummings Elements of Adaptive Immunity Animation: Host Defenses: Humoral Immunity: Antibody Function Copyright © 2009 Pearson Education Inc., publishing as Pearson Benjamin Cummings Elements of Adaptive Immunity • T Lymphocytes (T Cells) – Produced in the red bone marrow and mature under the influence of the thymus – Circulate in the lymph and blood and migrate to the lymph nodes, spleen, and Peyer’s patches – Antigen-binding sites are complementary to epitopes – T cells have T cell receptors (TCRs) on their cytoplasmic membrane Copyright © 2009 Pearson Education Inc., publishing as Pearson Benjamin Cummings Elements of Adaptive Immunity • T Lymphocytes – Specificity of the T cell receptor (TCR) – TCRs do not recognize epitopes directly – TCRs only bind epitopes associated with a MHC protein – Act primarily against body cells that harbor intracellular pathogens Copyright © 2009 Pearson Education Inc., publishing as Pearson Benjamin Cummings Elements of Adaptive Immunity [INSERT FIGURE 16.8] Copyright © 2009 Pearson Education Inc., publishing as Pearson Benjamin Cummings Elements of Adaptive Immunity • T Lymphocytes – Types of T lymphocytes – Based on surface glycoproteins and characteristic functions – Three types – Cytotoxic T lymphocyte – directly kills other cells – Helper T lymphocyte – functions to “help” regulate the activities of B cells and cytotoxic T cells – Regulatory T lymphocyte – represses adaptive immune responses Copyright © 2009 Pearson Education Inc., publishing as Pearson Benjamin Cummings Elements of Adaptive Immunity Animation: Host Defenses: Cell-Mediated Immunity: Cytotoxic T Cells Copyright © 2009 Pearson Education Inc., publishing as Pearson Benjamin Cummings Elements of Adaptive Immunity Animation: Host Defenses: Cell-Mediated Immunity: Helper T Cells Copyright © 2009 Pearson Education Inc., publishing as Pearson Benjamin Cummings Elements of Adaptive Immunity [INSERT TABLE 16.2] Copyright © 2009 Pearson Education Inc., publishing as Pearson Benjamin Cummings Elements of Adaptive Immunity • Clonal Deletion – Vital that immune responses not be directed against autoantigens – Body eliminates self-reactive lymphocytes via clonal deletion – Lymphocytes that react to autoantigens undergo apoptosis Copyright © 2009 Pearson Education Inc., publishing as Pearson Benjamin Cummings Elements of Adaptive Immunity [INSERT FIGURE 16.9] Copyright © 2009 Pearson Education Inc., publishing as Pearson Benjamin Cummings Elements of Adaptive Immunity [INSERT FIGURE 16.10] Copyright © 2009 Pearson Education Inc., publishing as Pearson Benjamin Cummings Elements of Adaptive Immunity • Immune System Cytokines – Soluble regulatory proteins that act as intercellular signals when released from certain body cells – Immune system cytokines secreted by various leukocytes – The complex web of signals among all the cell types of the immune system is referred to as the cytokine network Copyright © 2009 Pearson Education Inc., publishing as Pearson Benjamin Cummings Elements of Adaptive Immunity • Immune System Cytokines – Interleukins (ILs) – signal among leukocytes – Interferons (IFNs) – antiviral proteins that may act as cytokines – Growth factors – proteins that stimulate stem cells to divide – Tumor necrosis factor (TNF) – Secreted by macrophages and T cells to kill tumor cells and regulate immune responses and inflammation – Chemokines – chemotactic cytokines that signal leukocytes to move Copyright © 2009 Pearson Education Inc., publishing as Pearson Benjamin Cummings Preparation for an Adaptive Immune Response • The Roles of the Major Histocompatibility Complex – Group of antigens first identified in graft patients – Important in determining the compatibility of tissues in successful grafting – Major histocompatibility antigens are glycoproteins found in the membranes of most cells of vertebrate animals – Function to hold and position antigenic determinants for presentation to T cells Copyright © 2009 Pearson Education Inc., publishing as Pearson Benjamin Cummings Preparation for an Adaptive Immune Response • The Roles of the Major Histocompatibility Complex – Antigens bind in the antigen-binding groove of MHC molecules – Two classes of MHC proteins – MHC class I – MHC class II Copyright © 2009 Pearson Education Inc., publishing as Pearson Benjamin Cummings Preparation for an Adaptive Immune Response [INSERT FIGURE 16.11] Copyright © 2009 Pearson Education Inc., publishing as Pearson Benjamin Cummings Preparation for an Adaptive Immune Response [INSERT FIGURE 16.12] Copyright © 2009 Pearson Education Inc., publishing as Pearson Benjamin Cummings Preparation for an Adaptive Immune Response • Antigen Processing – Antigens must be processed for MHC proteins to display epitopes – Antigen processing occurs by different processes for endogenous and exogenous antigens Copyright © 2009 Pearson Education Inc., publishing as Pearson Benjamin Cummings Preparation for an Adaptive Immune Response Animation: Host Defenses: Antigen Processing and Presentation: Overview Copyright © 2009 Pearson Education Inc., publishing as Pearson Benjamin Cummings Preparation for an Adaptive Immune Response Copyright © 2009 Pearson Education Inc., publishing as Pearson Benjamin Cummings Preparation for an Adaptive Immune Response Copyright © 2009 Pearson Education Inc., publishing as Pearson Benjamin Cummings Preparation for an Adaptive Immune Response Animation: Host Defenses: Antigen Processing and Presentation: Steps Copyright © 2009 Pearson Education Inc., publishing as Pearson Benjamin Cummings Preparation for an Adaptive Immune Response Animation: Host Defenses: Antigen Processing and Presentation: MHC Copyright © 2009 Pearson Education Inc., publishing as Pearson Benjamin Cummings Cell-Mediated Immune Responses • Responds to intracellular pathogens and abnormal body cells • The most common intracellular pathogens are viruses but the response is also effective against cancer cells, intracellular protozoa, and intracellular bacteria Copyright © 2009 Pearson Education Inc., publishing as Pearson Benjamin Cummings Cell-Mediated Immune Responses • Activation of T Cell Clones and Their Functions – Steps involved in activation of cytotoxic T cells – Antigen presentation – Helper T cell differentiation – Clonal expansion – Self-stimulation Copyright © 2009 Pearson Education Inc., publishing as Pearson Benjamin Cummings Cell-Mediated Immune Responses [INSERT FIGURE 16.14] Copyright © 2009 Pearson Education Inc., publishing as Pearson Benjamin Cummings Cell-Mediated Immune Responses Copyright © 2009 Pearson Education Inc., publishing as Pearson Benjamin Cummings Cell-Mediated Immune Responses Animation: Host Defenses: Cell-Mediated Immunity: Cytotoxic T Cells Copyright © 2009 Pearson Education Inc., publishing as Pearson Benjamin Cummings Cell-Mediated Immune Responses Copyright © 2009 Pearson Education Inc., publishing as Pearson Benjamin Cummings Cell-Mediated Immune Responses • Memory T Cells – Some activated T cells become memory T cells – Persist for months or years in lymphoid tissues – Become functional immediately upon subsequent contacts with epitope specific to its TCR Copyright © 2009 Pearson Education Inc., publishing as Pearson Benjamin Cummings Cell-Mediated Immune Responses • T Cell Regulation – Careful regulation of cell-mediated immune response to prevent T cells from responding to autoantigens – T cells require additional signals from an antigen-presenting cell – Interaction of the T cell and antigen-presenting cell at an immunological synapse stimulates the T cell to respond to the antigen Copyright © 2009 Pearson Education Inc., publishing as Pearson Benjamin Cummings Humoral Immune Responses • Body mounts humoral immune responses against exogenous pathogens • Activates only in response to specific pathogens Copyright © 2009 Pearson Education Inc., publishing as Pearson Benjamin Cummings Humoral Immune Responses [INSERT FIGURE 16.16] Copyright © 2009 Pearson Education Inc., publishing as Pearson Benjamin Cummings Humoral Immune Responses [INSERT FIGURE 16.17] Copyright © 2009 Pearson Education Inc., publishing as Pearson Benjamin Cummings Humoral Immune Responses [INSERT FIGURE 16.18] Copyright © 2009 Pearson Education Inc., publishing as Pearson Benjamin Cummings Humoral Immune Responses Animation: Host Defenses: Humoral Immunity: Clonal Selection and Expansion Copyright © 2009 Pearson Education Inc., publishing as Pearson Benjamin Cummings Humoral Immune Responses • Inducement of T-Dependent Humoral Immunity – Plasma cells – Make up the majority of cells produced during B cell proliferation – Each plasma cell secretes only antibody molecules complementary to the specific antigen – Are short-lived cells that die within a few days of activation, though their antibodies and progeny can persist Copyright © 2009 Pearson Education Inc., publishing as Pearson Benjamin Cummings Humoral Immune Responses • Memory B Cells and the Establishment of Immunological Memory – Cells produced by B cell proliferation that do not secrete antibodies – Cells that have BCRs complementary to the specific antigenic determinant that triggered their production – Long-lived cells that persist in the lymphoid tissue – Available to initiate antibody production if the same antigen is encountered again Copyright © 2009 Pearson Education Inc., publishing as Pearson Benjamin Cummings Humoral Immune Responses Copyright © 2009 Pearson Education Inc., publishing as Pearson Benjamin Cummings Humoral Immune Responses Animation: Host Defenses: Humoral Immunity: Primary Immune Response Copyright © 2009 Pearson Education Inc., publishing as Pearson Benjamin Cummings Humoral Immune Responses Animation: Host Defenses: Humoral Immunity: Secondary Immune Response Copyright © 2009 Pearson Education Inc., publishing as Pearson Benjamin Cummings Humoral Immune Responses Animation: Host Defenses: The Big Picture Copyright © 2009 Pearson Education Inc., publishing as Pearson Benjamin Cummings Types of Acquired Immunity • Specific immunity acquired during an individuals life • Two types – Naturally acquired – immune response against antigens encountered in daily life – Artificially acquired – response to antigens introduced via a vaccine • Further distinguished as either active or passive – Active – active response to antigens via humoral or cell-mediated responses – Passive – passively receive antibodies from another individual Copyright © 2009 Pearson Education Inc., publishing as Pearson Benjamin Cummings Types of Acquired Immunity [INSERT TABLE 16.3] Copyright © 2009 Pearson Education Inc., publishing as Pearson Benjamin Cummings