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 © 2017 Pearson Education, Inc. 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: • Cell-mediated immune responses • Antibody immune responses © 2017 Pearson Education, Inc. Properties of Antigens Molecules the body recognizes as foreign and attack • Recognized by threedimensional regions called epitopes on antigens • Include : • • • • bacterial components proteins of viruses, fungi protozoa • Food and dust can also contain antigenic particles © 2017 Pearson Education, Inc. Elements of Adaptive Immunity • Antigens • Types of Antigens: • Exogenous antigens — include toxins and other components of microbial cell walls, membranes, flagella, and pili (extracellular) • Endogenous antigens — produced by microbes that reproduce inside a body's cells (intracellular) • Autoantigens — derived from normal cellular processes © 2017 Pearson Education, Inc. Elements of Adaptive Immunity • B Lymphocytes (B Cells) and Antibodies • 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 • After activation and differentiation © 2017 Pearson Education, Inc. How do B cells become activated? BCR • Each B lymphocyte has multiple copies of the BCR • Each B cell generates a single BCR • Two variable regions of the BCR form the antigen-binding sites • Each BCR recognizes only one epitope © 2017 Pearson Education, Inc. Basic antibody structure. • • • © 2017 Pearson Education, Inc. are immunoglobulins similar to BCRs Secreted by activated B cells called plasma cells antigen specificity identical to the BCR of the activated B cell Elements of Adaptive Immunity • B Lymphocytes (B Cells) and Antibodies • Antibody Function • Antigen-binding sites are complementary to epitopes • Antibodies function in several ways: • Activation of complement and inflammation • Neutralization • Opsonization • Killing by oxidation • Agglutination • Antibody-dependent cellular cytotoxicity (ADCC) © 2017 Pearson Education, Inc. Five functions of antibodies. © 2017 Pearson Education, Inc. Five functions of antibodies. © 2017 Pearson Education, Inc. Five functions of antibodies. (non-prokaryotic) © 2017 Pearson Education, Inc. Five functions of antibodies. © 2017 Pearson Education, Inc. Five functions of antibodies. © 2017 Pearson Education, Inc. B Lymphocytes (B Cells) and Antibodies • Classes of Antibodies • Threats confronting the immune system are variable • Antibody class involved in the immune response varies • Type of antigen • Portal of entry • Antibody function needed • Five different classes of antibodies © 2017 Pearson Education, Inc. Classes of Antibodies IgM — first antibody produced IgG — most common and longest-lasting antibody IgA — associated with body secretions IgE — involved in response to parasitic infections and allergies • IgD — exact function is not known • • • • © 2017 Pearson Education, Inc. Preparation for an Adaptive Immune Response The Roles of the Major Histocompatibility Complex (MHC) and Antigen-Presenting Cells • Determine compatibility of tissues for tissue grafting • Membrane Proteins • Hold and position antigenic epitopes for presentation to immune cells © 2017 Pearson Education, Inc. The Roles of the Major Histocompatibility Complex (MHC) and Antigen-Presenting Cells • Antigens bind in the antigen-binding groove of MHC molecules • Two classes of MHC proteins: • MHC class I • Present on all cells except red blood cells • Presents intracellular antigens • MHC class II • Present on antigen-presenting cells (APCs) • Macrophages and dendritic cells • Presents Extracellular antigens © 2017 Pearson Education, Inc. The two classes of major histocompatibility complex (MHC) proteins. © 2017 Pearson Education, Inc. The two classes of major histocompatibility complex (MHC) proteins. © 2017 Pearson Education, Inc. T Lymphocytes (T Cells) Specificity of the T Cell Receptor (TCR • TCRs do not recognize epitopes directly • TCRs only bind epitopes associated with an MHC protein • T cells act primarily against cells that harbor intracellular pathogens • Some T cells act against body cells that produce abnormal cellsurface proteins © 2017 Pearson Education, Inc. Elements of Adaptive Immunity • T Lymphocytes (T Cells) • Types of T Lymphocytes • Based on surface glycoproteins and characteristic functions, three types: • Cytotoxic T lymphocyte • Directly kills other cells • MHC I • Helper T lymphocyte • Helps regulate B cells and cytotoxic T cells • Includes type 1 and type 2 helper T cells • MHCII • Regulatory T lymphocyte • Represses adaptive immune responses © 2017 Pearson Education, Inc. Elements of Adaptive Immunity • Immune Response Cytokines • Soluble regulatory proteins that act as intercellular signals • Cytokines secreted by various leukocytes • Cytokine network • Complex web of signals among cells of the immune system © 2017 Pearson Education, Inc. Cell-Mediated Immune Responses • Respond to intracellular pathogens and abnormal body cells • Common intracellular pathogens are viruses • The response is also effective against cancer cells, intracellular protozoa, and intracellular bacteria © 2017 Pearson Education, Inc. Cell-Mediated Immune Responses • Activation of Cytotoxic T Cell Clones and Their Functions • Adaptive immune responses initiated in lymphoid organs • Steps involved in activation of cytotoxic T cells: 1. 2. 3. 4. © 2017 Pearson Education, Inc. Antigen presentation Helper T cell differentiation Clonal expansion Self-stimulation Activation of a clone of cytotoxic T (Tc) cells. Dendritic cell Antigen presentation MHC I CD8 DC MHC II Epitope MHC I Epitope TCR TCR Th cell Tc cell Inactive Tc cell IL-12 Immunological synapse IL-2 receptor (IL-2R) Th differentiation IL-2 Clonal expansion Th1 cell IL-2R IL-2 IL-2R Memory T cell Active Tc cells IL-2 Self-stimulation Active Tc cells IL-2 © 2017 Pearson Education, Inc. Effector function Activation of Cytotoxic T Cell Clones and Their Functions • Perforin-granzyme pathway • Involves synthesis of special killing proteins © 2017 Pearson Education, Inc. Activation of Cytotoxic T Cell Clones and Their Functions • CD95 pathway • Mediated through glycoprotein on body's cells © 2017 Pearson Education, Inc. Inducement of T-Dependent Antibody Immunity with Clonal Selection • T-dependent antibody immunity • Depend on the function of helper T cells • Four steps of this immune response: 1. 2. 3. 4. Antigen presentation for Th activation and cloning Differentiation of helper T cells into Th2 cells Activation of B cells Proliferation of B cells © 2017 Pearson Education, Inc. A T-dependent antibody immune response. © 2017 Pearson Education, Inc. A T cell-dependent antibody immune response. © 2017 Pearson Education, Inc. A T-dependent antibody immune response. © 2017 Pearson Education, Inc. (prevents reinfection) How do Immune Cells Communicate? Immune Response Cytokines • Soluble regulatory proteins that act as intercellular signals • Cytokines secreted by various leukocytes • Cytokine network • Complex web of signals among cells of the immune system © 2017 Pearson Education, Inc. Elements of Adaptive Immunity • Immune Response 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 © 2017 Pearson Education, Inc. Selected Immune Response Cytokines © 2017 Pearson Education, Inc. Antibody mediated testing How can we use what we know about antibodies to diagnose or prevent illness? © 2017 Pearson Education, Inc. The indirect fluorescent antibody test. Labeled Antibody Tests Fluorescent Antibody Tests Use fluorescent dyes as labels © 2017 Pearson Education, Inc. Serological Tests That Use Antigens and Corresponding Antibodies ELISAs • enzyme-linked immunosorbent assay (ELISA) • Uses an enzyme as the label • Reaction of enzyme with its substrate produces a colored product indicating a positive test • Commonly used to detect the presence of serum antibodies Has a person Encountered an Antigen? © 2017 Pearson Education, Inc. Enzyme-linked immunosorbent assay (ELISA), also known as enzyme immunoassay (EIA). © 2017 Pearson Education, Inc. ELISAs Advantages of the ELISA: • • • • • • Can detect either antibody or antigen Sensitive Can quantify amounts of antigen or antibody Easy to perform and can test many samples quickly Easy to automate Plates coated with antigen can be stored for later testing © 2017 Pearson Education, Inc. Enzyme-linked immunosorbent assay (ELISA), also known as enzyme immunoassay (EIA). © 2017 Pearson Education, Inc. Antibody sandwich ELISA: is there antigen present? • Modification of the ELISA technique • Antigen being tested for is "sandwiched" between two antibody molecule Is Antigen Present? © 2017 Pearson Education, Inc.
