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Adaptive Immune System Chapter 16 Innate vs. adaptive • Innate – Nonspecific response • A fever is a fever whether triggered by a cold virus or Ebola – Always ready and fast acting • Born with these systems • Adaptive – Specific immune response to an antigen • If you have a cold virus antibodies are produced specifically for that virus – Slower – Not born with an adaptive system • Antibodies can be transferred through breast milk 5 attributes of the adaptive immune system 1. 2. 3. 4. 5. Specificity – Any adaptive response acts against only 1 particular molecule shape (antigen) and not others Inducibility – Cells of adaptive immunity are activated in response to the specific antigen Clonality – Once induced cells proliferate to form many generations of identical cells Unresponsive to self – Adaptive immune cells don’t act on normal body cells Memory – Adaptive cells form memory which accounts for a fast secondary response Where does the Adaptive Immune response take place? – The Tissues and Organs of the Lymphatic System • Act as a surveillance system that screens the tissues of the body for foreign antigens • Composed of lymphatic vessels and lymphatic cells, tissues, and organs Antigens • Antigen: a substance that causes the body to stimulate an adaptive immune response • Include various bacterial components as well as proteins of viruses, fungi, and protozoa • Food and dust can also contain antigenic particles Extracellular microbes Types of antigens • Exogenous • Extracellular Exogenous antigens – Toxins and other secretions – Components of cell walls, membranes, flagella • Endogenous • Intracellular – Endogenous antigens are not accessible to immune cells – Immune cells will respond if the endogenous antigen is incorporated into the bodies cells cytoplasmic membranes (external display) • Autoantigens – Self antigens – Derived from normal cell processes Endogenous antigens Intracellular virus Virally infected cell Autoantigens (normal cell antigens) Normal (uninfected) cell Major Histocompatibility Complex (MHC) – MHC proteins hold and position antigens for presentation – Two classes of MHC proteins – MHC class I- Found on every nucleated cell except RBCs – MHC class II- Found only on B cells and antigen presenting cells (APC) (macrophages and dendritic cells) Major Histocompatibility Complex (MHC) • Antigens bind to MHC molecules Antigen-binding grooves Cytoplasmic membrane Class I MHC on every nucleated cell Class II MHC on B cell or other antigen-presenting cell (APC) Adaptive immune cells • T and B cells develop from stem cells in red bone Stem cells develop in bone marrow marrow Red bone marrow of adults Thymus Differentiate to B cells in adult red bone marrow Differentiate to T cells in thymus Migrate to lymphoid tissue such as spleen, but especially lymph nodes B Cells • Found primarily in the spleen and lymph nodes – Small percentage of B cells circulate in the blood • Respond to extracellular antigens (exogenous antigens) • Major function – differentiation into plasma cells for the eventual secretion of antibodies – development of memory B cells (involved in a secondary response toward the same antigen) B Cells • B cells have immunoglobulin's on surface of cell – Called B cell receptors (BCRs) • Each B lymphocyte has multiple copies of the same B cell receptor • Each B cell generates a single BCR – ~500,000 identical copies per cell – Billions of different B cells each with a unique BCR in a human Figure 16.4 B cell receptor (BCR) Antigen Antigenbinding sites Variable region Cytoplasmic membrane of B lymphocyte B cell receptor (BCR) Cytoplasm Antibodies • Globular proteins called immunoglobulin's • Secreted by plasma cells • Antibodies interact with antigens Antibodies interacting with Antigen Antibody A antigenic determinants on antigen Antigens: components of cell wall Binding sites Bacterial cell Antibody B Antibodies • Classes of antibodies – IgM–first antibody produced – IgG–most common (80% of serum antibodies) and longest-lasting antibody – IgA– associated with body secretions, provides nursing newborns some protection against foreign antigens, newborn receives antibodies against antigens that have infected their mothers – IgE–involved in response to parasitic infections and allergies – IgD–exact function is not known Outcomes of Antigen–Antibody Binding • • • • Agglutination Opsonization Activation of complement Antibody-dependent cell-mediated cytotoxicity (ADCC) • Neutralization The results of antigen–antibody binding. Agglutination Reduces number of infectious units to be dealt with PROCTECTIVE MECHANISM OF BINDING Activation of complement ANTIBODIES Causes inflammation and TO ANTIGENS cell lysis Complement Bacteria Bacterium Lysis Antibody-dependent cell-mediated cytotoxicity Opsonization Coating antigen with antibody enhances phagocytosis Phagocyte Antibodies attached to target cell cause destruction by macrophages, eosinophils, and NK cells Eosinophil Epitopes Neutralization Blocks adhesion of bacteria and viruses to mucosa Virus Bacterium Large target cell (parasite) Toxin Blocks attachment of toxin Perforin and lytic enzymes T Cells • Have T cell receptors (TCRs) on their cytoplasmic membrane • TCRs do not recognize antigens directly • TCRs only bind antigen associated with a MHC protein • Have either CD 4 or CD 8 protein – T Helper lymphocyte • Helps regulate the activities of B cells and cytotoxic T cells – T helper cells require antigen-presenting cells (APCs) with MHC class II • CD 4 T Cells • Cytotoxic T lymphocytes (Tc or CTL) • Have TCRs and CD8 which recognize Endogenous antigen packaged with MHC class I protein on virally or intracellular pathogen infected cells. • Must be activated • Produce perforins and granzyme – Directly kills infected cells • Tc cells require antigen-presenting cells with MHC class I 2 types of adaptive immune responses • Two types of adaptive immune responses 1. Humoral immune responses- extracellular • Antibody immunity – 2 types 1. T-dependent 2. T-independent 2. Cell-mediated immune responses- intracellular pathogens (viruses replicating inside a cell) • No antibodies are involved Humoral Response • Components involved in Humoral immunity: – Extra cellular antigen – B cells • BCRs – T helper cells (T-dependent humoral immunity only) • CD4 – helps Th cell to recognize MHC II – MHC class II proteins – Exogenous antigen processing – Cytokines (chemical signalling) Antigen presenting cells (APC) – Use Exogenous antigen processing – Phagocytosis and Digestion antigen – Display antigen fragments on APC surface with MHC 1.Macrophages 2.Dendritic cells- “scouts” very important! • Found under surface of skin and mucous membranes • After acquiring antigen they will migrate to lymph nodes to interact with B and T cells 3.B cells A dendritic cell. Antigen Processing – Exogenous Antigen processing • Antigen presenting cells internalize the antigen and digest the in the phagolysosome • A vesicle containing MHC II fuses with the phagolysosome and the antigens can bind to its complementary MHC II molecule Role of CD4 • CD4 protein on T helper recognizes MHC class II • T helpers become activated when antigen is presented on a MHC II and matches its TCR Humoral Immune Response • Two types – T-independent humoral immunity – T-dependent humoral immunity T-independent humoral immunity • Does not need assistance from helper T cells • When a molecule with multiple repeating antigen (such as a polysaccharide) cross-links the BCRs on a B cell – 1. The B cell is activated – 2. undergoes clonal expansion – 3. the clones become plasma cells which secrete antibodies T-independent humoral immunity Polysaccharide (T-independent antigen) Epitopes B cell receptors T-independent humoral response worksheet T-dependent humoral immunity The process • T-dependent – Requires T helper cells – Antigen is presented with MHC II to TH cell – TH cell produces cytokines that activate the B cell – Once B cell is activated the B cell undergoes clonal expansion – B cells differentiate into: • Antibody-producing plasma cells • Memory cells Clonal selection and differentiation of B cells. Stem cell Stem cells differentiate into mature B cells, each bearing surface immunoglobulins against a specific antigen. Antigen B cell III complexes with its specific antigen and proliferates. B cells I II III IV Memory cells Some B cells proliferate into longlived memory cells, which at a later date can be stimulated to become antibody-producing plasma cells. See Figure 17.17. Other B cells proliferate into antibody-producing plasma cells. Plasma cells Plasma cells secrete antibodies into circulation. Antigens in circulation now attached to circulating antibodies Cardiovascular system T-dependent humoral response worksheet Humoral Immune Responses • Memory B Cells and the Establishment of Immunological Memory – Produced by B cell proliferation but do not secrete antibodies – Have BCRs complementary to the antigenic determinant that triggered their production – Long-lived cells that persist in the lymphoid tissue – Initiate antibody production if antigen is encountered again Figure 16.19 The production of primary and secondary humoral immune responses--overview Cell mediated response • The Players – Intracellular antigen (virally infected cells) – T cytotoxic cells (Tc) – Cytotoxic T lymphocytes (CTLs) – CD8 – T helper cells – APCs • Macrophages • Dendritic cells – MHC class I Antigen Processing • Endogenous – from pathogens living within a cell the antigen is broken down and packaged inside the cell with MHC I and displayed on the cell surface Processed antigen presented with MHC class I Virus Processed antigen Virus-infected cell MHC class I Virus-infected cell (example of endogenous antigen) Virus-infected cell Cell-Mediated Immune Responses • See worksheet Figure 16.15b A cell-mediated immune response: perforin-granzyme cytotoxic pathway Tc cell Perforin Granzyme Perforin complex (pore) Granzymes activate apoptotic enzymes Inactive apoptotic enzymes Active apoptotic enzymes induce apoptosis Virally infected cell Apoptosis. Natural Killer (NK) Cells • Granular leukocytes destroy cells that don’t express MHC I • Kill virus-infected and tumor cells • Attack parasites Types of Acquired Immunity • Specific immunity acquired during an individual’s life – Naturally acquired • Response against antigens encountered in daily life – Distinguished as either active or passive • Active- normal exposure and response to pathogen • Passive immunity – Receive antibodies from another individual » Newborns respond slowly to antigen » IgG crosses the placenta providing protection – IgA in breast milk- – Artificially acquired • Active-Response to antigens introduced via a vaccine • Passive- administration of antisera or antitoxins