30 Jun Fill the leukocyte table, biology assignment help
Cell Micro Appear Blood or Tissue Main Target Granules/chemical Phagocytes Antigen presenting Receptors/cell surface marker Specific features PowerPoint® Lecture Presentations prepared by Mindy Miller-Kittrell, North Carolina State University CHAPTER 16 Adaptive Immunity © 2015 Pearson Education, Inc. Immunology Fantastic Bioflix video traces a microbe and how the immune System handles it More great videos – you’re going to need these! Host Defenses: The Big Picture Cell-Mediated Immunity: Overview Humoral Immunity: Overview • Don’t forget to use the cells in this set of slides to fill out your leukocyte table © 2015 Pearson Education, Inc. A great summary slide © 2015 Pearson Education, Inc. http://thelifeofapremed.tumblr.com/post/56690250816/le ukocytes-macrophages-neutrophils-mast-cells 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 © 2015 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 © 2015 Pearson Education, Inc. Figure 16.1 Lymphocytes play a central role in adaptive immunity. Lymphocyte © 2015 Pearson Education, Inc. Red blood cell Elements of Adaptive Immunity • The Tissues and Organs of the Lymphatic System • Composed of lymphatic vessels and lymphatic cells, tissues, and organs • Screen the tissues of the body for foreign antigens © 2015 Pearson Education, Inc. Elements of Adaptive Immunity • The Tissues and Organs of the Lymphatic System • The lymphatic vessels and the flow of lymph • Lymphatic vessels • One-way system that conducts lymph from tissues and returns it to the circulatory system • Lymph • Liquid with composition similar to blood plasma • Arises from fluid leaked from blood vessels into surrounding tissues © 2015 Pearson Education, Inc. Figure 16.2 The lymphatic system. From heart Blood capillary Tonsils Tissue cell Cervical lymph node Lymphatic ducts Intercellula r fluid Thymus gland Lymph to heart via lymphatic vessels Axillary lymph node Heart Breast lymphatics Spleen Gap in wall Valve Abdominal lymph node To heart Intestines Lymphatic capillary Peyer’s patches in intestinal wall Appendix Red bone marrow Afferent lymphatic vessel Inguinal lymph node Medulla Lymphatic vessel Cortex Vein Artery Valve (prevents backflow) Efferent lymphatic vessel Lymphatic nodule Capsule Primary follicle © 2015 Pearson Education, Inc. Part of mucosaassociated lymphoid tissue (MALT) 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 lymphoid tissue (MALT) © 2015 Pearson Education, Inc. Elements of Adaptive Immunity • Antigens • Properties of antigens • Molecules that the body recognizes as foreign and worthy of attack • Recognized by three-dimensional regions called epitopes on antigens • Large foreign macromolecules make the best antigens • Include various bacterial components as well as proteins of viruses, fungi, and protozoa • Food and dust can also contain antigenic particles © 2015 Pearson Education, Inc. Figure 16.3a Antigens, molecules that provoke a specific immune response. Epitopes (antigenic determinants) Cytoplasmic membrane Nucleus Antigen Epitopes (antigenic determinants) © 2015 Pearson Education, Inc. Cytoplasm Figure 16.3b-d Antigens, molecules that provoke a specific immune response. Autoantigens (normal cell antigens) Endogenous antigens Extracellular microbes Intracellular virus Exogenous antigens Exogenous antigens © 2015 Pearson Education, Inc. Normal (uninfected) cell Virally infected cell Endogenous antigens Autoantigens Elements of Adaptive Immunity • T Lymphocytes (T Cells) and Preparation for an Adaptive Immune Response • T cells act primarily against cells that harbor intracellular pathogens • Some T cells act against body cells that produce abnormal cell-surface proteins • Circulate in the lymph and blood • Migrate to the lymph nodes, spleen, and Peyer’s patches • Have T cell receptors (TCRs) on their cytoplasmic membrane © 2015 Pearson Education, Inc. Elements of Adaptive Immunity • T Lymphocytes (T Cells) and Preparation for an Adaptive Immune Response • Specificity of the T cell receptor (TCR) • Each cell’s TCR has a specific antigen-binding site • TCRs do not recognize epitopes directly • TCRs bind only epitopes associated with an MHC protein © 2015 Pearson Education, Inc. Figure 16.4 A T cell receptor (TCR). Antigen-binding site Carbohydrate Variable regions Constant regions Cytoplasmic membrane of T cell T cell receptor (TCR) © 2015 Pearson Education, Inc. Cytoplasm Preparation for an Adaptive Immune Response • T Lymphocytes (T Cells) and Preparation for an Adaptive Immune Response • The Roles of the Major Histocompatibility Complex and Antigen-Presenting Cells • Group of antigens first identified in graft patients • Important in determining compatibility of tissues for tissue grafting • Major histocompatibility antigens are glycoproteins found in the membranes of most cells of vertebrate animals • Hold and position antigenic determinants for presentation to T cells © 2015 Pearson Education, Inc. Preparation for an Adaptive Immune Response • T Lymphocytes (T Cells) and Preparation for an Adaptive Immune Response • The Roles of the Major Histocompatibility Complex 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 • MHC class II • Present on antigen-presenting cells (APCs) • Include B cells, macrophages, and dendritic cells © 2015 Pearson Education, Inc. Figure 16.5 The two classes of major histocompatibility complex (MHC) proteins. Antigen-binding sites (grooves) Cytoplasmic membrane Class I MHC on every nucleated cell © 2015 Pearson Education, Inc. Class II MHC on B cell or other antigen-presenting cell (APC) Cytoplasm Figure 16.6 Dendritic cells. Dendrites © 2015 Pearson Education, Inc. Preparation for an Adaptive Immune Response • T Lymphocytes (T Cells) and Preparation for an Adaptive Immune Response • Antigen processing • Antigens processed for MHC proteins to display epitopes • Different processes for endogenous and exogenous antigens © 2015 Pearson Education, Inc. Antigen Processing and Presentation: Overview video © 2015 Pearson Education, Inc. Figure 16.7 The processing of T-dependent endogenous antigens. The cell becomes infected by the intracellular pathogen 1 Polypeptide is catabolized. MHC I protein in membrane of endoplasmic reticulum Epitopes MHC I protein– epitope complex Lumen of endoplasmic reticulum 2 Epitopes are loaded onto complementary MHC I 3 Golgi bodies package MHC I protein–epitope complexes into vesicles. proteins in the ER. 4 Vesicles fuse with cytoplasmic membrane. MHC I protein– epitope complexes on cell surface Cytoplasmic membrane 5 MHC I protein–epitope complexes are displayed on cytoplasmic membranes of all nucleated cells. © 2015 Pearson Education, Inc. Ready for t cell receptor (TCR) Figure 16.8 The processing of T-dependent exogenous antigens. Phagocytosis by APC Exogenous pathogen with antigens Cells use toll-like receptors or NODs as surveillance for PAMPs. The patterns in PAMPs are the antigens MHC II protein– epitope complex 1 MHC II protein in membrane of vesicle Epitopes in phagolysosome 2 Vesicles fuse and epitopes bind to complementary MHC II molecules. 3 Vesicle fuses with cytoplasmic membrane. MHC II protein– epitope complexes on cell surface Cytoplasmic membrane 4 MHC II protein–epitope complexes are displayed on cytoplasmic membranes of antigenpresenting cell. © 2015 Pearson Education, Inc. Ready for t cell receptor (TCR) Antigen Processing and Presentation: Steps video © 2015 Pearson Education, Inc. Antigen Processing and Presentation: MHC video © 2015 Pearson Education, Inc. Elements of Adaptive Immunity • T Lymphocytes (T Cells) and Preparation for an Adaptive Immune Response • Types of T lymphocytes • Based on surface glycoproteins and characteristic functions • Cytotoxic T lymphocyte • Directly kills other cells • Helper T lymphocyte • Helps regulate B cells and cytotoxic T cells • Includes type 1 and type 2 helper T cells • Regulatory T lymphocyte • Represses adaptive immune responses © 2015 Pearson Education, Inc. Cell-Mediated Immunity: Helper T Cells video © 2015 Pearson Education, Inc. © 2015 Pearson Education, Inc. Elements of Adaptive Immunity • T Lymphocytes (T Cells) and Preparation for an Adaptive Immune Response • Clonal deletion • Vital that immune responses not be directed against autoantigens • Body eliminates self-reactive lymphocytes • Lymphocytes that react to autoantigens undergo apoptosis © 2015 Pearson Education, Inc. Figure 16.9 Clonal deletion of T cells. Stem cell (in red bone marrow) 1 Thymus T cells 2 TCRs with differently shaped binding sites MHC Epitope 3 Recognize MHC? Thymus Thymus cells cells No Yes Receive survival signal 4 Recognize MHC-autoantigen? Apoptosis No Yes Few Most Apoptosis Repertoire of immature Tc cells © 2015 Pearson Education, Inc. Regulatory T cell (Tr) 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 © 2015 Pearson Education, Inc. Elements of Adaptive Immunity • B Lymphocytes (B Cells) and Antibodies • Specificity of the B cell receptor (BCR) • Each B lymphocyte has multiple copies of the B cell receptor (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 • The entire repertoire of an individual’s BCRs is capable of recognizing millions of different epitopes © 2015 Pearson Education, Inc. Figure 16.10 B cell receptor (BCR). Epitope Heavy chain Light chain Antigenbinding sites Variable region Disulfide bond Cytoplasmic membrane of B lymphocyte Transmembrane portion of BCR Cytoplasm © 2015 Pearson Education, Inc. 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 antigen-binding sites and antigen specificity identical to the BCR of the activated B cell © 2015 Pearson Education, Inc. Figure 16.11 Basic antibody structure. Very flexible arms and hinge (unstructured regions) to allow it to attack antigen from many angles and more than one antibody pile on antigen Arm (Fab) Antigen-binding sites Light chain Variable region of heavy chain Hinge S S SS Constant region of light chain Constant region of heavy chain Stem (Fc) Heavy chains © 2015 Pearson Education, Inc. Hinge Variable region of light chain Arm (Fab) Stem (Fc) 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) © 2015 Pearson Education, Inc. Figure 16.12 Five functions of antibodies. Bacterium Adhesin proteins Toxin Virus Neutralization Agglutination NK lymphocyte Pseudopod of phagocyte Fcreceptor protein Perforin allows granzyme to enter, triggers apoptosis and lysis Fcreceptor protein Antibody-dependent cellular cytotoxicity (ADCC) Opsonization Bacteria die Oxidation © 2015 Pearson Education, Inc. Opson in ancient Greece referred to the delicious side-dish of any meal Elements of Adaptive Immunity • 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 © 2015 Pearson Education, Inc. Elements of Adaptive Immunity • B Lymphocytes (B Cells) and Antibodies • 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 © 2015 Pearson Education, Inc. © 2015 Pearson Education, Inc. Elements of Adaptive Immunity • B Lymphocytes (B Cells) and Antibodies • Clonal deletion of B cells • Occurs in the bone marrow • Similar to deletion of T cells • Self-reactive B cells may become inactive or change their BCR © 2015 Pearson Education, Inc. Figure 16.13 Clonal deletion of B cells. Stem cell (in red bone marrow) 1 B cells 2 BCRs with 3 differently shaped binding sites Cell with autoantigens Cell with autoantigens 4 Apoptosis Blood vessel © 2015 Pearson Education, Inc. To spleen 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 © 2015 Pearson Education, Inc. Elements of Adaptive Immunity • Immune System Cytokines • Interleukins (ILs) • Signal among leukocytes • L-1 from macrophages to lymphs • IL-2 from T- helpers to T-cytoxic • IL-4 from T-helpers to B cells • 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 (can come from leukocytes or from bacteria themselves like the LPSs) © 2015 Pearson Education, Inc. © 2015 Pearson Education, Inc. Cell-Mediated Immunity: Cytotoxic T Cells Cell-Mediated Immunity: Helper T Cells More videos © 2015 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 © 2015 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 • Antigen presentation • Helper T cell differentiation • Clonal expansion • Self-stimulation © 2015 Pearson Education, Inc. Figure 16.14 Activation of a clone of cytotoxic T (Tc) cells. Cool video of cellmediated immunity in action: cytoxic T cell taking down an infected cell probably by binding to epitope on the MHC I http://www.hhmi.org/bioi nteractive/ctl-killingtarget-cell Dendritic cell 1 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 – activating IL-2 receptor (IL-2R) 2 Th differentiation IL-2 3 Clonal expansion Th1 cell IL-2R IL-2 IL-2R Memory T cell Active Tc cells IL-2 4 Self-stimulation Active Tc cells IL-2 © 2015 Pearson Education, Inc. Kill the infected cell Figure 16.15a A cell-mediated immune response. Active cytotoxic T (Tc) cell TCR Viral epitope MHC I protein Virally infected cell Intracellular virus © 2015 Pearson Education, Inc. CD8 Cell-Mediated Immune Responses • Activation of Cytotoxic T Cell Clones and Their Functions • Cytotoxic T cells kills their targets by two pathways • Perforin-granzyme pathway • Involves synthesis of killing proteins • CD95 pathway • Mediated by a glycoprotein on the body’s cells © 2015 Pearson Education, Inc. Figure 16.15b-c A cell-mediated immune response. Tc cell Perforin Granzyme Tc cell CD95L Perforin complex (pore) Inactive apoptotic enzymes Virally infected cell © 2015 Pearson Education, Inc. Granzymes activate apoptotic enzymes Active enzymes induce apoptosis CD95 Inactive apoptotic enzymes Virally infected cell Enzymatic portion of CD95 becomes active Active enzymes induceapoptosis Cell-Mediated Immune Responses • Memory T Cells • Some activated T cells become memory T cells • Persist for months or years in lymphoid tissues • Immediately functional upon subsequent contacts with epitope-MHC complex specific to its TCR • Memory response is more effective than the primary response © 2015 Pearson Education, Inc. Cell-Mediated Immune Responses • T Cell Regulation • Regulation needed to prevent T cell response to autoantigens • T cells require additional signals from an antigen-presenting cell • Interaction of the T cell and antigen-presenting cell stimulates the T cell to respond to the antigen • Regulatory T cells also moderate cytotoxic T cell activity © 2015 Pearson Education, Inc. Antibody Immune Responses • Antibody immune responses mounted against exogenous pathogens and toxins • Activates only in response to specific pathogens © 2015 Pearson Education, Inc. Antibody Immune Responses • Inducement of T-Independent Antibody Immunity • T-independent antigens • Have many identical, repeating epitopes • Induce antibody response without assistance of helper T cells © 2015 Pearson Education, Inc. Figure 16.16 The effects of the binding of a T-independent antigen by a B cell. Polysaccharide with repeating subunits BCRs B cell Plasma cells Antibodies © 2015 Pearson Education, Inc. Figure 16.17 A plasma cell. Rough endoplasmic Nucleus reticulum © 2015 Pearson Education, Inc. Golgi body Antibody Immune Responses • Inducement of T-Independent Antibody Immunity • T-independent immunity is weak, disappears quickly, and induces little memory • T-independent responses are stunted in children • Can cause childhood diseases that are rare in adults © 2015 Pearson Education, Inc. Antibody Immune Responses • Inducement of T-Dependent Antibody Immunity with Clonal Selection • T-dependent antigens • Are small and lack repetitive epitopes • Immune responses against them require the assistance of helper T cells • Th2 cells induce B cells that recognize the same antigen © 2015 Pearson Education, Inc. Figure 16.18 A T-dependent antibody immune response. Repertoire of Th cells (CD4 cells) Th cell CD4 TCR CD28 CD4 Epitope CD80 (or CD86) MHC II TCRs APC 1 APC presents antigen to Th cells for Th activation and cloning. APC 2 Th cell differentiates into Th2 cell. Th cell clones CCR3 CCR4 IL-4 Th2 cell MHC II proteins Th2 cell CD4 Th2 cell TCR CD40L Epitope MHC II CD40 IL-4 B cell Repertoire of B cells 3 Th2 cell activates B cell. Clone of plasma cells 4 Antibodies © 2015 Pearson Education, Inc. Memory B cells Humoral Immunity: Primary Immune Response Humoral Immunity: Sec …
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