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PowerPoint® Lecture Slides prepared by Janice Meeking, Mount Royal College CHAPTER 21 The Immune System: Innate and Adaptive Body Defenses: Part B Copyright © 2010 Pearson Education, Inc. Copyright © 2010 Pearson Education, Inc. Copyright © 2010 Pearson Education, Inc. Copyright © 2010 Pearson Education, Inc. Antibodies • Immunoglobulins—gamma globulin portion of blood • Proteins secreted by plasma cells • Capable of binding specifically with antigen detected by B cells Copyright © 2010 Pearson Education, Inc. Basic Antibody Structure • T-or Y-shaped monomer • Two identical heavy (H) chains and two identical light (L) chains • Variable (V) regions: two identical antigenbinding sites • Constant (C) region of stem determines • The antibody class (IgM, IgA, IgD, IgG, or IgE) Copyright © 2010 Pearson Education, Inc. Antigen-binding site Heavy chain variable region Heavy chain constant region Light chain variable region Light chain constant region Disulfide bond Copyright © 2010 Pearson Education, Inc. Hinge region Stem region (a) Figure 21.14a Copyright © 2010 Pearson Education, Inc. Table 21.3 Copyright © 2010 Pearson Education, Inc. Table 21.3 Classical pathway Antigen-antibody complex + complex Opsonization: coats pathogen surfaces, which enhances phagocytosis Insertion of MAC and cell lysis (holes in target cell’s membrane) Alternative pathway Spontaneous activation + Stabilizing factors (B, D, and P) + No inhibitors on pathogen surface Enhances inflammation: stimulates histamine release, increases blood vessel permeability, attracts phagocytes by chemotaxis, etc. Pore Complement proteins (C5b–C9) Membrane of target cell Copyright © 2010 Pearson Education, Inc. Figure 21.6 Generating Antibody Diversity • Billions of antibodies result from somatic recombination of gene segments • Hypervariable regions of some genes increase antibody variation through somatic mutations • Each plasma cell can switch the type of H chain produced, making an antibody of a different class Copyright © 2010 Pearson Education, Inc. Antibody Targets • Antibodies inactivate and tag antigens • Form antigen-antibody (immune) complexes • Defensive mechanisms used by antibodies 1. Neutralization 2. Agglutination (1 and 2 most important) 3. Precipitation 4. Complement fixation Copyright © 2010 Pearson Education, Inc. Adaptive defenses Humoral immunity Antigen Antigen-antibody complex Antibody Inactivates by Neutralization (masks dangerous parts of bacterial exotoxins; viruses) Agglutination (cell-bound antigens) Enhances Phagocytosis Fixes and activates Precipitation (soluble antigens) Enhances Complement Leads to Inflammation Cell lysis Chemotaxis Histamine release Copyright © 2010 Pearson Education, Inc. Figure 21.15 Cell-Mediated Immune Response • T cells provide defense against intracellular antigens • Two types of surface receptors of T cells • T cell antigen receptors • Cell differentiation glycoproteins • CD4 or CD8 • Play a role in T cell interactions with other cells Copyright © 2010 Pearson Education, Inc. Cell-Mediated Immune Response • Major types of T cells • CD4 cells become helper T cells (TH) when activated by MHC II • CD8 cells become cytotoxic T cells (TC) when activated by MHC I destroy cells harboring foreign antigens • Other types of T cells • Regulatory T cells (TREG) • Memory T cells Copyright © 2010 Pearson Education, Inc. Comparison of Humoral and Cell-Mediated Response • Antibodies of the humoral response • The simplest ammunition of the immune response • Targets • Bacteria and molecules in extracellular environments (body secretions, tissue fluid, blood, and lymph) Copyright © 2010 Pearson Education, Inc. Comparison of Humoral and Cell-Mediated Response • T cells of the cell-mediated response • Recognize and respond only to processed fragments of antigen displayed on the surface of body cells • MHC I (CD8) and MHC II (APC + CD4) • Targets 1. Body cells infected by viruses or bacteria 2. Abnormal or cancerous cells 3. Cells of infused or transplanted foreign tissue Copyright © 2010 Pearson Education, Inc. MHC Proteins • Two types of MHC proteins are important to T cell activation • Class I MHC proteins - displayed by all cells except RBCs • Class II MHC proteins – displayed by APCs (dendritic cells, macrophages and B cells) Copyright © 2010 Pearson Education, Inc. Class I MHC Proteins • Bind with fragment of a protein synthesized in the cell (endogenous antigen) • Endogenous antigen is a self-antigen in a normal cell; a non-self antigen in an infected or abnormal cell • Informs cytotoxic T cells of the presence of microorganisms hiding in cells (cytotoxic T cells ignore displayed self-antigens) Copyright © 2010 Pearson Education, Inc. Class II MHC Proteins • Bind with fragments of exogenous antigens that have been engulfed and broken down in a phagolysosome • Recognized by helper T cells Copyright © 2010 Pearson Education, Inc. Adaptive defenses Cellular immunity Immature lymphocyte Red bone marrow T cell receptor Class II MHC protein T cell receptor Maturation CD4 cell Thymus Activation APC (dendritic cell) Activation Memory cells CD4 Class I MHC protein CD8 cell APC (dendritic cell) CD8 Lymphoid tissues and organs Helper T cells (or regulatory T cells) Copyright © 2010 Pearson Education, Inc. Effector cells Blood plasma Cytotoxic T cells Figure 21.16 T Cell Activation • APCs (most often a dendritic cell) migrate to lymph nodes and other lymphoid tissues to present their antigens to T cells • T cell activation is a two-step process 1. Antigen binding 2. Co-stimulation Copyright © 2010 Pearson Education, Inc. T Cell Activation: Antigen Binding • CD4 and CD8 cells bind to different classes of MHC proteins (MHC restriction) • CD4 cells bind to antigen linked to class II MHC proteins of APCs • CD8 cells are activated by antigen fragments linked to class I MHC of APCs Copyright © 2010 Pearson Education, Inc. Adaptive defenses Cellular immunity 1 Dendritic cell Viral antigen Dendritic cell T cell receptor (TCR) Clone formation Class lI MHC protein displaying processed viral antigen CD4 protein engulfs an exogenous antigen, processes it, and displays its fragments on class II MHC protein. 2 Immunocompetent CD4 cell recognizes antigen-MHC complex. Both TCR and CD4 protein bind Immunocom- to antigen-MHC complex. petent CD4 T cell 3 CD4 cells are activated, proliferate (clone), and become memory and effector cells. Helper T memory cell Copyright © 2010 Pearson Education, Inc. Activated helper T cells Figure 21.18 Cytokines • Mediate cell development, differentiation, and responses in the immune system • Include interleukins and interferons • Interleukin 1 (IL-1) released by macrophages co-stimulates bound T cells to • Release interleukin 2 (IL-2) • Synthesize more IL-2 receptors Copyright © 2010 Pearson Education, Inc. Cytokines • IL-2 is a key growth factor, acting on cells that release it and other T cells • Encourages activated T cells to divide rapidly • Used therapeutically to treat melanoma and kidney cancers • Other cytokines amplify and regulate innate and adaptive responses Copyright © 2010 Pearson Education, Inc. Roles of Helper T (TH or 4) Cells • Play a central role in the adaptive immune response • Once primed by APC presentation of antigen, they • Help activate T and B cells • Induce T and B cell proliferation • Activate macrophages and recruit other immune cells • Without TH, there is no immune response Copyright © 2010 Pearson Education, Inc. TH cell help in humoral immunity Activated helper T cell 1 TH cell binds with the Helper T cell CD4 protein self-nonself complexes of a B cell that has encountered its antigen and is displaying it on MHC II on its surface. MHC II protein of B cell displaying processed antigen 2 TH cell releases T cell receptor (TCR) IL- 4 and other cytokines interleukins as co-stimulatory signals to complete B cell activation. B cell (being activated) (a) Copyright © 2010 Pearson Education, Inc. Figure 21.19a Figure 21.19b The central role of helper T cells in mobilizing both humoral and cellular immunity. TH cell help in cell-mediated immunity CD4 protein Helper T cell Class II MHC protein APC (dendritic cell) 1 Previously activated TH cell binds dendritic cell. 2 TH cell stimulates IL-2 dendritic cell to express co-stimulatory molecules (not shown) needed to activate CD8 cell. 3 Dendritic cell can Class I MHC protein (b) Copyright © 2010 Pearson Education, Inc. CD8 protein CD8 T cell now activate CD8 cell with the help of interleukin 2 secreted by TH cell. Roles of Cytotoxic T (TC or 8) Cells • Directly attack and kill other cells • Activated TC cells circulate in blood and lymph and lymphoid organs in search of body cells displaying antigen they recognize Copyright © 2010 Pearson Education, Inc. Roles of Cytotoxic T(TC) Cells • Targets • Virus-infected cells • Cells with intracellular bacteria or parasites • Cancer cells • Foreign cells (transfusions or transplants) • Bind to a self-nonself complex • Can destroy all infected or abnormal cells Copyright © 2010 Pearson Education, Inc. Figure 21.19 The central role of helper T cells in mobilizing both humoral and cellular immunity. Humoral immunity Cellular immunity Adaptive defenses Activated helper T cell 1 T cell binds with the H self-nonself complexes of a B cell that has encountered its antigen and is displaying it on MHC II on its surface. T cell receptor (TCR) Helper T cell CD4 protein MHC II protein of B cell displaying processed antigen 2 TH cell releases interleukins as co-stimulatory signals to complete B cell activation. IL- 4 and other cytokines B cell (being activated) (a) TH cell help in cell-mediated immunity CD4 protein Helper T cell 1 Previously activated T H cell binds dendritic cell. Class II MHC protein APC (dendritic cell) IL-2 2 TH cell stimulates dendritic cell to express co-stimulatory molecules (not shown) needed to activate CD8 cell. 3 Dendritic cell can now Class I MHC protein (b) Copyright © 2010 Pearson Education, Inc. CD8 protein CD8 T cell activate CD8 cell with the help of interleukin 2 secreted by TH cell. Figure 21.20a Cytotoxic T cells attack infected and cancerous cells. Adaptive defenses Cytotoxic T cell (TC) Cellular immunity 1 TC binds tightly to the target cell when it identifies foreign antigen on MHC I proteins. granzyme molecules from its granules by exocytosis. Granule Perforin 3 Perforin molecules insert into the target cell membrane, polymerize, and form transmembrane pores (cylindrical holes) similar to those produced by complement activation. TC cell membrane Target cell membrane Target cell 2 TC releases perforin and 4 Granzymes enter the Perforin pore Granzymes 5 The TC detaches and target cell via the pores. Once inside, these proteases degrade cellular contents, stimulating apoptosis. searches for another prey. (a) A mechanism of target cell killing by TC cells. Copyright © 2010 Pearson Education, Inc. Table 21.1 Inflammatory Chemicals Copyright © 2010 Pearson Education, Inc. Table 21.2 Summary of Innate Body Defenses (1 of 2) Copyright © 2010 Pearson Education, Inc. Table 21.2 Summary of Innate Body Defenses (2 of 2) Copyright © 2010 Pearson Education, Inc. Table 21.3 Immunoglobulin Classes (1 of 2) Copyright © 2010 Pearson Education, Inc. Table 21.3 Immunoglobulin Classes (2 of 2) Copyright © 2010 Pearson Education, Inc. Table 21.4 Selected Cytokines Copyright © 2010 Pearson Education, Inc. Table 21.5 Cells and Molecules of the Adaptive Immune Response (1 of 2) Copyright © 2010 Pearson Education, Inc. Table 21.5 Cells and Molecules of the Adaptive Immune Response (2 of 2) Copyright © 2010 Pearson Education, Inc.