Chapter 43 The Immune System

Objective: You will be able to list examples of nonspecific mechanical and cellular defenses. Do Now Read AND outline p. 898-903.

broad range of microbes Figure 43.2 Overview of vertebrate defenses against bacteria, viruses, and other pathogens INNATE IMMUNITY Rapid responses to a broad range of microbes ACQUIRED IMMUNITY Slower responses to specific microbes External defenses Internal defenses Skin Mucous membranes Secretions Phagocytic cells Antimicrobial proteins Inflammatory response Natural killer cells Humoral response (antibodies) Cell-mediated response (cytotoxic lymphocytes) Invading microbes (pathogens)

Figure 43.3 External innate defense by mucous membranes

Figure 43.1 A macrophage (blue) ingesting a yeast cell (green)

Figure 43.4 Phagocytosis Microbes MACROPHAGE Lysosome Vacuole containing enzymes 1 2 3 4 5 6 Pseudopodia surround microbes. are engulfed into cell. microbes forms. and lysosome fuse. Toxic compounds and lysosomal destroy microbes. Microbial debris is released by exocytosis.

Figure 43.6 Major events in the local inflammatory response Pathogen Pin Macrophage Chemical signals Capillary Phagocytic cells Red blood cell Blood clotting elements Blood clot Phagocytosis Fluid, antimicrobial proteins, and clotting elements move from the blood to the site. Clotting begins. 2 Chemical signals released by activated macrophages and mast cells at the injury site cause nearby capillaries to widen and become more permeable. 1 Chemokines released by various kinds of cells attract more phagocytic cells from the blood to the injury site. 3 Neutrophils and macrophages phagocytose pathogens and cell debris at the site, and the tissue heals. 4

Objective: You will be able to describe the structure of lymphocytes and explain how they work in specific immunity. Do Now: Read “Lymphocytes provide the…” on p. 904-905 Explain how lymphocytes are able to carry out specific immunity

Figure 43.5 The human lymphatic system 1 2 3 4 Interstitial fluid bathing the tissues, along with the white blood cells in it, continually enters lymphatic capillaries. Fluid inside the lymphatic capillaries, called lymph, flows through lymphatic vessels throughout the body. Within lymph nodes, microbes and foreign particles present in the circulating lymph encounter macro- phages, dendritic cells, and lymphocytes, which carry out various defensive actions. Lymphatic vessels return lymph to the blood via two large ducts that drain into veins near the shoulders. Adenoid Tonsil Lymph nodes Spleen Peyer’s patches (small intestine) Appendix Lymphatic vessels node Masses of lymphocytes and macrophages Tissue cells vessel Blood capillary Interstitial fluid

Figure 43.10 Overview of lymphocyte development Bone marrow Lymphoid stem cell B cell Thymus T cell Blood, lymph, and lymphoid tissues (lymph nodes, spleen, and others)

Figure 43.7 Epitopes (antigenic determinants) binding sites Antibody A Antigen Antibody B Antibody C Epitopes (antigenic determinants)

Figure 43.8 Antigen receptors on lymphocytes binding site binding site Disulfide bridge Light chain Heavy chains Cytoplasm of B cell b chain Disulfide bridge a chain V C T cell A T cell receptor consists of one chain and one b chain linked by a disulfide bridge. (b) A B cell receptor consists of two identical heavy chains and two identical light chains linked by several disulfide bridges. (a) Variable regions Constant Transmembrane region Plasma membrane B cell Cytoplasm of T cell

Figure 43.11 Immunoglobulin gene rearrangement DNA of undifferentiated B cell DNA of differentiated pre-mRNA mRNA Cap Transcription of resulting permanently rearranged, functional gene RNA processing (removal of intron; addition of cap and poly (A) tail) B cell receptor Light-chain polypeptide Intron Variable region Constant V1 V2 V3 V4–V39 V40 J1 J2 J3 J4 J5 V C 2 3 4 Translation Poly (A) Deletion of DNA between a V segment and J segment and joining of the segments 1

Figure 43.12 Clonal selection of B cells Antigen molecules Antigen receptor B cells that differ in antigen specificity Antibody molecules Clone of memory cells Clone of plasma cells Some proliferating cells develop into long-lived memory cells that can respond rapidly upon subsequent exposure to the same antigen. bind to the antigen receptors of only one of the three B cells shown. The selected B cell proliferates, forming a clone of identical cells bearing receptors for the selecting antigen. Some proliferating cells develop into short-lived plasma cells that secrete antibodies specific for the antigen.

Figure 43.13 The specificity of immunological memory Antibodies to A to B Antibody concentration (arbitrary units) 104 103 102 101 100 7 14 21 28 35 42 49 56 Time (days) Day 1: First exposure to antigen A 1 Primary response to produces anti- bodies to A 2 Day 28: Second exposure to antigen A; first antigen B 3 Secondary response to anti- gen A produces antibodies to A; primary response to anti- gen B produces antibodies to B 4

Figurze 43.15 The central role of helper T cells in humoral and cell-mediated immune responses After a dendritic cell engulfs and degrades a bacterium, it displays bacterial antigen fragments (peptides) complexed with a class II MHC molecule on the cell surface. A specific helper T cell binds to the displayed complex via its TCR with the aid of CD4. This interaction promotes secretion of cytokines by the dendritic cell. Proliferation of the T cell, stimulated by cytokines from both the dendritic cell and the T cell itself, gives rise to a clone of activated helper T cells (not shown), all with receptors for the same MHC–antigen complex. The cells in this clone secrete other cytokines that help activate B cells and cytotoxic T cells. Cell-mediated immunity (attack on infected cells) Humoral (secretion of antibodies by plasma cells) Dendritic cell Bacterium Peptide antigen Class II MHC molecule TCR CD4 Helper T cell Cytokines Cytotoxic T cell B cell 1 2 3

Figure 43.12 Clonal selection of TH cells Antigen molecules Antigen receptor B cells that differ in antigen specificity Antibody molecules Clone of memory cells Clone of plasma cells Some proliferating cells develop into long-lived memory cells that can respond rapidly upon subsequent exposure to the same antigen. bind to the antigen receptors of only one of the three B cells shown. The selected B cell proliferates, forming a clone of identical cells bearing receptors for the selecting antigen. Some proliferating cells develop into short-lived plasma cells that secrete antibodies specific for the antigen. X

Group Choice!!!! You will be graded on the content!!!! You will create a group project involving the steps of immunity Choose to complete one of the following: SKIT: Script a skit (with roles for other members of the class) which will portray the elements of immunological response to a specific situation. MODEL: Build a 3-dimensional physical model to convey the principles of immunological response. Media: Create a movie trailer, news story or show about the immune response. You will be graded on the content!!!!

Objective: You will be able to discuss the steps of cell-mediated and humoral immunity. Do Now: Read p. 908 – 909 only “Immune responses” Differentiate between cell-mediated and humoral immunity

Figure 43.17 Humoral immune response (layer 1) Macrophage Bacterium Peptide antigen Class II MHC molecule TCR Helper T cell CD4

Figure 43.17 Humoral immune response (layer 2) B cell Bacterium Peptide antigen Class II MHC molecule TCR Helper T cell CD4 Activated helper T cell Cytokines Macrophage

Figure 43.17 Humoral immune response (layer 3) 2 1 3 B cell Bacterium Peptide antigen Class II MHC molecule TCR Helper T cell CD4 Activated helper T cell Clone of memory B cells Cytokines Clone of plasma cells Secreted antibody molecules Endoplasmic reticulum of plasma cell Macrophage

Figure 43.19 Antibody-mediated mechanisms of antigen disposal Binding of antibodies to antigens inactivates antigens by Viral neutralization (blocks binding to host) and opsonization (increases phagocytosis) Agglutination of antigen-bearing particles, such as microbes Precipitation of soluble antigens Activation of complement system and pore formation Bacterium Virus Bacteria Soluble antigens Foreign cell Complement proteins MAC Pore Enhances Phagocytosis Leads to Cell lysis Macrophage

Figurze 43.15 The central role of helper T cells in humoral and cell-mediated immune responses After a dendritic cell engulfs and degrades a bacterium, it displays bacterial antigen fragments (peptides) complexed with a class II MHC molecule on the cell surface. A specific helper T cell binds to the displayed complex via its TCR with the aid of CD4. This interaction promotes secretion of cytokines by the dendritic cell. Proliferation of the T cell, stimulated by cytokines from both the dendritic cell and the T cell itself, gives rise to a clone of activated helper T cells (not shown), all with receptors for the same MHC–antigen complex. The cells in this clone secrete other cytokines that help activate B cells and cytotoxic T cells. Cell-mediated immunity (attack on infected cells) Humoral (secretion of antibodies by plasma cells) Dendritic cell Bacterium Peptide antigen Class II MHC molecule TCR CD4 Helper T cell Cytokines Cytotoxic T cell B cell 1 2 3

Figure 43.12 Clonal selection of TC cells Antigen molecules Antigen receptor B cells that differ in antigen specificity Antibody molecules Clone of memory cells Clone of plasma cells Some proliferating cells develop into long-lived memory cells that can respond rapidly upon subsequent exposure to the same antigen. bind to the antigen receptors of only one of the three B cells shown. The selected B cell proliferates, forming a clone of identical cells bearing receptors for the selecting antigen. Some proliferating cells develop into short-lived plasma cells that secrete antibodies specific for the antigen. X

Figure 43.16 The killing action of cytotoxic T cells Perforin Granzymes CD8 TCR Class I MHC molecule Target cell Peptide antigen Pore Released cytotoxic T cell Apoptotic target cell Cancer Cytotoxic A specific cytotoxic T cell binds to a class I MHC–antigen complex on a target cell via its TCR with the aid of CD8. This interaction, along with cytokines from helper T cells, leads to the activation of the cytotoxic cell. 1 The activated T cell releases perforin molecules, which form pores in the target cell membrane, and proteolytic enzymes (granzymes), which enter the target cell by endocytosis. 2 The granzymes initiate apoptosis within the target cells, leading to fragmentation of the nucleus, release of small apoptotic bodies, and eventual cell death. The released cytotoxic T cell can attack other target cells. 3

Figure 43.9 The interaction of T cells with MHC molecules Infected cell Antigen fragment Class I MHC molecule T cell receptor Cytotoxic T cell (a) Microbe Antigen- presenting cell Class II MHC Helper T cell (b) 1 2 The combination of MHC molecule and antigen is recognized by a T cell, alerting it to the infection. A fragment of foreign protein (antigen) inside the cell associates with an MHC molecule and is transported to the cell surface.

Figure 43.14 An overview of the acquired immune response (layer 1) Humoral immune response Cell-mediated immune response First exposure to antigen Antigens engulfed and displayed by dendritic cells Activate Gives rise to Helper T cell Active and memory helper T cells

Figure 43.14 An overview of the acquired immune response (layer 2) Humoral immune response Cell-mediated immune response First exposure to antigen Antigens engulfed and displayed by dendritic cells Antigens displayed by infected cells Activate Gives rise to Helper T cell Cytotoxic T cell Active and memory helper T cells Memory cytotoxic T cells Active cytotoxic T cells Defend against infected cells, cancer cells, and transplanted tissues Secreted cytokines activate

Figure 43.14 An overview of the acquired immune response (layer 3) Humoral immune response Cell-mediated immune response First exposure to antigen Intact antigens Antigens engulfed and displayed by dendritic cells Antigens displayed by infected cells Activate Gives rise to B cell Helper T cell Cytotoxic T cell Plasma cells Memory B cells Active and memory helper T cells Memory cytotoxic T cells Active cytotoxic T cells Secrete antibodies that defend against pathogens and toxins in extracellular fluid Defend against infected cells, cancer cells, and transplanted tissues Secreted cytokines activate

Table 43.1 Blood Groups That Can and Cannot Be Safely Combined in Transfusion

Figure 43.20 Mast cells, IgE, and the allergic response IgE antibodies produced in response to initial exposure to an allergen bind to receptors or mast cells. 1 On subsequent exposure to the same allergen, IgE molecules attached to a mast cell recog- nize and bind the allergen. 2 Degranulation of the cell, triggered by cross-linking of adjacent IgE molecules, releases histamine and other chemicals, leading to allergy symptoms. 3 Allergen IgE Histamine Granule Mast cell