How do immune cells of animals recognize foreign cells? Fig 43.1 How do immune cells of animals recognize foreign cells? For the Cell Biology Video Leukocyte Adhesion and Rolling, go to Animation and Video Files. 1.5 µm

Animal Immunity INNATE IMMUNITY Barrier defenses: Internal defenses: Pathogens (microorganisms and viruses) INNATE IMMUNITY Barrier defenses: Skin Mucous membranes Secretions • Recognition of traits shared by broad ranges of pathogens, using a small set of receptors Non-specific Internal defenses: Phagocytic cells Antimicrobial proteins Inflammatory response Natural killer cells • Rapid response Figure 43.2 Overview of animal immunity ACQUIRED IMMUNITY Humoral response: Antibodies defend against infection in body fluids. • Recognition of traits specific to particular pathogens, using a vast array of receptors Cell-mediated response: Cytotoxic lymphocytes defend against infection in body cells. • Slower response

Phagocytosis Vacuole Lysosome Microbes PHAGOCYTIC CELL Containing hydrolytic enzymes Figure 43.3 Phagocytosis

TLR signaling EXTRACELLULAR FLUID Lipopolysaccharide Helper protein Flagellin TLR4 WHITE BLOOD CELL TLR5 VESICLE TLR9 CpG DNA Figure 43.6 TLR signaling Inflammatory responses TLR3 ds RNA

Lymphatic System Interstitial fluid Adenoid Tonsil Blood capillary nodes Spleen Tissue cells Lymphatic vessel Peyer’s patches (small intestine) Appendix Figure 43.7 The human lymphatic system Lymphatic vessels Lymph node Masses of defensive cells

3. 1. 2. Major events in a local Inflammatory Response Pathogen Splinter Chemical signals Macrophage Fluid Mast cell Capillary Phagocytosis Figure 43.8 Major events in a local inflammatory response For the Cell Biology Video Chemotaxis of a Neutrophil, go to Animation and Video Files. Red blood cells Phagocytic cell

Antigen receptors on lymphocytes binding site Antigen- binding site Antigen- binding site V Disulfide bridge V V V Variable regions C V V C Constant regions C C C C Light chain Transmembrane region Plasma membrane Heavy chains  chain  chain Figure 43.9 Antigen receptors on lymphocytes Disulfide bridge B cell Cytoplasm of B cell Cytoplasm of T cell T cell B cell receptor T cell receptor

Epitopes = antigen determinants binding sites Epitopes (antigenic determinants) Antigen-binding sites Antibody A Antigen V V Antibody C V V C C C C Figure 43.10 Epitopes (antigenic determinants) Antibody B

Antigen Presentation by an MHC molecule Top view: binding surface exposed to antigen receptors Antigen Class I MHC molecule Antigen Figure 43.11 Antigen presentation by an MHC molecule Plasma membrane of infected cell

Interaction of T cells with Antigen-Presenting Cells Infected cell Microbe Antigen- presenting cell 1 Antigen associates with MHC molecule Antigen fragment Antigen fragment 1 1 Class I MHC molecule Class II MHC molecule 2 2 T cell receptor T cell receptor 2 T cell recognizes combination Figure 43.12 The interaction of T cells with antigen-presenting cells (a) Cytotoxic T cell (b) Helper T cell

Clonal Selection of B cells Antigen molecules B cells that differ in antigen specificity Antigen receptor Figure 43.14 Clonal selection of B cells Antibody molecules Clone of memory cells Clone of plasma cells = effectors

Antibody concentration Primary immune response to antigen A produces antibodies to A. Secondary immune response to antigen A produces antibodies to A. Primary immune response to antigen B produces antibodies to B. 104 103 Antibody concentration (arbitrary units) Antibodies to A 102 Antibodies to B 101 Figure 43.15 The specificity of immunological memory 100 7 14 21 28 35 42 49 56 Exposure to antigen A Exposure to antigens A and B Time (days)

Acquired Immune Response Humoral (antibody-mediated) immune response Cell-mediated immune response Key Antigen (1st exposure) + Stimulates Gives rise to Engulfed by Antigen- presenting cell + + + B cell Helper T cell Cytotoxic T cell + + Memory Helper T cells + + + Figure 43.16 An overview of the acquired immune response Antigen (2nd exposure) + Memory Cytotoxic T cells Active Cytotoxic T cells Plasma cells Memory B cells Secreted antibodies Defend against extracellular pathogens by binding to antigens, thereby neutralizing pathogens or making them better targets for phagocytes and complement proteins. Defend against intracellular pathogens and cancer by binding to and lysing the infected cells or cancer cells.

Acquired Immune Response Humoral (antibody-mediated) immune response Key Antigen (1st exposure) + Stimulates Gives rise to Engulfed by Antigen- presenting cell + + B cell Helper T cell + Memory Helper T cells + + Figure 43.16 An overview of the acquired immune response Antigen (2nd exposure) Plasma cells Memory B cells + Secreted antibodies Defend against extracellular pathogens

Acquired Immune Response Cell-mediated immune response Antigen (1st exposure) Key + Stimulates Gives rise to Engulfed by Antigen- presenting cell + + Helper T cell Cytotoxic T cell + Memory Helper T cells Figure 43.16 An overview of the acquired immune response + + Antigen (2nd exposure) Active Cytotoxic T cells + Memory Cytotoxic T cells Defend against intracellular pathogens

The central role of helper T cells in humoral and cell-mediated immune responses Antigen- presenting cell Peptide antigen Bacterium Class II MHC molecule CD4 TCR (T cell receptor) Helper T cell Cytokines Positive Feedback … + Humoral immunity = secretion of antibodies by plasma cells. + Cell-mediated immunity = attack on infected cells. Figure 43.17 The central role of helper T cells in humoral and cell-mediated immune responses + + B cell Cytotoxic T cell

3. lysis 1. 2. The killing action of cytotoxic T cells Released cytotoxic T cell Cytotoxic T cell Perforin Granzymes CD8 TCR Dying target cell Class I MHC molecule Pore Figure 43.18 The killing action of cytotoxic T cells For the Discovery Video Fighting Cancer, go to Animation and Video Files. Target cell Peptide antigen

B cell activation in the humoral immune response Antigen-presenting cell Bacterium Peptide antigen B cell Class II MHC molecule Secreted antibody molecules + Clone of plasma cells TCR CD4 Cytokines Endoplasmic reticulum of plasma cell Activated helper T cell Helper T cell Clone of memory B cells Figure 43.19 B cell activation in the humoral immune response 2 µm

The five antibody, or immunoglobulin (Ig), classes Class of Immuno- globulin (Antibody) Distribution Function IgM (pentamer) First Ig class produced after initial exposure to antigen; then its concentration in the blood declines Promotes neutraliza- tion and cross- linking of antigens; very effective in complement system activation J chain IgG (monomer) Most abundant Ig class in blood; also present in tissue fluids Promotes opsoniza- tion, neutralization, and cross-linking of antigens; less effec- tive in activation of complement system than IgM Only Ig class that crosses placenta, thus conferring passive immunity on fetus IgA (dimer) Present in secretions such as tears, saliva, mucus, and breast milk Provides localized defense of mucous membranes by cross-linking and neutralization of antigens J chain Presence in breast milk confers passive immunity on nursing infant Secretory component Figure 43.20 The five antibody, or immunoglobulin (Ig), classes IgE (monomer) Present in blood at low concen- trations Triggers release from mast cells and basophils of hista- mine and other chemicals that cause allergic reactions IgD (monomer) Present primarily on surface of B cells that have not been exposed to antigens Acts as antigen receptor in the antigen-stimulated proliferation and differentiation of B cells (clonal selection) Trans- membrane region

Antibody-mediated mechanisms of antigen disposal Activation of complement system and pore formation Viral neutralization Opsonization Bacterium Complement proteins Virus Formation of membrane attack complex Flow of water and ions Macrophage Pore Figure 43.21 Antibody-mediated mechanisms of antigen disposal Foreign cell

Passive immunization of an infant occurs during breast-feeding Figure 43.22 Passive immunization of an infant occurs during breast-feeding For the Discovery Video Vaccines, go to Animation and Video Files.

Mast cells, IgE, and the allergic response Histamine Allergen Granule Figure 43.23 Mast cells, IgE, and the allergic response Mast cell

X-ray of a hand deformed by rheumatoid arthritis Figure 43.24 X-ray of a hand deformed by rheumatoid arthritis

Helper T cell concentration The progress of an untreated HIV infection Latency AIDS Relative antibody concentration 800 Relative HIV concentration 600 Helper T cell concentration in blood (cells/mm3) Helper T cell concentration 400 Figure 43.26 The progress of an untreated HIV infection 200 1 2 3 4 5 6 7 8 9 10 Years after untreated infection

Review Stem cell Cell division and gene rearrangement Elimination of self-reactive B cells Antigen Clonal selection Formation of activated cell populations Antibody Memory cells Effector B cells Microbe Receptors bind to antigens

You should now be able to: Distinguish between innate and acquired immunity. Name and describe four types of phagocytic cells. Describe the inflammation response.

Distinguish between the following pairs of terms: antigens and antibodies; antigen and epitope; B lymphocytes and T lymphocytes; antibodies and B cell receptors; primary and secondary immune responses; humoral and cell-mediated response; active and passive immunity. Explain how B lymphocytes and T lymphocytes recognize specific antigens. Explain why the antigen receptors of lymphocytes are tested for self-reactivity.

Describe clonal selection and distinguish between effector cells and memory cells. Describe the cellular basis for immunological memory. Explain how a single antigen can provoke a robust humoral response. Compare the processes of neutralization and opsonization.

Describe the role of MHC in the rejection of tissue transplants. Describe an allergic reaction, including the roles of IgE, mast cells, and histamine. Describe some of the mechanisms that pathogens have evolved to thwart the immune response of their hosts. List strategies that can reduce the risk of HIV transmission.