Fig. 43-1 1.5 µm

Pathogens (microorganisms and viruses) Fig. 43-2 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 Internal defenses: Phagocytic cells Antimicrobial proteins Inflammatory response Natural killer cells • Rapid response 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

Fig. 43-3 Microbes PHAGOCYTIC CELL Vacuole Lysosome containing enzymes

Fig. 43-4

Fruit fly survival after infection by N. crassa fungi Fig. 43-5 RESULTS 100 Wild type 75 Mutant + drosomycin % survival 50 Mutant Mutant + defensin 25 24 48 72 96 120 Hours post-infection Fruit fly survival after infection by N. crassa fungi 100 75 Wild type Mutant + defensin % survival 50 Mutant + drosomycin Mutant 25 24 48 72 96 120 Hours post-infection Fruit fly survival after infection by M. luteus bacteria

Fruit fly survival after infection by N. crassa fungi Fig. 43-5a RESULTS 100 Wild type 75 Mutant + drosomycin % survival 50 Mutant + defensin Mutant 25 24 48 72 96 120 Hours post-infection Fruit fly survival after infection by N. crassa fungi

Fruit fly survival after infection by M. luteus bacteria Fig. 43-5b RESULTS 100 Wild type Mutant + defensin 75 % survival 50 Mutant + drosomycin Mutant 25 24 48 72 96 120 Hours post-infection Fruit fly survival after infection by M. luteus bacteria

EXTRACELLULAR FLUID Lipopolysaccharide Helper protein Flagellin TLR4 Fig. 43-6 EXTRACELLULAR FLUID Lipopolysaccharide Helper protein Flagellin TLR4 WHITE BLOOD CELL TLR5 VESICLE TLR9 CpG DNA Inflammatory responses TLR3 ds RNA

Interstitial fluid Adenoid Tonsil Blood capillary Lymph nodes Spleen Fig. 43-7 Interstitial fluid Adenoid Tonsil Blood capillary Lymph nodes Spleen Tissue cells Lymphatic vessel Peyer’s patches (small intestine) Appendix Lymphatic vessels Lymph node Masses of defensive cells

Pathogen Splinter Chemical signals Macrophage Mast cell Capillary Fig. 43-8-1 Pathogen Splinter Chemical signals Macrophage Mast cell Capillary Red blood cells Phagocytic cell

Pathogen Splinter Chemical signals Macrophage Fluid Mast cell Fig. 43-8-2 Pathogen Splinter Chemical signals Macrophage Fluid Mast cell Capillary Red blood cells Phagocytic cell

Pathogen Splinter Chemical signals Macrophage Fluid Mast cell Fig. 43-8-3 Pathogen Splinter Chemical signals Macrophage Fluid Mast cell Capillary Phagocytosis Red blood cells Phagocytic cell

Fig. 43-9 Antigen- binding site Antigen- binding site Antigen- binding 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 Disulfide bridge B cell Cytoplasm of B cell Cytoplasm of T cell T cell (a) B cell receptor (b) T cell receptor

Antigen- binding site Antigen- binding site V Disulfide bridge V V V Fig. 43-9a Antigen- binding site Antigen- binding site V Disulfide bridge V V V Variable regions C C Constant regions C C Light chain Transmembrane region Plasma membrane Heavy chains B cell Cytoplasm of B cell (a) B cell receptor

Antigen- binding site Variable regions V V Constant regions C C Fig. 43-9b Antigen- binding site Variable regions V V Constant regions C C Transmembrane region Plasma membrane  chain  chain Disulfide bridge Cytoplasm of T cell T cell (b) T cell receptor

Antigen-binding sites Fig. 43-10 Antigen- binding sites Epitopes (antigenic determinants) Antigen-binding sites Antibody A Antigen V V Antibody C V V C C C C Antibody B

Top view: binding surface exposed to antigen receptors Fig. 43-11 Top view: binding surface exposed to antigen receptors Antigen Class I MHC molecule Antigen Plasma membrane of infected cell

Infected cell Microbe Antigen- presenting cell 1 Antigen associates Fig. 43-12 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 (a) Cytotoxic T cell (b) Helper T cell

Variable region Constant region Fig. 43-13 DNA of undifferentiated B cell V37 V38 V39 V40 J1 J2 J3 J4 J5 Intron C 1 DNA deleted between randomly selected V and J segments DNA of differentiated B cell V37 V38 V39 J5 Intron C Functional gene 2 Transcription pre-mRNA V39 J5 Intron C 3 RNA processing B cell receptor mRNA Cap V39 J5 C Poly-A tail V V 4 Translation V V C C Light-chain polypeptide V C C C Variable region Constant region B cell

Antigen molecules B cells that differ in antigen specificity Antigen Fig. 43-14 Antigen molecules B cells that differ in antigen specificity Antigen receptor Antibody molecules Clone of memory cells Clone of plasma cells

Antibody concentration Fig. 43-15 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 101 100 7 14 21 28 35 42 49 56 Exposure to antigen A Exposure to antigens A and B Time (days)

Fig. 43-16 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 + + + 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.

Humoral (antibody-mediated) immune response Fig. 43-16a 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 + + Antigen (2nd exposure) Memory B cells Plasma cells + Secreted antibodies Defend against extracellular pathogens

Cell-mediated immune response Fig. 43-16b 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 + + Antigen (2nd exposure) Active Cytotoxic T cells + Memory Cytotoxic T cells Defend against intracellular pathogens

Antigen- presenting cell Peptide antigen Bacterium Fig. 43-17 Antigen- presenting cell Peptide antigen Bacterium Class II MHC molecule CD4 TCR (T cell receptor) Helper T cell Cytokines + Humoral immunity (secretion of antibodies by plasma cells) + Cell-mediated immunity (attack on infected cells) + + B cell Cytotoxic T cell

Cytotoxic T cell Perforin Granzymes CD8 TCR Class I MHC molecule Fig. 43-18-1 Cytotoxic T cell Perforin Granzymes CD8 TCR Class I MHC molecule Target cell Peptide antigen

Cytotoxic T cell Perforin Granzymes CD8 TCR Class I MHC molecule Pore Fig. 43-18-2 Cytotoxic T cell Perforin Granzymes CD8 TCR Class I MHC molecule Pore Target cell Peptide antigen

Released cytotoxic T cell Fig. 43-18-3 Released cytotoxic T cell Cytotoxic T cell Perforin Granzymes CD8 TCR Dying target cell Class I MHC molecule Pore Target cell Peptide antigen

Antigen-presenting cell Bacterium Fig. 43-19 Antigen-presenting cell Bacterium Peptide antigen B cell Class II MHC molecule + Clone of plasma cells Secreted antibody molecules TCR CD4 Cytokines Endoplasmic reticulum of plasma cell Activated helper T cell Helper T cell Clone of memory B cells 2 µm

Antigen-presenting cell Bacterium Fig. 43-19-1 Antigen-presenting cell Bacterium Peptide antigen Class II MHC molecule TCR CD4 Helper T cell

Antigen-presenting cell Bacterium Fig. 43-19-2 Antigen-presenting cell Bacterium Peptide antigen B cell Class II MHC molecule + TCR CD4 Cytokines Activated helper T cell Helper T cell

Antigen-presenting cell Bacterium Fig. 43-19-3 Antigen-presenting cell Bacterium Peptide antigen B cell Class II MHC molecule + Clone of plasma cells Secreted antibody molecules TCR CD4 Cytokines Activated helper T cell Helper T cell Clone of memory B cells

Fig. 43-19a Endoplasmic reticulum of plasma cell 2 µm

Fig. 43-20 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 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

Class of Immuno- globulin (Antibody) IgM (pentamer) Fig. 43-20a 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

Class of Immuno- globulin (Antibody) IgG (monomer) Fig. 43-20b Class of Immuno- globulin (Antibody) Distribution Function 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

Class of Immuno- globulin (Antibody) IgA (dimer) Fig. 43-20c Class of Immuno- globulin (Antibody) Distribution Function 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

Class of Immuno- globulin (Antibody) IgE (monomer) Fig. 43-20d Class of Immuno- globulin (Antibody) Distribution Function 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

Class of Immuno- globulin (Antibody) IgD (monomer) Fig. 43-20e Class of Immuno- globulin (Antibody) Distribution Function 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

Fig. 43-21 Viral neutralization Opsonization Activation of complement system and pore formation Bacterium Complement proteins Virus Formation of membrane attack complex Flow of water and ions Macrophage Pore Foreign cell

Fig. 43-21a Viral neutralization Virus

Fig. 43-21b Opsonization Bacterium Macrophage

Activation of complement system and pore formation Fig. 43-21c Activation of complement system and pore formation Complement proteins Formation of membrane attack complex Flow of water and ions Pore Foreign cell

Fig. 43-22

Fig. 43-23 IgE Histamine Allergen Granule Mast cell

Fig. 43-24

1.5 Antibodies to variant 1 appear Antibodies to variant 2 appear Fig. 43-25 1.5 Antibodies to variant 1 appear Antibodies to variant 2 appear Antibodies to variant 3 appear 1.0 Variant 1 Variant 2 Variant 3 Millions of parasites per mL of blood 0.5 25 26 27 28 Weeks after infection

Helper T cell concentration Fig. 43-26 Latency AIDS Relative antibody concentration 800 Relative HIV concentration 600 Helper T cell concentration in blood (cells/mm3) Helper T cell concentration 400 200 1 2 3 4 5 6 7 8 9 10 Years after untreated infection

Cell division and gene rearrangement Fig. 43-UN1 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

Fig. 43-UN2