Chapter 16

1. Chapter 16 Adaptive Immunity

2. 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 © 2012 Pearson Education Inc.

3. 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 Humoral immune responses Cell-mediated immune responses © 2012 Pearson Education Inc.

4. Lymphocyte Red blood cell Figure 16.1 A resting lymphocyte

5. Overview of Adaptive Immunity ANIMATION Humoral Immunity: Overview ANIMATION Cell-Mediated Immunity: Overview © 2012 Pearson Education Inc.

6. Elements of Adaptive Immunity The Tissues and Organs of the Lymphatic System Screen the tissues of the body for foreign antigens Composed of lymphatic vessels and lymphatic cells, tissues, and organs © 2012 Pearson Education Inc.

7. Elements of Adaptive Immunity The Tissues and Organs of the Lymphatic System Lymphatic vessels and the flow of lymph Conducts lymph from tissues and returns it to the circulatory system Lymph Liquid with similar composition to blood plasma Arises from fluid leaked from blood vessels into surrounding tissues © 2012 Pearson Education Inc.

8. Figure 16.2 The lymphatic system-overview

9. 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 lymphatic tissue (MALT) © 2012 Pearson Education Inc.

10. Elements of Adaptive Immunity Antigens Properties of antigens Molecules the body recognizes as foreign and worthy of attack Recognized by three-dimensional regions called epitopes Include various bacterial components as well as proteins of viruses, fungi, and protozoa Food and dust can also contain antigenic particles © 2012 Pearson Education Inc.

11. Figure 16.3a Antigens: epitopes (antigenic determinants) Epitopes(antigenicdeterminants) Cytoplasmicmembrane Nucleus Cytoplasm Antigen Epitopes (antigenic determinants)

12. Figure 16.3b Antigens: exogenous antigens Extracellularmicrobes Exogenousantigens Exogenous antigens

13. Figure 16.3c Antigens: endogenous antigens Endogenousantigens Intracellularvirus Virallyinfectedcell Endogenous antigens

14. Figure 16.3d Antigens: autoantigens Autoantigens(normal cell antigens) Normal(uninfected)cell Autoantigens

15. Elements of Adaptive Immunity B Lymphocytes (B Cells) and Antibodies Arise and mature in the red bone marrow Found primarily in the spleen, lymph nodes, and MALT Small percentage of B cells circulates in the blood Major function is the secretion of antibodies © 2012 Pearson Education Inc.

16. 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 Each B cell generates a single BCR Two variable regions of the BCR form the antigen-binding sites Each BCR recognizes only one epitope Individual’s repertoire of BCRs is capable of recognizing millions of different epitopes © 2012 Pearson Education Inc.

17. Epitope Figure 16.4 B cell receptor (BCR) Antigen-bindingsites Heavy chain Variable region Light chain Cytoplasmicmembrane ofB lymphocyte Transmembraneportion of BCR B cell receptor(BCR) Cytoplasm

18. 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 Identical antigen-binding sites and antigen specificity as the BCR of the activated B cell © 2012 Pearson Education Inc.

19. Figure 16.5 Basic antibody structure-overview

20. 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) © 2012 Pearson Education Inc.

21. Figure 16.6 Five functions of antibodies-overview

22. Elements of Adaptive Immunity ANIMATION Humoral Immunity: Antibody Function © 2012 Pearson Education Inc.

23. Elements of Adaptive Immunity B Lymphocytes (B Cells) and Antibodies Classes of antibodies Threats confronting the immune system are variable Class involved in the immune response depends on the type of antigen, portal of entry, and antibody function needed Five different classes of antibodies © 2012 Pearson Education Inc.

24. 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 © 2012 Pearson Education Inc.

25. Elements of Adaptive Immunity T Lymphocytes (T Cells) Produced in the red bone marrow and mature in the thymus Circulate in the lymph and blood and migrate to the lymph nodes, spleen, and Peyer’s patches Antigen-binding sites are complementary to epitopes Have T cell receptors (TCRs) on their cytoplasmic membrane © 2012 Pearson Education Inc.

26. Elements of Adaptive Immunity T Lymphocytes Specificity of the T cell receptor (TCR) TCRs do not recognize epitopes directly TCRs only bind epitopes associated with a MHC protein TCRs act primarily against cells that harbor intracellular pathogens © 2012 Pearson Education Inc.

27. Antigen-bindingsite (groove) Carbohydrate Figure 16.7 A T cell receptor (TCR) Variableregions Disulfidebond Constantregions Cytoplasmicmembraneof T cell T cell receptor(TCR) Cytoplasm

28. Elements of Adaptive Immunity T Lymphocytes Types of T lymphocytes Based on surface glycoproteins and characteristic functions Three types Cytotoxic T lymphocyte Directly kills other cells Helper T lymphocyte Helps regulate the activities of B cells and cytotoxic T cells Regulatory T lymphocyte Represses adaptive immune responses © 2012 Pearson Education Inc.

29. Elements of Adaptive Immunity ANIMATION Cell-Mediated Immunity: Cytotoxic T Cells © 2012 Pearson Education Inc.

30. Elements of Adaptive Immunity ANIMATION Cell-Mediated Immunity: Helper T Cells © 2012 Pearson Education Inc.

31. Elements of Adaptive Immunity Clonal Deletion Vital that immune responses not be directed against autoantigens Body eliminates self-reactive lymphocytes Lymphocytes that react to autoantigens undergo apoptosis © 2012 Pearson Education Inc.

32. Stem cell(in red bone marrow) Figure 16.8 Clonal deletion of T cells T cells TCRs MHC I Epitope RecognizeMHC I? Thymuscells Thymuscells Yes No Receive survivalsignal RecognizeMHC-autoantigen? Yes No Apoptosis Few Most Apoptosis Repertoire ofimmature Tc cells RegulartoyT cell (Tr)

33. Stem cell(in red bone marrow) Figure 16.9 Clonal deletion of B cells B cells BCRs Cell with autoantigens Cell with autoantigens Apoptosis To spleen Blood vessel

34. Elements of Adaptive Immunity Immune Response Cytokines Soluble regulatory proteins that act as intercellular signals Cytokines secreted by various leukocytes Cytokine network The complex web of signals among all the cells of the immune system © 2012 Pearson Education Inc.

35. Elements of Adaptive Immunity Immune System Cytokines Interleukins (ILs) Signal among leukocytes 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 © 2012 Pearson Education Inc.

36. Preparation for an Adaptive Immune Response The Roles of the Major Histocompatibility Complex 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 © 2012 Pearson Education Inc.

37. Preparation for an Adaptive Immune Response The Roles of the Major Histocompatibility Complex Antigens bind in the antigen-binding groove of MHC molecules Two classes of MHC proteins MHC class I MHC class II © 2012 Pearson Education Inc.

38. Antigen-binding grooves Figure 16.10 The two classes of major histocompatibility complex (MHC) proteins Cytoplasmicmembrane Class I MHCon every nucleatedcell Class II MHCon B cell or otherantigen-presentingcell (APC) Cytoplasm

39. Dendrites Figure 16.11 Dendritic cells

40. Preparation for an Adaptive Immune Response Antigen Processing Antigens processed for MHC proteins to display epitopes Different processes for endogenous and exogenous antigens © 2012 Pearson Education Inc.

41. Preparation for an Adaptive Immune Response ANIMATION Antigen Processing and Presentation: Overview © 2012 Pearson Education Inc.

42. Figure 16.12 The processing of T-dependent endogenous antigens Polypeptide Epitopes MHC I proteinin membraneof endoplasmicreticulum Lumen ofendoplasmicreticulum The polypeptide is catabolized to yield epitopes, whichare loaded onto complementary MHC I proteins in the ER. MHC I protein–epitope complex MHC I protein–epitopecomplexes are packaged in vesicle. Vesicle fuses with cytoplasmic membrane. MHC I protein–epitopecomplexes oncell surface Cytoplasmicmembrane MHC I protein–epitope complexes displayed oncytoplasmic membranes of all nucleated cells

43. Phagocytosisby APC Exogenouspathogenwith antigens Figure 16.13 The processing of T-dependent exogenous antigens MHC II protein inmembrane of vesicle Epitopes inphagolysosome MHC II protein–epitope complex Vesicles fuse and epitopes bind tocomplementary HHC II molecules. Vesicle fuses with cytoplasmic membrane. MHC II protein–epitope complexex oncell surface Cytoplasmicmembrane MHC II protein–epitope complexes displayed oncytoplasmic membranes of antigen-presenting cell

44. Preparation for an Adaptive Immune Response ANIMATION Antigen Processing and Presentation: Steps © 2012 Pearson Education Inc.

45. Preparation for an Adaptive Immune Response ANIMATION Antigen Processing and Presentation: MHC © 2012 Pearson Education Inc.

46. Cell-Mediated Immune Responses Respond to intracellular pathogens and abnormal body cells The most common intracellular pathogens are viruses The response is also effective against cancer cells, intracellular protozoa, and intracellular bacteria © 2012 Pearson Education Inc.

47. Cell-Mediated Immune Responses Activation of T Cell Clones and Their Functions Steps involved in activation of cytotoxic T cells Antigen presentation Helper T cell differentiation Clonal expansion Self-stimulation © 2012 Pearson Education Inc.

48. Dendritic cell Antigen presentation MHC I Figure 16.14 Activation of a clone of cytotoxic T (Tc) cells Epitope CD8 DC MHC II protein TCR Epitope TCR Tc cell InactiveTc cell Thcell IL-12 Immunological synapse IL-2 receptor(IL-2R) Th differentiation IL-2 Th1 cell Clonal expansion MemoryT cell ActiveTc cells IL-2R Self-stimulation IL-2 IL-2 Active Tc cells IL-2R IL-2

49. Figure 16.15a A cell-mediated immune response: binding of virus-infected cell Activecytotoxic T(Tc) cell TCR CD8 Viral epitope MHC Iprotein Virallyinfected cell Intracellularvirus

50. Figure 16.15b A cell-mediated immune response: perforin-granzyme cytotoxic pathway Tc cell Perforin Granzyme Perforincomplex (pore) Granzymes activateapoptotic enzymes Inactiveapoptoticenzymes Active apoptoticenzymes induceapoptosis Virally infected cell