1. Adaptive Immunity Chapter 6

2. Adaptive Immunity Antigens Specificity Memory Antibodies Lymphocytes

3. Adaptive Immunity Clonal diversity –Production of T- and B-lymphocytes –Antigen recognition –Lymphocyte specificity Clonal selection –Antigen processing –Cellular interaction

4. Humoral(blood) and Cell-Mediated Immunity The cellular and humoral responses are not independent Humoral immunity –“Fluid” immunity –Circulating antibody Cell-mediated immunity –T cell differentiation

5. I Immune Response Humoral Immunity Cell-mediated Immunity (Antibody)(Cytotoxicity) B cells T cells

6. Active vs. Passive Immunity Active immunity –Antibodies or T cells produced after either a natural exposure to an antigen or after immunization Passive immunity –Preformed antibodies or T-lymphocytes are transferred from a donor to a recipient

8. Recognition and Response Required for a successful immune response Clusters of differentiation (CD) –Originally used to describe proteins found on the surface of lymphocytes –Now it is a labeling system used to identify a family of proteins on many cells

9. Each antibody binds to a specific antigen; an interaction similar to a lock and key

10. Antigens Immunogens vs. antigens Antigenic determinant (epitope) Antigenic binding site (paratope) Immunogenic criteria

11. Antigens Self-antigen Molecular size –Haptens - Allergens Chemical Complexity Sufficient Quantity Mosby items and derived items © 2008 by Mosby, Inc., an affiliate of Elsevier Inc.

12. Antibodies Also called immunoglobulins Produced by plasma cells Classes of antibody –IgG, IgA, IgM, IgE, and IgD Characterized by antigenic, structural, and functional differences

13. Immunoglobulin G (IgG) Most abundant class (80%-85%) Transported across the placenta Four classes –IgG1, IgG2, IgG3, and IgG4

14. Immunoglobulin A (IgA) Two classes –IgA1 molecules are found predominantly in the blood –IgA2 molecules are found predominantly in normal body secretions IgAs found in body secretions are dimers anchored by a J chain and a “secretory” piece –Secretory piece may function to protect IgAs against enzyme degradation

15. Immunoglobulin M (IgM) Largest of the immunoglobulins Pentamer stabilized by a J chain First antibody produced during the primary response to an antigen Synthesized during fetal life

16. Immunoglobulin D (IgD) Limited information on IgD function Low concentration in the blood Located primarily on the surface of developing B-lymphocytes Function as one type of B cell antigen receptor activation of basophills

17. Immunoglobulin E (IgE) Least concentrated of the immunoglobulin classes in the circulation Mediator of many common allergic responses Defender against parasites

18. Antibody Structure Antigen-binding fragment (Fab) –Recognition sites (receptors) for antigenic determinants Crystalline fragment (Fc) –Responsible for biologic function Polypeptide chains (4) –Light chains (2) and heavy chains (2)

19. Antibody Structure Hinge region Constant and variable regions –Complementary determining regions (CDRs) –Framework regions (FRs)

20. Antigen Binding Amino acid sequences of the variable regions of the heavy and light chains Framework regions control antibody folding Lock and key –Noncovalent chemical interactions

23. Antigen Binding Antibody valence –IgG, IgD, and IgE—2 –IgA—4 –IgM—theoretically 10, likely 5

24. B Cell–Receptor Complex Located on surface of B cells Consists of: –Antigen-recognition molecules Monomer IgM and IgD –Accessory intracellular-signaling molecules Ig-alpha and Ig-beta heterodimers

25. Cell mediated response T cells Lymphokine producing cells(CYTOKINES) T cell response KILLS IMMEDIATLEY.

26. T Cell–Receptor Complex Antibody-like transmembrane protein (TCR) Accessory proteins for intracellular signaling –Referred to as CD3

28. Time course of immune response

29. Generation of Clonal Diversity All necessary receptor specificities are produced Takes place in the primary (central) lymphoid organs Results in immature but immunocompetent T and B cells Primarily occurs in the fetus

30. Clonal Selection Immunocompetent T and B cells migrate from the primary lymphoid organs to the secondary lymphoid organs to await antigen Primarily after birth Clonal selection is initiated by antigen

31. Clonal Selection Final products –Plasma cells that produce antibody, effector cells that help Th(helper), Tc (kills), or Treg (regulates), and memory B and T cells

32. T Cell Maturation The thymus is the central lymphoid organ of T cell development T cells move from the thymic cortex to the medulla Changes –Development of the T cell receptors and expression of surface molecules

33. T Cell Maturation T cells are released into the blood and take up residence in the secondary lymph organs

34. Antigen Processing and Presentation Antigens require processing and presentation by antigen-presenting cells (APCs) –Dendritic cells, macrophages, and B- lymphocytes

35. Antigen Processing and Presentation For processing and presentation to occur, the antigen must be of the appropriate type, the lymphocytes must be prepared to recognize the presented antigen, and the antigen must be presented appropriately

36. Antigen Processing and Presentation

37. Helper T-Lymphocytes “Help” the antigen-driven maturation of B and T cells Facilitate and magnify the interaction between APCs and immunocompetent lymphocytes

38. Helper T-Lymphocytes Steps –Th interacts through antigen-specific and antigen-independent mechanisms –Undergoes differentiation –Mature Th interacts with plasma or T- effector cells

39. Antigen Processing and Presentation

40. Helper T-Lymphocytes express a CD4 protein on surface assist leukocyte CD8 are in killer cells Subsets –Th1 cells provide help in developing cell- mediated immunity –Th2 cells provide help in developing humoral immunity –Differences based on cytokine production

41. B Cell Activation When an immunocompetent B cell encounters an antigen for the first time, B cells with specific BCRs(binding receptors IgM, IgD) are stimulated to differentiate and proliferate A differentiated B cell becomes a plasma cell A plasma cell is a factory for antibody production

43. Primary and Secondary Responses Primary response –Initial exposure –Latent period or lag phase B cell differentiation is occurring –After 5 to 7 days, an IgM antibody for a specific antigen is detected –An IgG response equal or slightly less follows the IgM response

44. Primary and Secondary Responses Secondary response –More rapid –Larger amounts of antibody are produced –Rapidity is caused by the presence of memory cells that do not have to differentiate –IgM is produced in similar quantities to the primary response, but IgG is produced in considerably greater numbers

45. Class Switch Immunocompetent B cells use IgM and IgD as receptors During clonal selection, B cells have the option of changing the class of the antibody –One of four IgGs, one of two IgAs, IgE, or an IgM in a pentamer form –DNA rearrangement

46. B Cell Clonal Selection

47. T Cell Activation Binding antigen to specific T cell receptors Allows: –Direct killing of foreign or abnormal cells –Assistance or activation of other cells T regulatory cells (Treg) –Regulate the immune response to avoid attacking “self” Memory T cells

48. Superantigens (SAGs) Bind the variable portion of the TCR and the MHC class II molecules outside of their antigen-presentation sites Activates a large population of T- lymphocytes regardless of antigen specificity

49. Superantigens (SAGs) SAGs induce an excessive production of cytokines –Causes fever, low blood pressure, and potentially shock

50. Antibody Function Direct –Neutralization –Agglutination –Precipitation Indirect –Opsonization Degree of antibody protection is assessed by an antibody titer

51. Secretory (Mucosal) Immune System Lymphoid tissues that protect the external surfaces of the body Antibodies present in tears, sweat, saliva, mucus, and breast milk IgA is the dominant immunoglobulin –Small numbers of IgG and IgM are presents

52. Secretory (Mucosal) Immune System

53. IgE Function Provides protection from large parasites –Initiates an inflammatory reaction to attract eosinophils When produced against innocuous environmental antigens, they are a common cause of allergies –Fc portions of IgEs are bound to mast cells

54. IgE Function

55. Cell-Killing Mechanisms Cytotoxic T-lymphocytes –Destroy cancer cells or cells infected with virus –Perforin, granzymes, or direct receptor interactions

56. Cell-Killing Mechanisms

57. Other Cells Natural killer (NK) cells –Complement Tc cell mechanisms Regulatory T cells (Treg) –Provide peripheral tolerance –Affect recognition of antigen and suppress proliferative steps of antigen recognition

58. Fetal and Neonatal Immunity Antibody function is deficient –Capable of primary IgM response; unable to produce an IgG challenge Immunity provided by maternal antibody –Trophoblastic cells transport maternal IgG across the placenta –Newborn IgG levels are near adult levels

59. Fetal and Neonatal Immunity

60. Aging and Immune Function Decreased T cell activity –Thymic size is 15% of its maximum size Decreased production of specific antibodies Increase in circulating antigen- antibody complexes Increase in circulating autoantibodies Decrease in circulating memory B cells

61. 1.Which of the following best describes foreign or nonself substances? A.Immunoglobulins B.Lymphocytes C.Antibodies D.Antigens Elsevier items and derived items © 2008 by Mosby, Inc., an affiliate of Elsevier Inc. Some material was previously published.

62. 2.Which of the following terms describes the type of immunity that occurs when preformed antibodies transfer from donor to recipient? A.Passive immunity B.Active immunity C.Memory immunity D.Cellular immunity Elsevier items and derived items © 2008 by Mosby, Inc., an affiliate of Elsevier Inc. Some material was previously published.

63. Chapter 6 The End Mosby items and derived items © 2008 by Mosby, Inc., an affiliate of Elsevier Inc.