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Adaptive Immunity

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  1. Adaptive Immunity Chapter 7

  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 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. 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

  6. 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

  7. Antigens • Immunogens vs. antigens • Antigenic determinant (epitope) • Self-antigen • Tolerance • Central and peripheral tolerance • Molecular size • Haptens • Allergens

  8. Antigen Presentation • Antigen-presenting cells (APCs) • Major histocompatibility complex (MHC) • Glycoproteins on the surface of all human cells (except RBCs) • Also referred to as human leukocyte antigens (HLAs) • MHC class I molecules • A, B, and C • MHC class II molecules • DR, DP, and DQ • MHC class III molecules

  9. Antigen Presentation

  10. Transplantation • Cells in transplanted tissue from one individual will have a different set of MHC surface antigens than those of the recipient • Therefore, a recipient can mount an immune response against the foreign MHC molecules • Haplotype • Combination of A, B, C, DR, DQ, and DP alleles

  11. Transplantation

  12. CD1 • Antigen-presenting molecules • Found on antigen-presenting and thymus cells • Present lipid antigens

  13. Antigen Recognition • Antigen is directly recognized by circulating antibody, antigen receptors on B cells (BCR), and T lymphocytes (TCR)

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

  15. Antibodies

  16. Antibodies

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

  18. 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

  19. 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

  20. 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

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

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

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

  24. 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 • Antibody valence • IgG, IgD, and IgE—2 • IgA—4 • IgM—theoretically 10, likely 5

  25. 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

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

  27. 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

  28. 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 • Final products • Plasma cells that produce antibody, effector cells that help Th, Tc, or Treg, and memory B and T cells

  29. 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 • T cells are released into the blood and take up residence in the secondary lymph organs

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

  31. Antigen Processing and Presentation

  32. Antigen Processing and Presentation

  33. Helper T Lymphocytes • “Help” the antigen-driven maturation of B and T cells • Facilitate and magnify the interaction between APCs and immunocompetent lymphocytes • Steps • Th interacts through antigen-specific and antigen-independent mechanisms • Undergoes differentiation • Mature Th interacts with plasma or T-effector cells

  34. Antigen Processing and Presentation

  35. Helper T Lymphocytes • Subsets • Th1 cells provide help in developing cell-mediated immunity • Th2 cells provide help in developing humoral immunity • Differences based on cytokine production

  36. B Cell Activation • When an immunocompetent B cell encounters an antigen for the first time, B cells with specific BCRs are stimulated to differentiate and proliferate • A differentiated B cell becomes a plasma cell • A plasma cell is a factory for antibody production • Single class or subclass of antibody

  37. 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

  38. Primary and Secondary Responses • Secondary response • More rapid • Larger amounts of antibody are produced • Rapidity is due to 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

  39. 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

  40. B Cell Clonal Selection

  41. 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

  42. T Cell Activation

  43. 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 • SAGs induce an excessive production of cytokines • Causes fever, low blood pressure, fever, and potentially shock

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

  45. 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 present

  46. Secretory (Mucosal) Immune System

  47. 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

  48. IgE Function

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

  50. Cell-Killing Mechanisms