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1. 21 The Immune System: Innate and Adaptive Body Defenses: Part B

2. Humoral Immunity ActivityB-cellsAntibodies

3. Antibodies • Immunoglobulins—gamma globulin portion of blood • Proteins secreted by plasma cells • Capable of binding specifically with antigen detected by B cells

4. Basic Antibody Structure • T-or Y-shaped monomer of four looping linked polypeptide chains • Two identical heavy (H) chains and two identical light (L) chains • Variable (V) regions of each arm combine to form two identical antigen-binding sites

5. Basic Antibody Structure • Constant (C) region of stem determines • The antibody class (IgM, IgA, IgD, IgG, or IgE) • The cells and chemicals that the antibody can bind to • How the antibody class functions in antigen elimination

6. Antigen-binding site Heavy chain variable region Hinge region Heavy chain constant region Stem region Light chain variable region Light chain constant region Disulfide bond (a) Figure 21.14a

7. Classes of Antibodies • IgM • A pentamer; first antibody released • Potent agglutinating agent • Readily fixes and activates complement • IgA (secretory IgA) • Monomer or dimer; in mucus and other secretions • Helps prevent entry of pathogens

8. Table 21.3

9. Classes of Antibodies • IgD • Monomer attached to the surface of B cells • Functions as a B cell receptor • IgG • Monomer; 75–85% of antibodies in plasma • From secondary and late primary responses • Crosses the placental barrier

10. Classes of Antibodies • IgE • Monomer active in some allergies and parasitic infections • Causes mast cells and basophils to release histamine

11. Table 21.3

12. Generating Antibody Diversity • Billions of antibodies result from somatic recombination of gene segments • Hypervariable regions of some genes increase antibody variation through somatic mutations • Each plasma cell can switch the type of H chain produced, making an antibody of a different class

13. Antibody Targets • Antibodies inactivate and tag antigens • Form antigen-antibody (immune) complexes • Defensive mechanisms used by antibodies • Neutralization and agglutination (the two most important) • Precipitation and complement fixation

14. Neutralization • Simplest mechanism • Antibodies block specific sites on viruses or bacterial exotoxins • Prevent these antigens from binding to receptors on tissue cells • Antigen-antibody complexes undergo phagocytosis

15. Agglutination • Antibodies bind the same determinant on more than one cell-bound antigen • Cross-linked antigen-antibody complexes agglutinate • Example: clumping of mismatched blood cells

16. Precipitation • Soluble molecules are cross-linked • Complexes precipitate and are subject to phagocytosis

17. Complement Fixation and Activation • Main antibody defense against cellular antigens (bacteria and wrong RBCs) • Several antibodies bind close together on a cellular antigen • Their complement-binding sites trigger complement fixation into the cell’s surface • Complement triggers cell lysis

18. Complement Fixation and Activation • Activated complement functions • Amplifies the inflammatory response • Opsonization • Enlists more and more defensive elements

19. Ig E can also attach to parasites causing Eosinophils to attack

20. Adaptive defenses Humoral immunity Antigen-antibody complex Antigen Antibody Inactivates by Fixes and activates Neutralization (masks dangerous parts of bacterial exotoxins; viruses) Agglutination (cell-bound antigens) Precipitation (soluble antigens) Complement Enhances Enhances Leads to Inflammation Phagocytosis Cell lysis Chemotaxis Histamine release Figure 21.15

21. Monoclonal Antibodies • Commercially prepared pure antibody • Produced by hybridomas • Cell hybrids: fusion of a tumor cell and a B cell • Proliferate indefinitely and have the ability to produce a single type of antibody • Used in research, clinical testing, and cancer treatment • Diagnose pregnancy (HCG), certain sexually transmitted diseases like AIDS (ELISA), certain cancers, hepatitis and rabies • Treat leukemias and lymphomas – cancers in the blood stream that are accessible to antibodies

22. Cell Mediated Immune Responses T-cell Activity

23. Cell-Mediated Immune Response • T cells provide defense against intracellular antigens • Two types of surface receptors of T cells • T cell antigen receptors which are CD 3 • Cell differentiation glycoproteins • CD4 or CD8, CD 10, CD gamma- delta • Play a role in T cell interactions with other cells

24. All T cells have a T cell receptor – it obtained in the thymus gland – they slightly differ in the variable region

25. Cell-Mediated Immune Response • Major types of T cells • CD4 cells become helper T cells (TH) when activated • CD8 cells become cytotoxic T cells (TC) that destroy cells harboring foreign antigens • Other types of T cells • Regulatory T cells (TREG) CD 10 • T – gamma - delta • Memory T cells

26. Adaptive defenses Cellular immunity Immature lymphocyte Red bone marrow T cell receptor T cell receptor Maturation Class I MHC protein Class II MHC protein CD4 cell CD8 cell Thymus Activation Activation APC (dendritic cell) Memory cells APC (dendritic cell) CD4 CD8 Lymphoid tissues and organs Effector cells Helper T cells (or regulatory T cells) Cytotoxic T cells Blood plasma Figure 21.16

27. Comparison of Humoral and Cell-Mediated Response • Antibodies of the humoral response • The simplest ammunition of the immune response • Targets • Bacteria and molecules in extracellular environments (body secretions, tissue fluid, blood, and lymph)

28. Comparison of Humoral and Cell-Mediated Response • T cells of the cell-mediated response • Recognize and respond only to processed fragments of antigen displayed on the surface of body cells • Targets • Body cells infected by viruses or bacteria • Abnormal or cancerous cells • Cells of infused or transplanted foreign tissue

29. Antigen Recognition • Immunocompetent T cells are activated when their surface receptors bind to a recognized antigen (nonself) • T cells must simultaneously recognize • Nonself (the antigen) • Self (an MHC protein of a body cell)

30. MHC Proteins • Two types of MHC proteins are important to T cell activation • Class I MHC proteins - displayed by all cells except RBCs • Class II MHC proteins – displayed by APCs (dendritic cells, macrophages and B cells) • Both types are synthesized at the ER and bind to peptide fragments

31. Class I MHC Proteins • Bind with fragment of a protein synthesized in the cell (endogenous antigen) • Endogenous antigen is a self-antigen in a normal cell; a nonself antigen in an infected or abnormal cell • Informs cytotoxic T cells of the presence of microorganisms hiding in cells (cytotoxic T cells ignore displayed self-antigens)

32. 8 – 9 endogenously derived Amino acids in MHC I Cytoplasm of any tissue cell Cisternae ofendoplasmicreticulum (ER) Endogenous antigenpeptides enter ER viatransport protein. 2 Endogenousantigen is degradedby protease. 1 3 Endogenousantigen peptide isloaded onto classI MHC protein. Endogenous antigen—self-protein or foreign(viral or cancer) protein 4 Loaded MHC proteinmigrates in vesicle tothe plasma membrane,where it displays theantigenic peptide. Transportprotein(ATPase) Antigenic peptide Plasma membrane of a tissue cell Extracellular fluid (a) Endogenous antigens are processed and displayed on class I MHC of all cells. MHC produced in Endoplasmic Reticulum Figure 21.17a

33. Cytoplasm of any tissue cell Endogenousantigen is degradedby protease. 1 Endogenous antigen—self-protein or foreign(viral or cancer) protein Plasma membrane of a tissue cell Extracellular fluid (a) Endogenous antigens are processed and displayed on class I MHC of all cells. Figure 21.17a, step 1

34. Cytoplasm of any tissue cell Cisternae ofendoplasmicreticulum (ER) Endogenous antigenpeptides enter ER viatransport protein. 2 Endogenousantigen is degradedby protease. 1 Endogenous antigen—self-protein or foreign(viral or cancer) protein Transportprotein(ATPase) Plasma membrane of a tissue cell Extracellular fluid (a) Endogenous antigens are processed and displayed on class I MHC of all cells. Figure 21.17a, step 2

35. Cytoplasm of any tissue cell Cisternae ofendoplasmicreticulum (ER) Endogenous antigenpeptides enter ER viatransport protein. 2 Endogenousantigen is degradedby protease. 1 Endogenousantigen peptide isloaded onto classI MHC protein. 3 Endogenous antigen—self-protein or foreign(viral or cancer) protein Transportprotein(ATPase) Plasma membrane of a tissue cell Extracellular fluid (a) Endogenous antigens are processed and displayed on class I MHC of all cells. Figure 21.17a, step 3

36. Cytoplasm of any tissue cell Cisternae ofendoplasmicreticulum (ER) Endogenous antigenpeptides enter ER viatransport protein. 2 Endogenousantigen is degradedby protease. 1 3 Endogenousantigen peptide isloaded onto classI MHC protein. Endogenous antigen—self-protein or foreign(viral or cancer) protein 4 Loaded MHC proteinmigrates in vesicle tothe plasma membrane,where it displays theantigenic peptide. Transportprotein(ATPase) Antigenic peptide Plasma membrane of a tissue cell Extracellular fluid (a) Endogenous antigens are processed and displayed on class I MHC of all cells. Figure 21.17a, step 4

37. Only Antigen Presenting Cells have MHC II • Antigen presenting cells are (1) dendritic cells (2) macrophages (3) some B-cells • Antigen presenting cells display both MHC I and MHC II • In order to present exogenous antigens on MHC II – the organism must under phagocytosis and lysis

38. Class II MHC Proteins • Bind with fragments of exogenous antigens that have been engulfed and broken down in a phagolysosome • Recognized by helper T cells

39. 14 – 17 exogenously derived amino acids displayed in MHC II Cytoplasm of APC 1a Class II MHC issynthesized in ER. Invariant chain prevents class II MHC from binding to peptides in the ER. Vesicle fuses withphagolysosome. Invariantchain is removed, andantigen is loaded. 3 2a Class II MHCis exportedfrom ER in avesicle. Cisternae ofendoplasmicreticulum (ER) Phagosome 1b Extracellularantigen (bacterium)is phagocytized. Vesicle withloaded MHCmigrates to theplasmamembrane. 4 2b Phagosome mergeswith lysosome, forminga phagolysosome;antigen is degraded. Lysosome Plasma membrane of APC Extracellularantigen Antigenic peptide Extracellular fluid (b) Exogenous antigens are processed and displayed on class II MHC ofantigen-presenting cells (APCs). Figure 21.17b

40. Cytoplasm of APC 1a Class II MHC issynthesized in ER. Invariant chain prevents class II MHC from binding to peptides in the ER. Cisternae ofendoplasmicreticulum (ER) Plasma membrane of APC Extracellular fluid (b) Exogenous antigens are processed and displayed on class II MHC ofantigen-presenting cells (APCs). Figure 21.17b, step 1a

41. Cytoplasm of APC 1a Class II MHC issynthesized in ER. Invariant chain prevents class II MHC from binding to peptides in the ER. Cisternae ofendoplasmicreticulum (ER) 1b Extracellularantigen (bacterium)is phagocytized. Plasma membrane of APC Extracellularantigen Extracellular fluid (b) Exogenous antigens are processed and displayed on class II MHC ofantigen-presenting cells (APCs). Figure 21.17b, step 1b

42. Cytoplasm of APC 1a Class II MHC issynthesized in ER. Invariant chain prevents class II MHC from binding to peptides in the ER. 2a Class II MHCis exportedfrom ER in avesicle. Cisternae ofendoplasmicreticulum (ER) 1b Extracellularantigen (bacterium)is phagocytized. Plasma membrane of APC Extracellularantigen Extracellular fluid (b) Exogenous antigens are processed and displayed on class II MHC ofantigen-presenting cells (APCs). Figure 21.17b, step 2a

43. Cytoplasm of APC 1a Class II MHC issynthesized in ER. Invariant chain prevents class II MHC from binding to peptides in the ER. 2a Class II MHCis exportedfrom ER in avesicle. Cisternae ofendoplasmicreticulum (ER) Phagosome 1b Extracellularantigen (bacterium)is phagocytized. 2b Phagosome mergeswith lysosome, forminga phagolysosome;antigen is degraded. Lysosome Plasma membrane of APC Extracellularantigen Extracellular fluid (b) Exogenous antigens are processed and displayed on class II MHC ofantigen-presenting cells (APCs). Figure 21.17b, step 2b

44. Cytoplasm of APC 1a Class II MHC issynthesized in ER. Invariant chain prevents class II MHC from binding to peptides in the ER. Vesicle fuses withphagolysosome. Invariantchain is removed, andantigen is loaded. 3 2a Class II MHCis exportedfrom ER in avesicle. Cisternae ofendoplasmicreticulum (ER) Phagosome 1b Extracellularantigen (bacterium)is phagocytized. 2b Phagosome mergeswith lysosome, forminga phagolysosome;antigen is degraded. Lysosome Plasma membrane of APC Extracellularantigen Extracellular fluid (b) Exogenous antigens are processed and displayed on class II MHC ofantigen-presenting cells (APCs). Figure 21.17b, step 3

45. Cytoplasm of APC 1a Class II MHC issynthesized in ER. Invariant chain prevents class II MHC from binding to peptides in the ER. Vesicle fuses withphagolysosome. Invariantchain is removed, andantigen is loaded. 3 2a Class II MHCis exportedfrom ER in avesicle. Cisternae ofendoplasmicreticulum (ER) Phagosome 1b Extracellularantigen (bacterium)is phagocytized. Vesicle withloaded MHCmigrates to theplasmamembrane. 4 2b Phagosome mergeswith lysosome, forminga phagolysosome;antigen is degraded. Lysosome Plasma membrane of APC Extracellularantigen Antigenic peptide Extracellular fluid (b) Exogenous antigens are processed and displayed on class II MHC ofantigen-presenting cells (APCs). Figure 21.17b, step 4

46. Some antigen presenting cells can present exogenous antigens on their MHC I so as to be seen by T – cytotoxic cells • The dendritic cell can either engulf endogenous antigens from infected cells or form temporary gap junctions to bring them in to the cell

47. T Cell Activation • APCs (most often a dendritic cell) migrate to lymph nodes and other lymphoid tissues to present their antigens to T cells • T cell activation is a two-step process • Antigen binding • Co-stimulation

48. T Cell Activation: Antigen Binding • CD4 and CD8 cells bind to different classes of MHC proteins (MHC restriction) • CD4 cells bind to antigen linked to class II MHC proteins of APCs • CD8 cells are activated by antigen fragments linked to class I MHC of APCs

49. T Cell Activation: Antigen Binding • Dendritic cells are able to obtain other cells’ endogenous antigens by • Engulfing dying virus-infected or tumor cells • Importing antigens through temporary gap junctions with infected cells • Dendritic cells then display the endogenous antigens on both class I and class II MHCs

50. T cell receptor (CD 3) A T cell receptor (TCR) is similar to surface antibodies on B-cells but instead of 4 polypeptide chains – it has two pp chains The variable portions V alpha and V beta determine the MHC (I or II) to bind to and the antigen recognition Antibody