Chapter 17, part B

1. Chapter 17, part B Specific Defenses of the Host: The Immune Response

2. The Results of Ag-Ab Binding Figure 17.9

3. Antibody titer: • Is the amount of Ab in serum Figure 17.10

4. Total Ab IgG Ab IgM Ab 2o Ag 1o Ag A b T i t e r D a y s A f t e r I m m u n i z a t i o n Anamnestic Response

5. Third graph • After the primary exposure to an antigen, there is an inductive period of generally several days to a week when no measurable antibodies are detected in the serum. This is the period when the antigen is being exposed to immunocompetent cells, being processed by APCs, clonal selection and clonal expansion are taking place, and B-lymphocytes are differentiating into plasma cells and B-memory cells. Because of the memory cells, however, a second exposure to the same antigen results in more antibodies being made faster for a longer period of time

6. Figure 17.17 The primary and secondary immune responses to an antigen. IgG IgM Second exposure to antigen Initial exposure to antigen Antibody titer in serum Time (days)

7. Monoclonal Antibodies • Hybridomas are produced by fusing a cancer cell with an Ab-secreting plasma cells • The hybridoma cell culture is immortal and produces monoclonal Abs (Mabs) • Immunotoxins: Mabs conjugated with a toxin to target cancer cells • Chimeric Mabs: Genetically modified mice that produce Ab with a human constant region • Humanized Mabs: Mabs that are mostly human, except for mouse antigen-binding

8. Monoclonal Antibodies Figure 17.11

9. Figure 18.2.1-2 The Production of Monoclonal Antibodies. Antigen A mouse is injected with a specific antigen that will induce production of antibodies against that antigen. 1 The spleen of the mouse is removed and homogenized into a cell suspension. The suspension includes B cells that produce antibodies against the injected antigen. 2 Spleen

10. Figure 18.2.3-4 The Production of Monoclonal Antibodies. Suspension of spleen cells The spleen cells are then mixed with myeloma cells that are capable of continuous growth in culture but have lost the ability to produce antibodies. Some of the antibody-producing spleen cells and myeloma cells fuse to form hybrid cells. These hybrid cells are now capable of growing continuously in culture while producing antibodies. 3 Spleen cells Myeloma cells Suspension of myeloma cells Cultured myeloma cells (cancerous B cells) Hybrid cells Hybrid cell Myeloma cell Spleen cell The mixture of cells is placed in a selective medium that allows only hybrid cells to grow. 4

11. Figure 18.2.5-6 The Production of Monoclonal Antibodies. Hybridomas Hybrid cells proliferate into clones called hybridomas. The hybridomasare screened for production of the desired antibody. 5 Desired monoclonal antibodies 6 The selected hybridomas are then cultured to produce large quantities of monoclonal antibodies. Isolated antibodies are used for treating and diagnosing disease.

12. Monoclonal Antibodies (Mabs) • Muromonab-CD3: for kidney transplant • Infliximab: for Crohn’s disease • Comalizumab: for allergic asthma • Rituximab: rheumatoid arthritis • Trastuzumab: Herceptin for breast cancer

13. Immune system cells communicate via cytokines • Interleukin-1 Stimulates TH cells • Interleukin-2 Activates TH, B, TC, and NK cells • Interleukin-12 Differentiation of CD4 cells • -Interferon Increase activity of macrophages • Chemokines Cause leukocytes to move to an infection

14. Cell-Mediated Immunity • Specialized lymphocytes, mostly T cells, respond to intracellular Ags • After differentiating in the thymus, T cells migrate to lymphoid tissue • T cells differentiate into effector T cells when stimulated by an Ag • Some effector T cells become memory cells • Effector T • TH TC TS TD

15. Table 17.2 Principal Cells That Function in Cell-Mediated Immunity

16. T Cells and Cellular Immunity • T cells respond to Ag by T-cell receptors (TCRs) • T cells require antigen-presenting cells (APCs) • Pathogens entering the gastrointestinal or respiratory tracts pass through: • M (microfold) cells over • Peyer’s patches, which contain APCs

17. (a) M cell on Peyer’s patch. Note the tips of the closely packed microvilli on the surrounding epithelial cells. (b) M cells facilitate contact between the antigens passing through the intestinal tract and cells of the body’s immune system. Figure 17.9 M cells. Microvilli on epithelial cell Antigen M cell TH cell Pocket B cells Macrophage Epithelial cell

18. T lympocytes T lymphocytes are matured under influence of the thymus gland Mature into different types: • Helper T Cells (CD4, TH) • Activate cells related to cell-mediated immunity • Activate B cells to produce eosinophils, IgM, and IgE • Cytotoxic T Cells (CD8, TC) • Destroy target cells with perforin

19. Figure 17.11 Lineage of effector T helper cell classes and pathogens targeted. Antibodies TH1 cells B cell TH2 cells TH17 cells Cell-mediated immunity; control of intracellular pathogens, delayed hypersensitivity reactions (page 535); stimulates macrophages. Recruits neutrophils; provides protection against extracellular bacteria and fungi TH cell IL-17 IFN-g TH17 cells TH1 cells IL-4 TH2 cells Fungi Extracellular bacteria Neutrophil Macrophage Intracellular bacteria and protozoa Mast cell Basophil Eosinophil Important in allergic responses, especially by production of IgE Stimulates activity of eosinophils to control extracellular parasites such as helminths (see ADCC, page 495). Helminth

20. T Lymphocytes • Delayed Hypersensitivity T Cells (TD) • Associated with allergic reaction, transplant rejection, and tuberculin skin test • Suppressor T cells (TS) • Turn off immune response when Ag no longer present

21. Helper T Cells Figure 17.13

22. Figure 17.10 Activation of CD4+T helper cells. An APC encounters and ingests a microorganism. The antigen is enzymatically processed into short peptides, which combine with MHC class II molecules and are displayed on the surface of the APC. A receptor (TCR) on the surface of the CD4+T helper cell (TH cell) binds to the MHC–antigen complex. If this includes a Toll-like receptor, the APC is stimulated to secrete a costimulatory molecule. These two signals activate the TH cell, which produces cytokines. TH cell receptor (TCR) The cytokines cause the TH cell (which recognizes a dendritic cell that is producing costimulatory molecules) to become activated. APC (dendritic cell) T helper cell Antigen Complex of MHC class II molecule and antigen fragment Cytokines Antigen fragment (short peptides) Microorganism carrying antigens Costimulatory molecule, (required to activate T cells that have not previously encountered antigen)

23. Cytotoxic T Cells and Cell-mediated Cytotoxicity Figure 17.14

24. T Cytotoxic Cells • CD8+or TC cells • Target cells are self-cells carrying endogenous antigens • Activated into cytotoxic T lymphocytes (CTLs) • CTLs recognize Ag + MHC I • Induce apoptosis in target cell • CTL releases perforin and granzymes

25. Figure 17.12 Killing of virus-infected target cell by cytotoxic T lymphocyte. Processed antigen presented with MHC class I T cell receptors Infected target cell is lysed MHC class I Processed antigen CTL Virus-infected cell (example of endogenous antigen) Virus-infected cell Cytotoxic T lymphocyte (CTL) A normal cell will not trigger a response by a cytotoxic T lymphocyte (CTL), but a virus-infected cell (shown here) or a cancer cell produces abnormal endogenous antigens. The abnormal antigen is presented on the cell surface in association with MHC class I molecules. CD8+T cells with receptors for the antigen are transformed into CTLs. The CTL induces destruction of the virus-infected cell by apoptosis.

26. Nonspecific Cells • Activated macrophages: Macrophages stimulated by ingesting Ag or by cytokines • Natural killer cells: Lymphocytes that destroy virus-infected cells, tumor Figure 17.15

27. T-independent Antigens B cell Figure 17.17

28. T-Dependent Antigens Figure 17.16

29. Dendritic cells present antigens

30. Antibody-Dependent Cell-Mediated Cytotoxicity Figure 17.18

31. T-dependent and independent antigens