Acquired Immunity: Lymphocytes in Specific Defense

1. Chapter 43 The Immune System

2. Concept 43.2: In acquired immunity, lymphocytes provide specific defenses against infection • Acquired immunity is the body’s second major kind of defense • An antigen is a foreign molecule that is recognized by lymphocytes and elicits a response from them • A lymphocyte recognizes and binds to a small portion of the antigen called an epitope

3. Acquired Immunity: occurs when the body adapts to specific infections; it’s like the body learns about the “invader” and kills it as effectively as possible.

4. Antigen- binding sites Epitopes (antigenic determinants) Recognition sites for an antibody LE 43-7 Antibody A Antigen Antibody B Antibody C

5. Antigen Recognition by Lymphocytes • Two main types of lymphocytes circulate in the blood of vertebrates: B lymphocytes (B cells) and T lymphocytes (T cells) • A single B cell or T cell has about 100,000 identical antigen receptors • All antigen receptors on a single cell recognize the same epitope

6. B Cell Receptors for Antigens • B cell receptors bind to specific, intact antigens • Secreted antibodies, or immunoglobulins, are structurally similar to B cell receptors but lack transmembrane regions that anchor receptors in the plasma membrane

7. Antigen- binding site Antigen- binding site Disulfide bridge V V V V Light chain Variable regions C C C C Constant regions Transmembrane region Plasma membrane Heavy chains B cell Cytoplasm of B cell A B cell receptor consists of two identical heavy chains and two identical light chains linked by several disulfide bridges.

8. T Cell Receptors for Antigens and the Role of the MHC Antigen- binding site • Each T cell receptor consists of two different polypeptide chains Variable regions V V C C Constant regions Transmembrane region Plasma membrane b chain  chain Disulfide bridge T cell Cytoplasm of T cell A T cell receptor consists of one a chain and one b chain linked by a disulfide bridge.

9. T cells bind to antigen fragments that are bound to cell-surface proteins called MHC molecules • MHC molecules are so named because they are encoded by a family of genes called the major histocompatibility complex • Serve to distinguish one individual from another  recognition of “self” and “non-self”

10. Infected cells produce MHC molecules, which bind to antigen fragments and are transported to the cell surface, a process called antigen presentation • A nearby T cell can then detect the antigen fragment displayed on the cell’s surface • Depending on their source, peptide antigens are handled by different classes of MHC molecules

11. Class I MHC molecules are found on almost all nucleated cells of the body • They display peptide antigens to cytotoxic T cells

12. Class II MHC molecules are located mainly on dendritic cells, macrophages, and B cells • They display antigens to helper T cells

13. Infected cell Microbe Antigen- presenting cell Antigen fragment Antigen fragment LE 43-9 Class II MHC molecule Class I MHC molecule T cell receptor T cell receptor Cytotoxic T cell Helper T cell

14. Clonal Selection of Lymphocytes • In a primary immune response, binding of antigen to a mature lymphocyte induces the lymphocyte’s proliferation and differentiation • This process is called clonal selection • Clonal selection of B cells generates a clone of short-lived activated effector cells and a clone of long-lived memory cells

15. Antigen molecules B cells that differ in antigen specificity Antigen receptor Antibody molecules Clone of plasma cells Clone of memory cells

17. In the secondary immune response, memory cells facilitate a faster, more efficient response Second exposure to antigen X (secondary response) 104 First exposure to antigen X (primary response) 103 Antibodies to antigen X Antibody concentration (arbitrary units) 102 Antibodies to antigen Z 101 100 21 7 0 28 49 14 35 56 42 Time (days)

18. Concept 43.3: Humoral and cell-mediated immunity defend against different types of threats • Humoral immune response involves activation and clonal selection of B cells, resulting in production of secreted antibodies • Cell-mediated immune response involves activation and clonal selection of cytotoxic T cells

19. Cell-mediated immune response Humoral immune response First exposure to antigen Antigens displayed by infected cells Antigens engulfed and displayed by dendritic cells Intact antigens Activate Activate Activate Secreted cytokines activate B cells Cytotoxic T cell Helper T cell Gives rise to Gives rise to Gives rise to Active and memory helper T cells Memory cytotoxic T cells Active cytotoxic T cells Plasma cells Memory B cells Defend against infected cells, cancer cells, and transplanted tissues Secrete antibodies that defend against pathogens and toxins in extracellular fluid

20. Helper T Cells: A Response to Nearly All Antigens • A surface protein called CD4 binds the class II MHC molecule • This binding keeps the helper T cell joined to the antigen-presenting cell while activation occurs • Activated helper T cells secrete cytokines that stimulate other lymphocytes

21. Peptide antigen Cytotoxic T cell Dendritic cell Class II MHC molecule Cell-mediated immunity (attack on infected cells) Helper T cell Bacterium TCR Humoral immunity (secretion of antibodies by plasma cells) CD4 Dendritic cell B cell Cytokines

23. Cytotoxic T Cells: A Response to Infected Cells and Cancer Cells • Cytotoxic T cells make CD8, a surface protein that greatly enhances interaction between a target cell and a cytotoxic T cell • Binding to a class I MHC complex on an infected cell activates a cytotoxic T cell and makes it an active killer • The activated cytotoxic T cell secretes proteins that destroy the infected target cell

24. Released cytotoxic T cell Cytotoxic T cell Perforin Cancer cell Granzymes TCR Apoptotic target cell CD8 Class I MHC molecule Pore Target cell Peptide antigen Cytotoxic T cell

26. Macrophage Bacterium Peptide antigen LE 43-17 B cell Class II MHC molecule Secreted antibody molecules Clone of plasma cells TCR CD4 Endoplasmic reticulum of plasma cell + Cytokines Helper T cell Activated helper T cell Clone of memory B cells