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Humoral Immunity Graphics are used with permission of Pearson Education Inc., publishing as Benjamin Cummings (http://www.aw-bc.com). Page 1: Introduction Host defense mechanisms in which antibody plays a role are referred to as humoral immunity. B cells proliferate and differentiate into clones of antibody-secreting plasma cells following activation. Each plasma cell secretes thousands of antibody molecules, each with the same unique antigen-binding specificity as the parental B cell. Antibodies act in multiple ways to cause inactivation of pathogens and toxins. Page 2: Goals To describe the structure and function of an antibody. To compare the functions of different antibody classes. To describe the ways in which antibodies cause the destruction or inactivation of pathogens or their toxins. To describe events in B cell activation, including the role of helper T cells and events in the germinal center. To compare active and passive humoral immunity. Page 3: Antibodies: Introduction The terms antibody, immunoglobulin, and gamma globulin are synonymous. The basic antibody molecule is roughly Y-shaped. It consists of four polypeptide chains: two identical heavy chains and two identical light chains bound together by disulfide bonds. The light chains and the heavy chains of antibodies have constant and variable regions. Page 4: Antibodies: Antigen-Binding Site and Stem The variable regions of the heavy and light chains make up the antigen-binding site, which is at the end of the arms of the Y-shaped antibody. The stem of the Y-shaped antibody determines the class of antibody molecule and, therefore, how it interacts with the rest of the immune system. There are 5 classes of immunoglobulins: IgM, IgD, IgG, IgA, and IgE. Page 5: Antibodies: IgG Some antibody classes are specialized for certain functions. IgG is the most abundant antibody in plasma and is formed later in the primary immune response and in the secondary immune response. Together with IgM, it constitutes most of our humoral immunity. Page 6: Antibodies: IgM IgM is secreted early in the primary immune response. Secreted IgM is a pentamer. IgM acts as a B cell antigen receptor on naive B cells. 1 Page 7: Antibodies: IgA IgA is present in secretions such as mucus in the digestive, respiratory, and genitourinary tracts and in milk, sweat, saliva, and tears. Page 8: Antibodies: IgE IgE mediates defenses against parasitic worms and is responsible for the symptoms of allergy. IgE binds to receptors on mast cells and basophils and leads to the release of inflammatory mediators from these cells following interaction with antigen. Page 9: Antibodies: IgD IgD, along with IgM, acts as an antigen receptor on the membranes of naive B cells. The role of IgD is not entirely clear. Page 10: Antibodies: Summary of Actions Antibodies deal with pathogens or toxins primarily by acting as opsonins, marking them for phagocytosis. As a result of antibody binding, neutralization, agglutination, precipitation, or complement activation also occurs. Neutralization occurs when antibody binding prevents the antigen from interacting with the host. Examples are viruses and toxins. Antibody can bind antigens together, forming clumps and, thereby, enhancing phagocytosis. Clumping cells together is called agglutination. When soluble antigens form clumps, they often precipitate. Complement activation by antibody can enhance both opsonization and inflammation and can lead directly to cell lysis. Page 11: B Cell Activation: Antigen Encounter A B cell becomes activated when it encounters the one specific antigen that binds its lymphocyte antigen receptor. This is clonal selection. In lymph nodes, B cells encounter antigen in the outer cortex. Soluble antigen bound to B cell antigen receptors is endocytized, processed, and displayed on MHC proteins. Page 12: B Cell Activation: Role of Helper T Cells In most cases, B cells require help from certain T cells, called helper T cells, to become activated. Activated helper T cells bind to antigen-displaying helper T cells. Activation of B cells involves co-stimulatory signals and cytokines supplied by helper T cells. Page 13: Germinal Center Events Activated B cells undergo clonal expansion with the formation of effector cells and memory cells. The primary immune response begins with clonal expansion. 2 During clonal expansion in germinal centers, affinity maturation and antibody class switching occurs. Plasma cells are antibody-secreting factories. Memory cells circulate throughout the body. Page 14: Active and Passive Humoral Immunity Active humoral immunity is acquired as a result of infection or vaccination and provides memory. Passive humoral immunity is acquired by transferring antibodies from one person to another. It is short-lived and does not provide memory. Page 15: Summary Antibodies are Y-shaped molecules with arms that bind the antigen and with a stem that determines the class of antibody. The five different classes of antibodies (IgG, IgM, IgA, IgE, and IgD) each have different functions. Antibodies mark their targets for destruction either by phagocytosis, complement activation (leading in some cases to cell lysis), agglutination, or neutralization. Helper T cells are crucial for activation of B cells in response to most antigens. Affinity maturation, antibody class switching, and differentiation into plasma cells and memory cells occur in the germinal centers after B cell activation. Humoral immunity can be acquired actively or passively. Study Questions 1. (Goal 1, Page 3) List two synonyms for the word antibody. 2. (Goal 1, Page 3) Describe characteristics of a basic antibody molecule. 3. (Goal 1, Page 4) Where are the antigen-binding sites located on the antibody molecule? 4. (Goal 1, Page 4) What feature of an antibody molecule determines what class it belongs to? 5. (Goal 1, Page 4) Name the five classes of immunoglobulin molecules. 6. (Goal 2, Page 5) Which antibody is most abundant in plasma, and when does it appear? 7. (Goal 2, Page 5) Which two antibody classes are responsible for most humoral responses? 8. (Goal 2, Page 6) Describe the shape of an IgM molecule and relate when it appears. 9. (Goal 2, Page 6) What is the function of an IgM molecule found on the surface of a naive B cell? 10. (Goal 2, Page 7) Where are IgA molecules found? What function do they perform? 11. (Goal 2, Page 8) List the two functions of IgE. 12. (Goal 2, Page 8) Describe what happens when IgE binds to receptors located on basophils and mast cells. 13. (Goal 2, Page 9) Where are IgD molecules found? What can be said about their role in an immune response? 14. (Goal 2, Pages 5–9) Check your understanding of the five classes of antibodies by completing the following table. 3 Immunoglobulin Draw Antibody Location Secretions such as saliva, tears, mucous, and breast milk Function(s) IgM Unclear IgG Secretions such as saliva, tears, mucous, and breast milk 15. (Goal 3, Page 10) Relate the primary method used by antibodies to deal with pathogens and toxins. 16. (Goal 3, Page 10) Identify and explain the four other methods antibodies use to eliminate antigens. Label the five ways antibodies mark antigens for destruction or inactivation by labeling the targets below. 17. (Goal 4, Page 11) Explain where and how B lymphocytes become activated. 18. (Goal 4, Page 11) Describe what happens when soluble antigens bind to a B cell’s antigen receptors. 19. (Goal 4, Page 12) What is the role of the helper T lymphocyte in B cell activation? 20. (Goal 4, Page 13) Describe what happens in a lymph node’s germinal center during a primary response. 21. (Goal 4, Page 13) What is the name of the activated B cell once if has become an “antibody producing factory”? 22. (Goal 4, Page 13) What happens to the memory cells produced during clonal expansion? 23. (Goal 5, Page 14) When does a person acquire active humoral immunity? 4 24. (Goal 5, Page 14) When does a person acquire passive humoral immunity? 25. (Goal 5, Page 14) Explain the differences between active and passive humoral immunity. 26. Complete the following hmoral immunity flowchart by filling in the six boxes. Summary Fill-in-the-blanks. Fill in each blank with the correct term. Antibodies are ___________-shaped molecules whose arms bind the antigen and whose stem determines the class of antibody. The 5 different classes of antibodies (_____, _____, _____, _____, and _____) have different functions. Antibodies mark their targets for __________________ either by phagocytosis, complement activation (leading to cell lysis), agglutination, or neutralization. ________________ are crucial for activation of B cells in response to most antigens. 5 Affinity maturation, antibody class switching and differentiation into ___________ cells occur in the _______________ _______________ of a lymph node after B cell activation. Humoral immunity can be acquired ____________________ or ___________________. 6