Chapter 5 Learning Objectives Define the following terms:Antibody Immunoglobulin CDR Serum Titer Isotype Fab Fc Chaperone J chain Half-life Hinge region Hybridomas Monoclonal antibodies Myeloma CD20 FcRn Antigenic determinant Epitope Affinity Avidity Valency Kd Immune complex Disulfide bonds BiP Calnexin Pepsin Papain Mucosal immunity Neonatal immunity HAT media Antibody recycling Immunogen Proteolysis Neoantigen Denaturation Learning Objectives - Important concepts to know At the end of this chapter, you should be able to: 1. Explain the various differences in the antigen receptors for B cell, T cells, and APCs, including: a. the type of antigen they bind b. the number of antigens they can bind c. the types of antigenic determinants they can recognize d. the structure of their antigen-binding sites 2. List the various locations in which antibodies can be found in the body. In a given blood sample, where are the antibodies located? 3. Identify the location within the cell where antibodies are made? What is the purpose of the chaperone proteins? 4. Describe the structure of an antibody. 5. Discuss the correlation between antibody isotype and heavy chain genes. 6. Identify the specific location on an antibody where antigen binds. 7. Discuss what pepsin and papain are and their purpose in Figure 5-3.8. Compare the five antibody isotypes, including: a. their relative concentration in serum b. their relative concentration in the body c. their relative half-life d. which isotypes can be secreted and which are membrane bound e. their form(s) when secreted (monomer, dimer, etc.) f. their effector functions g. their location in the body 9. Discuss the purpose of the hinge region of an antibody. 10. Explain the process of how monoclonal antibodies are made in Figure 5-9, including: a. the discovery and purpose of monoclonal antibodies b. the model that is used to make them including the cells that are involved c. how monoclonal antibodies are selected for d. the various uses of monoclonal antibodies (hint: our text lists 5 uses) 11. Identify the antibody isotype with the longest half-life and rationalize why this is so. Hypothesize why this is important to therapeutics. 12. Compare the 3 different types of antigenic determinants that are used to stimulate an immune response, including: a. the three antigenic determinants and their structure b. the potential consequences of denaturation for each antigenic determinant 13. Explain the difference between affinity and avidity, including: a. which antibody isotype has the highest avidity (and why?) b. the correlation between affinity and Kd c. the correlation between affinity and avidity d. the correlation between avidity and valency14. Discuss the importance of immune complexes to the immune response, including: a. the purpose they serve b. how, why, and when are they formed c. the difference between the zone of equivalence, zone of antigen excess, and zone of antibody excess, relating particularly to the immune response d. the potential consequences of small and large immune complexes (which immune complex, small or large, is better and why?) 15. Review the numerous changes an antibody can undergo to increase the efficacy of the immune response. What is the significance of each of these changes in relation to its ability to recognize antigen? In its ability to perform their effector functions? Please look up the following information in your textbook: 1. What is serology? (p. 87) 2. Please read the section on “Synthesis, Assembly, and Expression of IgG Molecules” on page 97 and 98 and be able to describe the process of antibody production beginning with B cell development until antibody secretion. Please also see Figure 5-10 on page 99. 3. From Table 5-3 on page 98, please identify the disease(s) that each of the following targets of monoclonal antibodies are useful for: - BAFF - CD20 - CD52 - IgE - HER2/Neu For example, a monoclonal antibody that is used to treat B cell lymphoma is called an anti-CD20 antibody (this terminology always uses the term “anti-” to signify it is an antibody, and the target antigen in this instance is CD20). 4. Please read the section called “Features Related to Antigen Recognition” on pages 102 and 103 in your textbook and discuss how specificity, diversity and affinity maturation affect antigen