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Immunoglobulins and the Immune System

Learning Objectives and Guiding Questions

submitted by Charles Faust, Ph.D.

Reading assignment: Meisenberg, pp 524-534, and the class handout.

1. Many components of infectious agents are antigens. Describe an antigen or immunogen.

1.1 What are the typical infectious agents that are usually immunogenic?

1.2 What properties of a molecule are usually expected for it to be immunogenic?

1.3 What types of molecules typically elicit an immune response?

1.4 What is an epitope, antigenic determinant and hapten?

1.5 What is the typical size of an epitope or antigenic determinant?

1.6 How many antigenic determinants or epitopes can an antigen have?

2. Describe an antibody or immunoglobulin molecule.

2.1 What is the polypeptide structure of the basic monomeric immunoglobulin unit?

2.2 What is the basic structural unit of the immunoglobulin light and heavy chain?

2.3 How many domains does a light chain have? How many for a heavy chain?

2.4 Which portion of the light and heavy chains contains the variable region domains and what is their purpose? What is a paratope?

2.5 Which portion of the light and heavy chains contains the constant region domains and what is their purpose?

2.6 Why are these domain units called variable region and constant region and what is their typical length or size?

2.7 How many basic types of light chains are there? How many basic types of heavy chains are there?

2.8 What are Fab and Fc fragments of immunoglobulins?

2.9 Why is an antibody known as a glycoprotein?

2.10 What distinguishes interchain from intrachain disulfide bonds?

2.11 What are the antibody types with four-domain heavy chains and with five-domain heavy chains? What other important structural feature distinguishes the two groups?

2.12 What is one important function of the immunoglobulin hinge region?

2.13 Which antibody classes fix complement? Cross the placenta? Bind mast cells?

2.14 What distinguishes monomeric immunoglobulins from polymeric immunoglobulins? Which classes can exist in polymeric form and why? Which two non-immunoglobulin polypeptide chains does secretory IgA contain?

2.15 Characterize J-chain and secretory piece, and which cells make each polypeptide?

2.16 What is the main difference between a secreted antibody and an antibody that is an integral membrane protein, if both recognize exactly the same epitope? Which group of antibodies is able to exist in only a monomeric form?

2.17 What important accessory polypeptides are associated with the integral membrane form of the antibody and what is their function?

2.18 What is basic structure of the so-called immunoglobulin fold or motif?

2.19 What are hypervariable regions and what is their purpose? Where are they found and how many does each antibody light and heavy chain have? How many total per paratope?

2.20 What determines the valency of an immunoglobulin molecule? What is the range of valency for the different classes of antibodies?

3. Describe the fundamental cell biology of the immune system.

3.1 What are the three basic cell types involved in the immune response?

3.2 What are the two principal arms of the immune system and what cell types are important to each?

3.3 What are the functions of a memory B-cell and a plasma cell? What are some of the properties of each type?

3.4 When antigen is recognized by the antibody, as integral membrane, B-cell protein, i.e., the antigen receptor, this occurs via a complementary epitope-paratope interaction, and the B-cell becomes activated. What three major events are likely to take place as a consequence of this B-cell activation?

3.5 What are the four phases of the primary immune response?

3.6 B-cells are activated what basic mechanism?

3.7 What is the meaning of clonal expansion, following B-cell activation?

3.8 Can you contrast a primary antibody response with a secondary antibody response. Which immunoglobulin class always appears first? Following booster immunizations which immunoglobulin class predominates in the plasma? Which in the mucous secretions?

3.9 What are the two principal cell types involved in an atopic response?

3.10 Antibody mediated, cell killing can be complement dependent or complement independent. What are the basic features of the complement independent mechanism by which antibody can cause cell cytotoxicity and lysis? Why does complement lyse cells?

3.11 Macrophages, like B-cells and T-cells, can become activated. How can activated macrophages kill target cells?

3.12 When an antigen fragment is presented by a major histocompatibility complex protein, type I or type II, and is also recognized by the T-cell antigen receptor, this occurs via a complementary epitope-paratope interaction, and the T-cell becomes activated. What three major events are likely to take place as a consequence of this T-cell activation?

3.13 What are the three types of T-cells? Which T-cell types are considered regulatory and why? What is the function of a killer T-cell?

4. Describe tests to characterize antibodies and to use the antibodies in clinical tests.

4.1 What is a plasma protein profile and how can this sometimes distinguish between a normal condition versus a pathological condition?

4.2 What is a monoclonal antibody, why is it made and how is it generally produced?

4.3 How many unique paratopes does a monoclonal antibody have? How many unique light chains? How many unique heavy chains?

4.4 In what sort of clinical tests can monoclonal antibodies be useful?

4.5 How might monoclonal antibodies be developed for immunotherapy?

4.6 What is colostrum and how might one detect and quantify IgA antibodies in it?

4.7 What is a typical format for an immunoassay, e.g., the sandwich immunoassay?

4.8 What is a western blot?

5. Describe antigen-antibody reactions as a normal consequence of the immune response.

5.1 What is the significance or importance of antigen-antibody reactions?

5.2 Can you name six different types of antigen-antibody reactions that one is likely to experience during the course of various immune responses?

5.3 What distinguishes agglutination from opsonization? How does this compare with precipitation?

5.4 What mechanism is most effective for enzyme inactivation? Toxin inactivation? Virus neutralization?

5.5 What is complement fixation? What is its purpose and principal outcome?

5.6 What is the outcome of atopic antigen-antibody reactions? What antibody class is responsible for these? What is an allergen?

5.7 Why does IgE bind to mast cells and tissue basophils?

5.8 What happens to a mast cell or tissue basophil after its bound IgE recognizes and binds an antigen (allergen), producing an IgE-allergen complex on the mast cell surface?

6. Describe immune system dysfunctions.

6.1 What are the three basic types of immune system dysfunctions?

6.2 What kind of immune deficiency diseases are there?

6.3 What are abnormal lymphocyte proliferation diseases?

6.4 What are autoimmune diseases?

6.5 Why can HIV lead to the immune dysfunction known as AIDS?

6.6 What is the basic mechanism by which AIDS occurs?

7. Describe the T-cell receptor and its function.

7.1 What two simultaneous recognition events are required for T-cell effector function?

7.2 What is the basic structure of the T-cell antigen receptor and why is it a transmembrane protein?

7.3 What are the T-cell antigen receptor's three important accessory polypeptides and what is their principal function?

7.4 A mature T-cell also has one of two types of co-receptors closely associated with the specific antigen recognition receptor. What is each co-receptor called and what are their purposes in the scheme of antigen fragment presentation and subsequent recognition?

7.5 How does the T-cell antigen receptor complex compare with the B-cell antigen receptor complex, including the associated signal transducing complex proteins?

7.6 What is the principal distinction between antigen recognition by an antigen specific B-cell receptor versus an antigen specific T-cell receptor, regarding the antigen?

7.7 What are the T-cell antigen receptor variable region domains, where are they in the polypeptide, how many make a paratope and where are their hypervariable regions?

7.8 Where are the T-cell constant region domains, and where are they in the T-cell polypeptide?

7.9 Do these T-cell variable and constant region domains have an immunoglobulin-like structural fold and why?

7.10 What is the significance of intra-chain and interchain disulfides bonds in the T-cell antigen receptor?

7.11 Which integral membrane proteins are associated with most cellular immune responses?

8. Describe the major histocompatibility complex (MHC) proteins (transplantation antigens) and their function.

8.1 What are class I and II MHC proteins, and what is their structure and function?

8.2 What fundamental structural motif of the class I and class II MHC proteins bind the antigen fragment for presentation to the T-cell antigen recognition receptor?

8.3 Which MHC class proteins do the co-receptors CD4 (T4) and CD8 (T8) recognize and what T-cell effector function occurs after its recognition and recognition of antigen fragment?

8.4 Which protein structure is one of the most important receptors for the recognition, binding and internalization of the human immunodeficiency virus (HIV) responsible for AIDS (acquired immunodeficiency syndrome)? Which prominent immune cell type bears this structure? Which viral structural protein binds to this T-cell structure?

8.5 Which cells bear MHC class I proteins, and which cells bear MHC class II proteins?

8.6 What is the major protein involved in cytotoxic activity of killer T-cells and how does this work? Can you contrast it with cytolysin and complement?

8.7 What distinguishes whether a cell presents an antigen fragment via a class I or class II MHC protein complex? What is important about the intracellular, trafficking pathways used by each? Which cell types display both classes of MHC protein complexes?

9. Describe cytokine production and the role of these peptide hormones in the immune response.

9.1 What are cytokines, lymphokines and monokines?

9.2 When during the course of an immune response might one expect to find cytokines produced and why?

9.3 What are two principal functions of cytokines, following immune cell activation?

10. Describe the fundamental molecular biology of the immune system.

10.1 The human genome (specific chromosomes) contains the genes encoding all the various light and heavy chain variable and constant region domains. What process leads to formation of a functional variable region domain for both the B-cell or T-cell antigen-specific, recognition receptor?

10.2 What is allelic exclusion and why is it important?

10.3 What is immunoglobulin heavy chain class switching, and how is this explained at the level of the gene (DNA)? Does this affect the light chain?

10.4 There are two DNA recombination events that can occur in B-cells, formation of a functional gene encoding a variable region domain and heavy chain class switching. Are these the same mechanism and why? Which one always occurs first? What is the purpose of heavy chain class switching? Which antibody class is always made first and why and what happens to epitope recognition after the switching?

Copyright © 1998 Charles Faust, Ph.D., Department of Cell Biology & Biochemistry, TTUHSC

Last revised 10/04/99