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Home , Antibody, Degranulation, Isotype (immunology)

John A. Burns School of Medicine JABSOM e-Learning for Basic e-Learning

To navigate: 1 1. Yellow navigation bar 2 : Basics 2. Back and Fwd buttons Estimated Learning Time: 30 min. 3 4 Back Fwd 5 One :: General Structure 6 7 Identify the Parts of an Antibody 8 Two :: Isotypes 9 Identify Antibody Isotypes 10 [ Start Now! ] 11 Three :: Function 12 Match Antibody Functions With Isotypes 13 14 Four :: Diversity 15 Explain Antibody Diversity 16 17 Antibody 18 Advice 19 20 21 Allow Hi! 22 me to be your Ctrl + L 23 Command + L guide... find me 24 FULL SCREEN at the bottom 25 in Adobe Acrobat of each page! 26

Contributors William L. Gosnell, Ph.D. Software Requirements: Kenton J. Kramer, Ph.D. Karen M. Yamaga, Ph.D. Click to download the latest versions Department of Tropical Medicine, and JABSOM John A. Burns School of Medicine e-Learning e-Learning for Basic Sciences OVERVIEW 1 2 3 Contents 4 5 instructional By the end of this module you should be This One :: General Structure 6 module was designed with you able to: Identify the Parts of an Antibody Page 3 7 in mind. Understanding antibody 1. Identify the parts of an antibody. basics will help you understand 2. Identify antibody isotypes. Two :: Isotypes 8 immunology concepts that are 3. Match antibody functions with isotypes. Identify Antibody Isotypes Page 9 9 necessary to pass USMLE board 4. Explain antibody diversity from 10 exams - the first step on your way somatic recombination. to becoming a doctor. Three :: Function 11 Please start with Section One... Match Antibody Functions With Isotypes Page 13 12 Four :: Diversity Page 19 13 Explain Antibody Diversity 14 15 16 17 18 19 20 Acknowledgements 21 John A. Burns School of Medicine College of Education Ctrl + L 22 Department of Tropical Medicine, Department of Educational Command + L 23 Medical Microbiology & Pharmacology Office of Medical Education Technology Sandra P. Chang, Ph.D. Richard T. Kasuya, M.D., M.S.Ed. Catherine P. Fulford, Ph.D. FULL SCREEN 24 William L. Gosnell, Ph.D. Joshua L. Jacobs, M.D. Ariana Eichelberger, M.Ed. in Adobe Acrobat Kenton J. Kramer, Ph.D. Gwen S. Naguwa, M.D. 25 Leslie Q. Tam, Ph.D. Marlene Lindberg, Ph.D. 26 Karen M. Yamaga, Ph.D.

Hi folks! Before you start... use the FULL SCREEN view to maximize the experience. Click the Fwd button to advance... Back Fwd JABSOM John A. Burns School of Medicine e-Learning e-Learning for Basic Sciences

1 2 3 4 5 6 7 8 CHAPTER ONE 9 10 11 GENERAL STRUCTURE 12 13 14 15 16 17 Objective: Identify the Parts of an Antibody 18 19 20 21 22 23 24 25 26

Back Fwd JABSOM John A. Burns School of Medicine e-Learning e-Learning for Basic Sciences ONE GENERAL STRUCTURE 1 2 3 4 Overview 5 Also known as immunoglobulins (abbreviated as Ig), 6 are molecules found in 7 and bodily fluids of humans and other 8 . They are used by the to identify and destroy foreign 9 substances to the body, such as 10 and . 11 More specifically, antibodies are Y- 12 shaped consisting of four 13 polypeptide chains linked covalently by bonds (Figure 1). They act as 14 -specific receptors on B-cells, 15 and when secreted by plasma cells, 16 mediate humoral responses. 17 18 19 Figure 1. Basic antibody structure (monomer IgG). 20 Y-shaped molecule formed by four polypeptide 21 chains, indicated by two red and two blue bars. Small dark lines indicate disulfide bonds. 22 23 24 Definition: Antibody - also called immunoglobulin (Ig), a Y-shaped 25 molecule found in human blood or bodily fluids; used by 26 the immune system to find and destroy .

We antibodies know how to stay in shape... “Y” shape, that is! See the next page to learn what makes our shape. Back Fwd JABSOM John A. Burns School of Medicine e-Learning e-Learning for Basic Sciences ONE GENERAL STRUCTURE 1 2 1. Heavy & Light Chains 3 4 3. Framework & Hypervariable Antibodies contain two identical 5 heavy chains and two identical Regions 6 light chains. Bonded together 7 by the disulfide bonds, they form The variable region is made up of the Y-shaped molecule (Figure 2). two parts: the and 8 hypervariable region. The framework 9 region is structurally similar. But most 10 2. Variable & Constant Regions importantly, the hypervariable regions are extremely diverse, as the name 11 indicates. This allows for the creation of 12 The heavy and light chains are a wide variety of antibodies, and in turn, subdivided into two regions or 13 allows the immune system to recognize domains: the variable region and protect against a wide variety of 14 and constant region. Constant antigens. 15 regions have the same sequences, while variable regions Antigen specificity is determined by the 16 have different amino acid sequences. amino acids in the hypervariable regions. 17 Variable regions are responsible for 18 antigen recognition and binding. 19 20 Figure 2. Basic antibody structure (monomer IgG). Red and blue areas indicate light 21 and heavy chains respectively. Light and dark areas of each chain indicate the variable and constant regions respectively. Small dark lines indicate disulfide bonds. 22 23 24 Synonyms: Region = Domain 25 Hypervariable Region = Complementarity Determining Region (CDR) 26

Just like human beings, our “anatomy” is very similar Back Fwd and yet we are so diverse - keep this in mind as we progress... JABSOM John A. Burns School of Medicine e-Learning e-Learning for Basic Sciences ONE GENERAL STRUCTURE 1 2 3 4 QUICK REVIEW Think 5 6 Fast! 7 Answer these quick questions 8 before you move on... 9 10 11 4. Referring to the antibody diagram, the hypervariable region is found in 12 1. An antibody: letter: 13 a. avoids antigen contact. 2. Referring to the antibody diagram, a. (a) 14 b. has one disulfide bond. the light and heavy chains are indicated by letters: b. (b) 15 3. Referring to the antibody diagram, c. has only two polypeptide chains. 16 a. (a) and (b) respectively the variable and constant regions c. (c) d. is a glycoprotein. b. (a) and (c) respectively are indicated by letters: d. (d) 17 18 c. (b) and (d) respectively a. (a) and (b) respectively 19 d. (c) and (d) respectively b. (a) and (c) respectively c. (b) and (d) respectively 20 d. (c) and (d) respectively 21 22 23 24 25 26

Did you get them all correct? Good! Let’s move on to the last section on General Structure... Back Fwd JABSOM John A. Burns School of Medicine e-Learning e-Learning for Basic Sciences ONE GENERAL STRUCTURE 1 2 4. Proteolytically Derived 3 Fragments of IgG 4 5 Antibodies can be broken down -DIGESTED FRAGMENTS -DIGESTED FRAGMENTS 6 (proteolysis) into different fragments by two common . 7 8 Pepsin is a digestive protease created by stomach cells that degrade food 9 . Papain is a cysteine protease, 10 commonly found in papaya, also can 11 digest proteins. As a result of using either, the -based antibodies can 12 be broken into fragments. 13 The tips of the Fab region, composed of 14 heavy and light chains, are responsible 15 for recognizing and binding to foreign objects. At the base of the antibody 16 is the Fc region, composed of two 17 heavy chains, and by binding to specific 18 proteins ensures that the appropriate 19 is generated. Figure 3. Proteolytically derived fragments of an antibody (monomer IgG) from pepsin and papain. On the 20 Figure 2 illustrates the fragments created left, the action of pepsin results in one large F(ab’)2 fragment and many different low molecular weight when pepsin and papain digest antibody fragments. On the right, the action of papain results in two Fab fragments and one Fc fragment. 21 IgG. 22 23 24 Definitions: Proteolysis - the breakdown of proteins into and amino acids; IgG - an immunoglobulin (Ig) with a gamma (G) heavy chain; 25 Proteolytically (adj.) the most common antibody isotype 26

Like a surgeon’s scalpel, pepsin and papain cuts us apart. It’s not exactly a “Nip/Tuck” cosmetic procedure... Back Fwd JABSOM John A. Burns School of Medicine e-Learning e-Learning for Basic Sciences ONE GENERAL STRUCTURE 1 2 3 4 QUICK REVIEW Think 5 6 Fast! 7 Answer these quick questions 8 before you move on... 9 10 4. Referring to the antibody diagrams, 11 the fragments caused by the actions 2. Pepsin and papain are of pepsin and papain are: 12 a. antibody fragments. a. (a) and (b); (c) and (d) 13 b. digestive enzymes. respectively. 14 c. fragments that form antibodies. b. (a) and (d); (c) and (b) 15 3. Referring to the antibody diagrams, respectively. 1. Proteolysis of an antibody is when 16 d. molecules that split disulfide the F(ab’) , Fab, and Fc fragment a. an fragments an 2 c. (b) and (c); (a) and (d) bonds. are: 17 antibody. respectively. a. (a), (b) and (c) respectively 18 b. its disulfide bonds split. d. (c) and (d); (a) and (b) b. (a), (b) and (d) respectively respectively. 19 c. its light chains are separated 20 from the heavy chains c. (a), (c) and (d) respectively 21 d. protein fragments form an d. (b), (c) and (d) respectively antibody. 22 23 24 25 26

Now that you know how we antibodies are structured, Let’s move on... Back Fwd JABSOM John A. Burns School of Medicine e-Learning e-Learning for Basic Sciences

1 2 3 4 5 6 7 8 CHAPTER TWO 9 10 11 ISOTYPES 12 13 14 15 16 17 Objective: Identify Antibody Isotypes 18 19 20 21 22 23 24 25 26

Back Fwd JABSOM John A. Burns School of Medicine e-Learning e-Learning for Basic Sciences TWO ISOTYPES 1 2 3 4 Overview regions 5 Constant of heavy and light chains have the same amino acid 6 sequences thus defining antibody isotypes, or 7 classes of antibodies. 8 In light chains, there are two isotypes, or classes: (κ) and lambda (λ). 9 In heavy chains, there are five 10 major isotypes, or classes: alpha Table 1. Heavy and light chain isotypes. 11 (α), gamma (γ), delta (δ), epsilon 12 (ε), and mu (μ). Antibodies are Light Chain Heavy Chain 13 generally classified by heavy 1. kappa (κ) 1. alpha (α)* chain isotypes. 14 2. lambda (λ) 2. gamma (γ)* * Alpha has two subclasses and 15 gamma has four subclasses, 3. delta (δ) 16 which make a total of nine heavy 4. epsilon (ε) chain isotypes. But only the five 17 major isotypes will be covered. 5. mu (μ) 18 Table 1 lists heavy and light chain 19 isotypes of the constant region. 20 21 22 23 24 Definitions: Isotype - the class of an antibody light or heavy chain. 25 26

Understanding isotypes is your first step to understanding our diversity... Think of our isotypes like human ethnicities. Back Fwd JABSOM John A. Burns School of Medicine e-Learning e-Learning for Basic Sciences TWO ISOTYPES 1 2 1. Heavy Chain Isotypes Table 2. Illustrations of heavy chain isotypes, including presence of a J-chain and secretory piece, where applicable. 3 4 There are three general immunoglobulin 5 structures, defined by heavy chain isotypes - the monomer, dimer, and the 6 pentamer. 7 The monomer isotypes are IgG (gamma), 8 IgD (delta), and IgE (epsilon). The dimer 9 isotype is IgA (alpha) and the pentamer 10 isotype is IgM (mu). 11 Heavy chain isotopes are illustrated in Table 2. 12 The J-chain (“J” stands for joining) 13 connects monomers to form dimers and Form Monomer Dimer Pentamer 14 pentamers. J-chains are produced by B Heavy Chain Ig IgG IgD IgE IgA IgM 15 cells and plasma cells. Heavy Chain Isotype gamma delta epsilon alpha mu 16 A secretory piece might be attached to a dimer if it passes through epithelial cells. J-chain ( ) --- Yes Yes 17 These are commonly found in saliva and Secretory piece ( ) --- Yes - 18 . 19 20 21 22 23 24 Definitions: J-chain - or “Joining chain” is a protein produced by B-cells and plasma cells that connects a monomer to form a dimer or pentamer. 25 Secretory piece - a polypeptide that attaches to a dimer (IgA) when it passes through epithelial cells in mucosal areas. 26

Dimers and pentamers show you that we can work in groups! Back Fwd In the next chapter you’ll learn how each isotype functions... JABSOM John A. Burns School of Medicine e-Learning e-Learning for Basic Sciences TWO ISOTYPES 1 2 2. Which one of the following is NOT 3. Which one of the following is NOT true about a J-chain? true about a secretory piece? 3 a. Connects monomers to form a. Attaches ot a dimer. 4 dimers and pentamers. b. Attaches to an antibody when it 5 b. Connects IgA to form IgG and passes through epithelial cells. 6 QUICK REVIEW Think IgM. c. Found in saliva and tears. 7 c. Is created from B-cells and d. Found in the heart. 8 plasma cells. 9 Fast! d. Is labeled “J” for Joining. Answer these quick questions 10 before you move on... 11 12 4. Using the table below, write IgA, IgD, IgE, IgG, and IgM under the corresponding antibody structure. 13 14 1. Using the table to the right, correctly Light Chain Heavy Chain type the constant region isotype 15 names: alpha, delta, epsilon, 1. 1. 16 gamma, kappa, lambda, and mu. 2. 2. 17 3. 18 4. 19 5. 20 Monomer Dimer Pentamer 21 22 23 24 25 26

Yes! another REVIEW! Practice what you learn - you’ll need it in the next chapter... Back Fwd JABSOM John A. Burns School of Medicine e-Learning e-Learning for Basic Sciences

1 2 3 4 5 6 7 8 CHAPTER THREE 9 10 11 FUNCTION 12 13 14 15 16 17 Objective: Match Antibody Functions With Isotypes 18 19 20 21 22 23 24 25 26

Back Fwd JABSOM John A. Burns School of Medicine e-Learning e-Learning for Basic Sciences THREE FUNCTION 1 2 3 4 Overview Anti- Table 3. Overview of antibody functions. 5 6 7 bodies 8 are produced by B-cells in the bone marrow, exist freely in the bloodstream, 9 and each is constructed to respond 10 specifically to one antigen. Antibodies 11 function in three main ways: Function IgG IgD IgE IgA IgM 12 1. bind to antigens to prevent them 1. Antigen binding Yes Yes Yes Yes Yes 13 from entering or damaging cells; 2. Antibody-dependent Yes - - - - 14 2. stimulate removal of antigens; and (ADCC) 15 3. trigger antigen destruction 3. Opsonization Yes - - - - by stimulating other immune 16 4. Placental transport Yes - - - - responses. 17 Antibody functions are specific to heavy 5. Classical complement pathway Yes - - - Yes 18 chain isotypes. Table 3 provides an 6. Mature B-cell receptor - Yes - - Yes 19 overview of antibody functions. The 7. Memory B-cell receptor Yes - Yes Yes - following pages will describe each 20 function more specifically. 8. Triggers - - Yes - - 21 22 23 24 25 26

It’s easier said than done, but antibodies protect your body - in more ways than one... Our functions are based on isotypes. Back Fwd JABSOM John A. Burns School of Medicine e-Learning e-Learning for Basic Sciences THREE FUNCTION 1 2 2. Antibody-Dependent Cell 3 1. Antigen Binding Cytotoxicity (ADCC) 3. Opsonization 4. Placental Transport 4 5 The most basic function of an antibody Only IgG has the function of ADCC, which Another function solely of IgG where it Only one isotype, IgG, is capable of 6 is to bind to an antigen. All antibody is the cell-killing ability (cytotoxicity) of coats particles for , or the transporting across the from isotypes, IgA, IgD, IgE, IgG and IgM have certain . Lymphocytes will engulfment by a . to . The purpose of this is 7 this capacity. attack and destroy a target cell that has are white blood cells that engulf and to transfer maternal to the 8 been bound by IgG. digest antigens. fetus. 9 10 11 12 13 14 Play 15 01:18 16 17 18 Figure 4. Antibodies (yellow) bind to an Figure 5. Lymphocytes (brown) attacking Figure 6. Animation of opsonization. Figure 7. Antibodies transporting from 19 antigen. a target cell (green). (Click to play) placenta to fetus. 20 - IgA, IgD, IgE, IgG, IgM - - IgG - - IgG - - IgG - 21 22 23 24 Definitions: Cytotoxicity - the quality of being toxic to a cell. Illustrations: Adobe Stock Photos (Figures 5 & 7) 25 Phagocyte - white blood cells that engulf and digest antigens. Nucleus Medical Art. (Figures 4 & 6) 26

The first four functions are listed here. Pay attention to the isotypes under each function... Back Fwd JABSOM John A. Burns School of Medicine e-Learning e-Learning for Basic Sciences THREE FUNCTION 1 2 3 5. Classical Complement Pathway 6. Mature B-cell receptor 7. Memory B-cell receptor 8. Mast cell degranulation 4 5 When antibodies IgG and IgM bind to When antibodies IgD or an IgM When antibodies IgA, IgE, and IgG serve When an binds to two or 6 an antigen and initiates a biochemical monomer (one four-chain unit) serve as antigen receptors on a memory B-cell more IgE antibodies on a mast cell cascade consisting of a number of blood as antigen receptors on a mature B-cell surface. and activates degranulation, which is 7 proteins and leads to the killing of surface. B-cells originate in the bone the release granules and hormonal 8 . marrow (the “B” is for bone marrow). mediators that create allergic reactions. 9 10 11 12 13 14 Play 15 00:25 16 17 18 Figure 8. Illustration of classical Figure 9. Illustration of a mature B-cell Figure 10. Illustration of a memory B-cell Figure 11. Animation of mast cell 19 complement pathway. with an IgD antibody on its surface. with an IgG antibody on its surface. degranulation. (Click to play) 20 - IgG, IgM - - IgD, IgM - - IgA, IgE, IgG - - IgE - 21 22 23 24 Definitions: Allergen - a non-parasitic antigen that creates allergic reactions. Illustrations: Craig Okumura (Figures 7 - 10) 25 B-cells - white blood cells that make antibodies and are part of the humoral immune response. Animation: Unknown. 26 - a disease-causing .

The last four functions are listed here. Pay attention to the isotypes under each function... Back Fwd JABSOM John A. Burns School of Medicine e-Learning e-Learning for Basic Sciences THREE FUNCTION 1 2 Table 4. Antibody functions and characteristics (denoted by •) by isotype. 3 4 5 6 7 8 IgG IgD IgE IgA IgM 9 10 1. Binds to antigens. 1. Binds to antigens. 1. Binds to antigens. 1. Binds to antigens. 1. Binds to antigens. 11 2. Transports across the placenta 2. Present in mature B-cells at 2. Bridging two IgE on cell 2. Serves as memory B-cell 2. Activates classical complement from mother to fetus. very high levels. triggers mast cell receptor. pathway. 12 degranulation. 13 3. Mediates antibody-dependent 3. Serves as mature B-cell • Protects areas of mucosal 3. Serves as mature B-cell 14 cell cytotoxicity (ADCC). receptor. 3. Serves as memory B-cell (i.e. , saliva, receptor. receptor. 15 4. Activates opsonization. • Has a very low concentration tears, and respiratory, • Present as a pentamer with a 5. Activates classical complement in plasma. • Has a very low concentration intestinal and urogenital J-chain and disulfide bonds. 16 tracts). pathway. in plasma as a monomer. • Is the first antibody to 17 • Present as a dimer with a 6. Serves as memory B-cell • Mediates allergic reactions. appear after an or 18 receptor. J-chain and a secretory piece . • Provides immunity against attaches during passage 19 parasites (i.e. worms). • First antibody an infant makes. • Has the highest concentration through epithelial cells. 20 in plasma. 21 22 23 24 25 26

The characteristics are interesting facts, but... Remember the functions! Back Fwd JABSOM John A. Burns School of Medicine e-Learning e-Learning for Basic Sciences THREE FUNCTION 1 2 3 4 5 6 QUICK REVIEW Think 7 8 Fast! 9 Answer these quick questions 10 before you move on... 11 12 Function IgG IgD IgE IgA IgM 13 1. Antigen binding 1. Match each antibody 14 2. Antibody-dependent cell cytotoxicity function with the correct (ADCC) 15 isotype by clicking on the correct table cells to the 3. Opsonization 16 right. 4. Placental transport 17 A green “X” indicates a 5. Classical complement pathway 18 correct answer and a red 6. Mature B-cell reception 19 “X” is an incorrect answer. 20 (Remember, isotypes have 7. Memory B-cell reception multiple functions.) 8. Triggers mast cell degranulation 21 22 23 24 25 26

This review is quite challenging. Feel free to go back, if necessary, to recall the details. Back Fwd JABSOM John A. Burns School of Medicine e-Learning e-Learning for Basic Sciences

1 2 3 4 5 6 7 8 CHAPTER FOUR 9 10 11 DIVERSITY 12 13 14 15 16 17 Objective: Explain Antibody Diversity 18 19 20 21 22 23 24 25 26

Back Fwd JABSOM John A. Burns School of Medicine e-Learning e-Learning for Basic Sciences FOUR DIVERSITY 1 2 3 4 Overview 5 Everyday, 6 the is subjected to Antibody diversity can be illustrated chain isotypes described in Section 7 numerous foreign substances at the genetic level. Recall from Two. Combine these two factors and and the immune system must Section One that the hypervariable a large number of unique antibodies 8 be prepared to recognize and regions are extremely diverse and can be formed. 9 combat each one. that there are several heavy and light One such mechanism is somatic 10 recombination, which is the unique 11 genetic encoding of a variable region. It is also known as V(D)J 12 recombination - referring to the 13 variable (V), diversity (D), and 14 joining (J) region . 15 16 1. Heavy vs. Light Chain Genes 17 18 The V, D and J segments are found in heavy chains, but only V and J 19 segments are found in light chains. 20 See Figure 12. 21 Figure 12. Difference between heavy and light chain genes (~ indicates total number of genes, such as ~65 is “up to 65”). 22 23 24 Definition: Somatic recombination or V(D)J recombination - the unique genetic encoding of a variable region. Illustration: William L. Gosnell, Ph.D. 25 26

Great job in making it to the last chapter of this module - you will learn about our Genes (no not Jeans), that make us so diverse... Back Fwd JABSOM John A. Burns School of Medicine e-Learning e-Learning for Basic Sciences FOUR DIVERSITY 1 2 2. Formation of heavy and light 3 chain variable regions 4 5 Bone marrow is the site where 6 developing B-cells assemble variable region genes. 7 Single V, D, J, and constant (C) 8 segments randomly combine in that Play 9 order to form the heavy chain. Single 10 V, J, and C gene segments randomly combine in that order to form the light 01:03 11 chain (Figure 13). 12 But once a B-cell forms a functional 13 antibody, it can only produce antibodies 14 with different constant regions. The variable regions are the same. 15 16 Multiple copies of each type of gene Figure 13. Animation of somatic recombination. (Click to play animation) segment are available and different 17 combinations of gene segments can be 18 used to generate each antibody variable 19 region. This process generates a large number of antibodies. 20 21 22 23 24 Animation: William L. Gosnell, Ph.D. 25 26

Now you know about gene types and how they’re ordered, this Back Fwd animation shows you how the light and heavy chains are formed. JABSOM John A. Burns School of Medicine e-Learning e-Learning for Basic Sciences FOUR DIVERSITY 1 2 3. Gene Combinations Table 5. Total number of heavy and light chain gene segments. 3 4 Light Chain Genes Heavy Chain Genes The total number of individual gene Segment 5 segments is relatively small (Table 5). κ λ H However, when combined in the form 6 of an antibody, there are over 3 million Variable (V) 40 30 65 7 possible combinations (Table 6). Diversity (D) 0 0 27 8 When the human body is subjected to Joining (J) 5 4 6 9 numerous foreign substances, antibody 10 diversity from somatic recombination SUB-TOTAL (V + D + J) 45 34 98 11 is one of the reasons why the immune TOTAL NUMBER OF GENES 45 + 34 + 98 = 177 system is prepared to recognize and 12 combat almost every one. 13 Note: There are other processes that Table 6. Total number of gene combinations. 14 increase antibody diversity, such Light Chain Genes Heavy Chain Genes as , affinity Segment 15 maturation, and class switching, but will κ λ H 16 not be covered here. Variable (V) 40 30 65 17 Diversity (D) 0 0 27 18 Joining (J) 5 4 6 19 VDJ Combinations 40 x 5 = 200 30 x 4 = 120 65 x 27 x 6 = 10,530 20 21 TOTAL GENE COMBINATIONS (200 + 120) x 10,530 = 3,369,600 22 23 24 25 26

The number of genes may look very little... but the possible combinations are staggering! Back Fwd JABSOM John A. Burns School of Medicine e-Learning e-Learning for Basic Sciences FOUR DIVERSITY 1 2 3 4 5 3. Explain antibody diversity from 6 somatic recombination. QUICK REVIEW Think 7 a. The number of gene segments is limited; however, it produces a 8 Fast! 2. Which of the following is NOT true of diverse pool of antibodies. 9 Answer these quick questions how heavy and light chain variable b. The number of gene segments 10 before you move on... region genes are formed? is limited; therefore, the pool of 11 antibodies is limited. a. Formation occurs in the bone 12 marrow. c. The number of gene segments is 13 b. Formation occurs during B-cell unlimited; however, the pool of 14 1. The difference between heavy and development. antibodies is limited. light chain genes is: 15 c. Once a B-cell forms a functional d. The number of gene segments is a. heavy chains lack diversity region antibody, that B-cell can produce unlimited; therefore, the pool of 16 genes. antibodies is infinite. antibodies with different C regions. 17 b. light chains lack diversity region d. Once a B-cell forms a functional 18 genes. antibody, that B-cell can switch to 19 c. light chains have constant region different V genes. genes. 20 d. there is no difference. 21 22 23 24 25 26

This is the last review of the module. Great job! Back Fwd JABSOM John A. Burns School of Medicine e-Learning e-Learning for Basic Sciences

1 2 3 4 5 6 7 8 9 10 11 RESOURCES 12 13 14 15 16 17 Congratulations 18 on completing the module! 19 The following two pages are the 20 summary and glossary to help 21 you review concepts. 22 23 24 25 26

Back Fwd JABSOM John A. Burns School of Medicine e-Learning e-Learning for Basic Sciences SUMMARY 1 2 3 4 5 6 One :: General Structure Two :: Isotypes Three :: Function Four :: Diversity 7 Identify the Parts of an Antibody Identify Antibody Isotypes Match Antibody Functions With Isotypes Explain Antibody Diversity 8 9 1. An antibody is a Y-shaped 1. The heavy and light chain isotypes are Antibody functions include: 1. Somatic recombination is also known 10 glycoproteins consisting of four as V(D)J recombination referring to Light Chain Heavy Chain 1. Antibody-dependent cell-mediated 11 polypeptide chains linked covalently cytotoxicity (ADCC) the variable (V), diversity (D), and by disulfide bonds. 1. kappa (κ) 1. alpha (α) joining (J) region genes. 12 2. Antigen binding 2. An antibody is composed of two light 2. lambda (λ) 2. gamma (γ) 2. Light chains lack diversity genes. 13 3. B-cell antigen reception (mature/ and heavy chains that both have 3. delta (δ) 3. Heavy and light chain variable 14 constant and variable regions. naïve) 4. epsilon (ε) region genes are randomly formed 15 3. Pepsin cleaves an antibody into one 4. B-cell antigen eceptionr (memory) in the bone marrow during B-cell 5. mu (μ) 16 F(ab)2 and several Fc fragments. 5. Classical complement pathway development; however, once a B-cell 2. The three general immunoglobulin 17 3. Papain cleaves an antibody into two forms a functional antibody, it can structures are the monomer, dimer, 6. Opsonization Fab, and one Fc fragments. only make that exact antibody. 18 and the pentamer. 7. Placental transport 4. The number of antibody gene 19 3. J-chains form dimers and pentamers; 8. Triggers mast cell degranulation segments is limited; however, it 20 secretory pieces attach to dimers produces a diverse pool of antibodies. passing through epithelial cells. 21 22 23 24 25 26

Back Fwd JABSOM John A. Burns School of Medicine e-Learning e-Learning for Basic Sciences GLOSSARY 1 2 allergen: an antigen that induces allergic cytotoxicity: the quality of being toxic to : blood cells that engulf and proteolysis: the breakdown of proteins reactions. a cell. digest antigens. into peptides and amino acids. 3 Proteolytically (adj.) 4 antibody: (or immunoglobulin, Ig) a framework region: part of the variable mast cell degranulation: when mast Y-shaped glycoprotein molecule found region that is structurally similar. cells release granules and hormonal secretory piece: a polypeptide that 5 in blood or bodily fluids of humans and mediators that induce allergic reactions. attaches to a dimer (IgA) when it passes 6 other vertebrates; used by the immune heavy chain: the larger polypeptide through epithelial cells in mucosal areas. 7 system to find and destroy antigens. chain that composes an antibody. opsonization: when an antibody acts as a binding enhancer for antigens to be somatic recombination: (or V(D)J 8 humoral response: an immune system Antibody-Dependent Cell Cytotoxicity engulfed by a macrophage. recombination) the process for 9 (ADCC): the cytotoxicity of certain response involving antibodies. generating antibody diversity. lymphocytes that attack and destroy a papain: a cysteine protease, commonly 10 hypervariable region: part of the target cell bound by IgG. found in papaya, that digest proteins variable region: a subdivision of a heavy 11 variable region that is extremely diverse; into fragments. or light chain that has different amino antigen: a substance that binds to an determines antigen specificity. acid sequences; responsible for antigen 12 antibody. pathogen: a disease-causing recognition and binding. 13 immunoglobulin (see antibody) microorganism. 14 B-cells: white blood cells that make V(D)J recombination (see somatic isotype: the class of an antibody light or antibodies and are part of the humoral pepsin: a digestive protease created by recombination) 15 heavy chain. stomach cells that degrade proteins into immune response. 16 fragments. J-chain: (or Joining chain) a protein classical complement pathway: a 17 produced by B-cells and plasma cells biochemical cascade consisting of a placental transport: when IgG transports that connects a monomer to form a 18 number of blood proteins which leads to across the placenta from mother to dimer or pentamer. 19 the killing of pathogens. fetus. 20 light chain: the smaller polypeptide constant region: a subdivision of a heavy protease: an enzyme that breaks down chain that composes an antibody. 21 or light chain that has the same amino proteins. acid sequences. 22 23 24 25 26 HIT Esc to exit FULL SCREEN in Adobe Acrobat