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Pharm immuno5-6serv adaptive immune response ag-ab


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Pharm immuno5-6serv adaptive immune response ag-ab

  1. 1. LECOM-Pharmacy Immunology 5 & 6 Adaptive (acquired) immune response Antigen & Antibody Dr. Saber Hussein
  2. 2. Objectives <ul><li>Define antigenicity and immunogenicity </li></ul><ul><li>Four characteristics of immuogenic molecule ( requirements for immunogenicity) </li></ul><ul><ul><li>Foreignness </li></ul></ul><ul><ul><li>High molecular weight </li></ul></ul><ul><ul><li>Chemical complexity </li></ul></ul><ul><ul><li>Degradability </li></ul></ul><ul><li>Define haptens and their functions </li></ul><ul><li>Define antigenic determinants </li></ul><ul><li>Capture of protein antigens by antigen presenting cells </li></ul><ul><li>Antigen recognized by T lymphocytes </li></ul><ul><li>Antigens recognized by B lymphocytes </li></ul>
  3. 3. Learning Objectives <ul><li>Basic structure of Abs in relation to specificity & diversity </li></ul><ul><li>Variable & constant regions of light & heavy chain </li></ul><ul><li>Biological & chemical characteristics of the 5 classes of Ab </li></ul><ul><li>Compare polyclonal & monoclonal Ab </li></ul><ul><li>Three characteristics of primary Ag-Ab reaction </li></ul><ul><li>The forces that foster the primary Ag-Ab reaction </li></ul><ul><li>Affinity & avidity of Abs </li></ul><ul><li>Secondary Ag-Ab reaction; lattice formation </li></ul>
  4. 4. Objectives <ul><li>9. Know the role of receptors in the recognition of antigen in the adaptive immune system: </li></ul><ul><ul><li>Antibodies as receptors of B lymphocytes </li></ul></ul><ul><ul><li>T cell receptor (TCR) for antigens </li></ul></ul><ul><li>10. Development of immune repertoires </li></ul><ul><ul><li>Maturation of lymphocytes </li></ul></ul><ul><ul><li>Production of diverse antigen receptors </li></ul></ul><ul><ul><li>Maturation and selection of B lymphocytes </li></ul></ul><ul><ul><li>Maturation and selection of T lymphocytes </li></ul></ul>
  5. 5. Antigenicity & Immunogenicity <ul><li>Antigenicity : </li></ul><ul><ul><li>The ability to bind an Ab or an activated T cell </li></ul></ul><ul><ul><li>Every immunogen is an antigen, BUT not every antigen is an immunogen </li></ul></ul><ul><li>Immunogenicity : </li></ul><ul><ul><li>Ability to elicit immune response </li></ul></ul><ul><ul><li>Only proteins can induce cellular immunity </li></ul></ul><ul><ul><li>Humoral immunity can be induced by: </li></ul></ul><ul><ul><ul><li>Proteins </li></ul></ul></ul><ul><ul><ul><li>Lipopolysaccharides </li></ul></ul></ul><ul><ul><ul><li>Nucleic acids </li></ul></ul></ul><ul><ul><ul><li>Other substances </li></ul></ul></ul>
  6. 6. Features of an Immunogen <ul><li>High molecular weight </li></ul><ul><li>Chemical complexity </li></ul><ul><li>Solubility or biodegradability </li></ul><ul><li>Foreignness or nonself </li></ul>
  7. 7. Ab cross-reactions with different Ags <ul><li>Abs react most strongly with homologous Ag </li></ul><ul><li>Sometimes they cross-react with other Ags </li></ul><ul><li>Cross-reaction </li></ul><ul><ul><li>The reaction between an Ag and an Ab that was generated against a different Ag but with some similarity with the cross-reacting Ag </li></ul></ul><ul><li>Cross-reactions are related to chemical structure of Ags: </li></ul><ul><ul><li>i. Chemical nature of hapten’s groups </li></ul></ul><ul><ul><li>ii. Position of substitutions </li></ul></ul><ul><ul><li>iii. Size of substituted groups </li></ul></ul><ul><ul><li>iv. Charge </li></ul></ul><ul><ul><li>v. Stereoisomerism </li></ul></ul>
  8. 8. Haptens, Antigenic Determinants (Epitopes) <ul><li>Ag has 2 functional regions: </li></ul><ul><ul><li>Hapten </li></ul></ul><ul><ul><li>Carrier </li></ul></ul><ul><li>Epitopes are immunologically active portions of Ag </li></ul><ul><li>Epitopes on an Ag are recognized by B cells and T cells </li></ul><ul><li>Antigenic determinants serve as fingerprint of macromolecules </li></ul><ul><li>Size of an epitope is determined by the size of the Ab’s Ag-binding site </li></ul><ul><li>Size of recognizable epitope by an Ab: </li></ul><ul><ul><li>6 sugar residues </li></ul></ul><ul><ul><li>15-20 amino acids (Some linear epitopes are as small as 5 aas) </li></ul></ul>Ab Carrier Hapten
  9. 9. Haptens &Antigenic Determinants <ul><li>Haptens </li></ul><ul><li>Usually small molecules </li></ul><ul><li>Not immunogenic by themselves </li></ul><ul><li>Always antigenic with a specific Ab </li></ul><ul><li>Immunogenic when combined with a carrier molecule (large) </li></ul><ul><li>Simple hapten: only 1 antigenic determinant </li></ul><ul><li>Complex hapten: > 2 antigenic determinants </li></ul><ul><li>Antigenic Determinants </li></ul><ul><li>Small part of the molecule </li></ul><ul><ul><li>Few amino acids </li></ul></ul><ul><ul><li>A short carbohydrate moiety- few sugars </li></ul></ul><ul><li>Must be accessible to be functional </li></ul><ul><li>Charge & polarity </li></ul><ul><li>Conformation dependent </li></ul>
  10. 10. Ag recognized by T lymphocytes <ul><li>T lymphocytes recognize only protein antigens </li></ul><ul><li>Proteins must be presented in the form of short peptides </li></ul><ul><li>They must be presented by an APC with the appropriate MHC molecule: </li></ul><ul><ul><li>MHC I presents antigen to the cytotoxic T cell </li></ul></ul><ul><ul><li>MHC II presents antigen to the helper T cell </li></ul></ul>
  11. 11. Antigens recognized by B lymphocytes <ul><li>T-cell in dependent route of antigen recognition: </li></ul><ul><ul><li>B lymphocytes recognize certain antigens without the help of the T H cell </li></ul></ul><ul><ul><li>These include: </li></ul></ul><ul><ul><ul><li>Lipopolysaccharides </li></ul></ul></ul><ul><ul><ul><li>Nucleic acids: DNA & RNA </li></ul></ul></ul><ul><ul><li>No long term immunity results through this route </li></ul></ul><ul><ul><li>Only IgM is produced </li></ul></ul><ul><ul><li>No memory cells </li></ul></ul>
  12. 12. Antigens recognized by B lymphocytes <ul><li>T-cell dependent route: </li></ul><ul><ul><li>Recognizes protein antigens </li></ul></ul><ul><ul><li>Long term immunity </li></ul></ul><ul><ul><li>IgG is produced by class switching </li></ul></ul><ul><ul><li>Memory cells </li></ul></ul>
  13. 13. Antigens recognized by B lymphocytes <ul><li>T-cell dependent </li></ul><ul><li>Recognizes protein antigens </li></ul><ul><li>Long term immunity </li></ul><ul><li>IgG is produced by class switching </li></ul><ul><li>Memory cells </li></ul><ul><li>T-cell in dependent </li></ul><ul><li>Recognizable Ags: </li></ul><ul><ul><ul><li>Lipopolysaccharides </li></ul></ul></ul><ul><ul><ul><li>Nucleic acids: DNA & RNA </li></ul></ul></ul><ul><li>No long term immunity results through this route </li></ul><ul><li>Only IgM is produced </li></ul><ul><li>No memory cells </li></ul>
  14. 14. Antigen Capture and Presentation to Lymphocytes <ul><li>A model of how a T cell receptor (TCR) recognizes a complex of a peptide antigen displayed by a major histocompatibility (MHC) molecule </li></ul><ul><ul><li>MHC molecules are expressed on antigen-presenting cells and function to display peptides derived from protein antigens </li></ul></ul><ul><ul><li>Peptides bind to the MHC molecules by anchor residues , which attach the peptides to pockets in the MHC molecules </li></ul></ul><ul><ul><li>The TCR of every T cell recognizes some residues of the peptide and some (polymorphic) residues of the MHC molecule </li></ul></ul>Fig. 3-1
  15. 15. The capture and display of microbial antigens <ul><li>Microbes enter the body </li></ul><ul><ul><li>through an epithelium and are captured by antigen-presenting cells resident in the epithelium </li></ul></ul><ul><ul><li>enter lymphatic vessels or </li></ul></ul><ul><ul><li>blood vessels </li></ul></ul><ul><li>The microbes and their antigens are transported to peripheral lymphoid organs </li></ul><ul><ul><li>the lymph nodes, </li></ul></ul><ul><ul><li>the spleen, </li></ul></ul><ul><ul><ul><li>where protein antigens are displayed for recognition by T lymphocytes </li></ul></ul></ul>Fig. 3-2
  16. 16. The capture and presentation of protein antigens by dendritic cells <ul><li>Immature dendritic cells in the epithelium capture microbial antigens by surface receptors and leave the epithelium </li></ul><ul><li>The dendritic cells migrate to draining lymph nodes, being attracted there by chemokines produced in the nodes </li></ul><ul><li>During their migration, and in response to the microbe, the dendritic cells mature </li></ul><ul><li>Mature DC express high level MHC & costimulators </li></ul><ul><li>In the lymph nodes, the dendritic cells present antigens to naive T cells </li></ul>Fig 3-4 Langerhans cells
  17. 17. Properties of MHC molecules and genes <ul><li>Some of the important features of MHC molecules are listed, with their significance for immune responses </li></ul>Fig 3-8
  18. 18. Role of MHC in Antigen Presentation to T Cells <ul><li>Ag processing </li></ul><ul><ul><li>The event whereby the Ag is prepared to be presented to lymphocytes in a form they can recognize </li></ul></ul><ul><ul><li>It includes fragmentation of the protein Ag into small peptides in the macrophage and the presentation to T cells </li></ul></ul><ul><li>Ag-presenting cells (APCs) bind peptide Ags to their MHC II and present it to the CD4 + helper T cells </li></ul><ul><li>APCs present peptides to CD8 + cytotoxic T cells with their MHC I </li></ul><ul><li>Ag-presenting cells (APCs) include macrophages and other cells </li></ul>
  19. 19. Major Histocompatibility Complex (MHC) m
  20. 20. MHC Restriction of T Cells <ul><li>The process by which the MHC controls interactions between immune cells </li></ul><ul><li>It involves the recognition of foreign antigens in association with class I or II molecules </li></ul><ul><li>The following reactions are MHC-restricted: </li></ul><ul><ul><li>Antigen presentation </li></ul></ul><ul><ul><li>T- and B-cell cooperation </li></ul></ul><ul><ul><li>Cytotoxic T-cell interaction with target cells </li></ul></ul><ul><ul><ul><li>Malignant cells </li></ul></ul></ul><ul><ul><ul><li>Viral infected cell </li></ul></ul></ul>
  21. 21. What Regions of HLA Complex Encode MHC I & MHC II? <ul><li>Coding Regions: </li></ul><ul><li>MHC-I coding region: </li></ul><ul><ul><li>HLA-A, HLA-B and HLA-C </li></ul></ul><ul><li>MHC-II coding region: </li></ul><ul><ul><li>HLA-D [ DN, DO, DP , DQ & DR ] </li></ul></ul>
  22. 23. What kind of T cell do we see here? Antigen-MHC Class II Complex
  23. 24. Fig 4-1 : Properties of antibodies and T cell antigen receptors (TCRs) <ul><li>Antibodies may be expressed as membrane receptors or secreted proteins </li></ul><ul><li>TCRs only function as membrane receptors </li></ul><ul><li>When Ig or TCR molecules recognize antigens, signals are delivered to the lymphocytes by proteins associated with the antigen receptors </li></ul><ul><li>The antigen receptors and attached signaling proteins form the B cell receptor (BCR) & TCR complexes </li></ul><ul><li>Single antigen receptors are shown recognizing antigens, </li></ul><ul><li>Signaling requires the cross-linking of two or more receptors by binding to adjacent antigen molecules </li></ul>
  24. 25. Fig 4-1 CD4,8 Fig 4-1 T cell B cell
  25. 26. Fig 4-1   : zeta )
  26. 27. Fig 4-2: The structure of antibodies <ul><li>Schematic diagrams of a secreted IgG (A) and a membrane form of IgM (B) illustrate the domains of the heavy and light chains and the regions of the proteins that participate in antigen recognition and effector functions </li></ul><ul><li>N and C refer to the amino-terminal and carboxy-terminal ends of the polypeptide chains, respectively </li></ul>
  27. 28. Fig 4-2
  28. 29. Fig 4-3: Features of the major isotypes (classes) of antibodies <ul><li>The table summarizes some important features of the major antibody isotypes of humans. </li></ul><ul><li>Isotypes are classified on the basis of their heavy chains </li></ul><ul><li>Each isotype may contain either  or  light chain </li></ul><ul><li>Each of the 5 classes differ in their locations in our body and how they stimulate the innate system to remove antigen </li></ul><ul><li>The schematic diagrams illustrate the distinct shapes of the secreted forms of these antibodies </li></ul><ul><li>IgA consists of two subclasses : IgA1 and IgA2 </li></ul><ul><li>IgG consists of 4 subclasses : IgG1, IgG2, IgG3, & IgG4 </li></ul><ul><li>The serum concentrations are average values in normal individuals </li></ul>
  29. 30. Fig 4-3: Features of the major isotypes of Abs Breast-fed neonates get it with the mother’s milk Antiparasitic activity with mother’s milk
  30. 31. Fig 4-3: Features of the major isotypes of Abs Diagnostic for acute infections
  31. 32.                                                                                        
  32. 33. Polyclonal & Monoclonal Abs <ul><li>Polyclonal Abs </li></ul><ul><li>Heterogeneous mix of Abs </li></ul><ul><li>With specificity against the same Ag </li></ul><ul><li>Produced by variety of Ab-producing cells </li></ul><ul><li>They are many clones of cells </li></ul><ul><li>Polyclonal Abs recognize & react against different epitopes on the Ag </li></ul><ul><li>Avidity </li></ul><ul><li>Monoclonal Abs </li></ul><ul><li>Produced by a single clone of cells </li></ul><ul><li>Resultant Abs are identical in all aspects </li></ul><ul><li>Same affinity </li></ul><ul><li>Same binding specificity </li></ul><ul><li>Recognize the same epitope </li></ul><ul><li>They are produced in hybridoma between activated B cells and malignant plasma cells (fusion) </li></ul>
  33. 34. Three dimensional representation of the IgG molecule IgG molecule
  34. 35. IgG <ul><li>IgG digestion with papain produces 3 fragments </li></ul><ul><ul><li>2 identical Fab fragments </li></ul></ul><ul><ul><ul><li>Fab fragments , are capable of binding Ag because they contain the Ag-binding site </li></ul></ul></ul><ul><ul><li>Fc fragment : a fragment composed of H chain only . </li></ul></ul><ul><ul><ul><li>It crystallizes in the cold </li></ul></ul></ul>
  35. 36. Pentameric structure of IgM <ul><li>The structure of IgM is similar to that of IgG except the IgM heavy chain has an extra domain . </li></ul><ul><li>A small, cysteine-rich protein called J chain initiates cross linking of C3 and C4 of </li></ul><ul><ul><li>five IgM monomers to make the circulating, pentameric form of IgM </li></ul></ul>
  36. 37. Dimeric structure of IgA <ul><li>Dimeric IgA held together by </li></ul><ul><ul><li>J chain and </li></ul></ul><ul><ul><li>secretory component </li></ul></ul>J chain Secretory component
  37. 38. Secretory IgA <ul><li>IgA represents 15-20% of serum immunoglobulin </li></ul><ul><li>It constitutes the majority of Ab found in secretions </li></ul><ul><li>Humans have 2 types of IgA: </li></ul><ul><ul><li>IgA1 and IgA2 </li></ul></ul><ul><ul><li>IgA1 is the prominent subclass in serum and is found mainly as monomer </li></ul></ul><ul><ul><li>IgA2 is the prominent Ig in secretions (saliva, gut, respiratory mucus) and occurs as a dimer with two Fc ends of the Abs bound together by a J chain </li></ul></ul><ul><li>Secretion across the mucosa is mediated by a specific secretory component which binds to a cell receptor </li></ul>
  38. 39. IgE <ul><li>IgE is similar to IgG except </li></ul><ul><ul><li>it has an extra constant region domain on the H-chain </li></ul></ul><ul><li>Functions: </li></ul><ul><ul><li>Type I hypersensitivity </li></ul></ul><ul><ul><li>Anti-parasitic </li></ul></ul><ul><ul><li>Degranulation of mast cells </li></ul></ul>
  39. 40. IgD <ul><li>IgD is similar to the structure of IgG. </li></ul><ul><li>Its only known function is as part of the signaling complex of B cells </li></ul>
  40. 41. Primary Ag-Ab reaction <ul><li>The first interaction between Ag & Ab </li></ul><ul><li>Key-lock principle </li></ul><ul><li>Ag-Ab interaction is precise = specific </li></ul><ul><li>Characteristics of Ag-Ab reaction: </li></ul><ul><li>i. Rapid, in seconds </li></ul><ul><li>ii. Independent of electrolytes, salt, buffer </li></ul><ul><li>iii. Not visible </li></ul>
  41. 42. Fig 4-4: Binding of an Ag by an Ab <ul><li>This model of a protein antigen bound to an antibody molecule shows how the antigen-binding site can accommodate soluble macromolecules in their native (folded) conformation . </li></ul><ul><li>The heavy chains (H) of the antibody are red </li></ul><ul><li>L chains: yellow </li></ul><ul><li>Ag is blue </li></ul>
  42. 43. Chemical forces foster Ab-Ag <ul><li>Four noncovalent interactions hold antigenic determinants w/in Ab-binding site: </li></ul><ul><li>Coulombic (electrostatic, ionic) interactions </li></ul><ul><li>Van der Waals forces </li></ul><ul><li>Hydrogen bonds </li></ul><ul><li>Hydrophobic interactions </li></ul>
  43. 44. Secondary Ag-Ab reaction & Secondary response <ul><li>Secondary Ag-Ab reaction : </li></ul><ul><li>The conversion of the invisible primary reactions macroscopically visible ones as in the case of precipitation and agglutination </li></ul><ul><li>Secondary response : </li></ul><ul><li>The immune response which follows a second encounter with a particular Ag </li></ul><ul><li>It is usually stronger ( affinity maturity ) </li></ul>
  44. 45. Lattice formation <ul><li>Occurs when </li></ul><ul><ul><li>Ag-Ab complexes aggregate in form of precipitation in liquid medium - </li></ul></ul><ul><ul><li>Agglutination , including particulate components , other than Ag and Ab, such as cells </li></ul></ul>Ag Ab
  45. 46. Affinity & Avidity <ul><li>Affinity is the strength of Ag-Ab bonds between a single epitope and an individual Ab’s binding site </li></ul><ul><li>Avidity : The binding strength between a multivalent Ab (polyclonal Ab) and a multivalent Ag </li></ul><ul><li>Ag + Ab  Ag..Ab </li></ul><ul><li>K = [Ag..Ab]/[Ag][Ab] </li></ul><ul><li>The higher [Ag..Ab], the larger is K (the associated Ab and Ag), the higher is affinity of the Ab to the Ag. </li></ul><ul><li>K = Equilibrium constant </li></ul><ul><li>= Association constant </li></ul><ul><li>= Ab affinity </li></ul>
  46. 47. Affinity maturity <ul><li>Ag + Ab  Ag..Ab </li></ul><ul><li> K D = [Ag][Ab] / [Ag..Ab] </li></ul><ul><li>The lower the K D ( dissociation constant ) the higher the affinity </li></ul><ul><li>Affinity maturity : after repeated exposure to the Ag the affinity increases </li></ul>
  47. 48. Monoclonal Ab production <ul><li>Immunize animals, rats or mice, with Ag </li></ul><ul><li>When the animals start to make a good Ab response remove their spleens and prepare a cell suspension </li></ul><ul><li>Fuse spleen cells with a myeloma cell line by the addition of polyethylene glycol (PEG), which promotes membrane fusion </li></ul><ul><ul><li>Only a small proportion of the cells fuse successfully </li></ul></ul><ul><li>The fusion mixture is then set up in culture with medium containing “HAT” </li></ul><ul><ul><li>HAT = Mixture of </li></ul></ul><ul><ul><ul><li>Hypoxanthine </li></ul></ul></ul><ul><ul><ul><li>Aminopterin (powerful toxin that blocks a metabolic pathway) </li></ul></ul></ul><ul><ul><ul><li>Thymidine (H & T intermediate metabolites help the cell bypass the pathway when added) </li></ul></ul></ul><ul><ul><li>Spleen cells can grow/survive in HAT </li></ul></ul><ul><ul><li>Myeloma cells are sensitive to HAT because of metabolic defect that prevents them from using the bypass </li></ul></ul><ul><ul><li>HAT culture contains: </li></ul></ul><ul><ul><ul><li>Spleen cells: die naturally in 1-2 weeks </li></ul></ul></ul><ul><ul><ul><li>Myeloma cells: Killed by HAT </li></ul></ul></ul><ul><ul><ul><li>Fused cells (hybridoma): Survive because of immortality of myeloma and HAT-resistance of the spleen cells </li></ul></ul></ul><ul><ul><ul><ul><li>Some produce antibody </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Any wells containing growing cells are tested for the production of the desired Ab (often by solid phase immunoassay) </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Positive ones are cloned by plating out so that there is only one cell in each well </li></ul></ul></ul></ul><ul><ul><ul><ul><li>This produces a clone derived from a single progenitor, which is both: </li></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>Immortal </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>Producer of monoclonal Ab </li></ul></ul></ul></ul></ul>
  48. 49. Humoral Immune Response
  49. 50. B cells produce Abs <ul><li>B cells are specialized white blood cells produced in the bone marrow. </li></ul><ul><li>Each B cell contains multiple copies of one kind of antibody as a surface receptor for antigen. </li></ul><ul><li>The entire population of B cells has the ability to specifically bind to millions of different antigens </li></ul><ul><li>When the antibody on the surface of a B cell binds to an antigen , the cell can be stimulated to undergo proliferation and differentiation. </li></ul><ul><li>This process is called clonal selection . </li></ul>
  50. 51. Clonal selection <ul><li>The cells produced make the same Ab, but become memory cells and plasma cells </li></ul><ul><ul><li>Memory cells insure that subsequent infections by the pathogen receive a more rapid response. </li></ul></ul><ul><ul><li>Plasma cells secrete large amounts of the Ag-specific Ab </li></ul></ul><ul><li>T helper cells are required for the clonal selection of B cells </li></ul><ul><li>Ab secreted by plasma cells forms complexes with free pathogens and their toxic products </li></ul><ul><li>The complexes can: </li></ul><ul><ul><li>inactivate pathogens & </li></ul></ul><ul><ul><li>stimulate other innate systems including </li></ul></ul><ul><ul><ul><li>phagocytes and complement to eliminate the danger from our extracellular fluids </li></ul></ul></ul>
  51. 52. Abs and their diversity <ul><li>An Ab immunoglobulin is a &quot;Y&quot; shaped molecule made up of two identical &quot;light&quot; and &quot;heavy&quot; chains of amino acids. </li></ul><ul><li>The variable region includes the N-terminal 110-130 amino acids of the light and heavy chains, and is responsible for binding to antigen. </li></ul><ul><li>The constant region is the C-terminal end and contains similar amino acids for each class of Ab. </li></ul>
  52. 54. Abs Diversity (con) <ul><li>When a stem cell changes to become a B cell, DNA segments for both heavy (VDJ) and light (VJ) chains are randomly combined. </li></ul><ul><li>Each B cell ends up with functional genes for making one light and one heavy chain coding for an Ab as a membrane-bound receptor. </li></ul><ul><li>Ab specificity depends on the gene fragments used. </li></ul><ul><li>Abs are produced that can react with almost any chemical structure in nature. </li></ul>
  53. 55. The immune system creates billions of different Abs with a limited number of genes by rearranging DNA segments during B cell development , prior to Ag exposure. Mutation can also increase genetic variation in Abs Abs Diversity Heavy chain Light chain
  54. 56. Ab Class switching <ul><li>At first, B cells contain IgM molecules only. </li></ul><ul><li>Class switching occurs after Ag binding , when plasma cells are produced. </li></ul><ul><li>Class switching refers to a DNA rearrangement changing the heavy chain constant gene in memory cells. </li></ul><ul><li>Loss of coding regions for the constant part of the heavy chain causes IgG, IgA, and IgE to be produced. </li></ul>
  55. 57. Ab Class switching to produce IgA