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Lecture 2 Lecture 2 Antigens, Receptors and Antigens, Receptors and Immunoglobulins Immunoglobulins

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  • Lecture 2Antigens, Receptors and Immunoglobulins

  • Antigenic Determinants (Epitopes)

  • What is an antibody?Product of adaptive immunityMade specifically to bind a unique antigenic epitope (also called an antigenic determinant)Possesses an antigen binding siteA product of the Plasma cellMembers of the class of proteins called immunoglobulins

  • Receptor-Epitope Interactions and AffinityMost biological systems can be viewed in terms of interactions between receptors and epitopes (hand and glove).Specificity of the interaction between the receptor and epitope is determined by the amino acid sequence of the receptor (tailoring the glove).If the glove is too big, the glove falls off.If the glove is too small, you cant get your hand into it.If the glove is missing fingers

  • Binding of the epitope in the antigen binding siteGOOD FITantibody combining siteantigen determinant

  • Basic Immunoglobulin Structure

  • The Prototype Immunoglobulin MoleculeHeavy Chains (five types: Light Chains (two types: andFab fragmentFc fragmentConstant and variable regionsCarbohydrateDisulfide linkagesFabFcVHCH1CH2CH3VLCL

  • Immunoglobulin G (IgG)2 Heavy and 2 Light chains2 Fab and 1 Fc fragment4 Subclasses (IgG1, IgG2, IgG3, IgG4) Mol. Wt. 150,000 ~70-75% of serum immunoglobulin.The major antibody of the secondary immune responseChange in affinity with time

  • Immunoglobulin M (IgM)10 Heavy and 10 Light chains10 Fab and 5 Fc fragmentsMol. Wt. ~900,000
  • Immunoglobulin A (IgA)Monomeric- Serum IgA~15-20% of serum immunoglobulins2 Heavy and 2 Light 2 Subclasses (IgA1 and IgA2)Found in serum

  • Secretory Immunoglobulin A (sIgA)4 heavy chains and 4 light chains (dimeric)J-Chain and secretory componentThe major immunoglobulin of secretionsNot found in serumSecretory ComponentJ-Chain

  • Immunoglobulin E (IgE)2 Heavy and 2 Light chainsMol. Wt. ~190,000 Trace serum proteinNote CH4 region on H chainAssociated with atopic or anaphylactic hypersensitivityMay play role in immunity to helminthic parasitesCH4

  • Immunoglobulin D (IgD) 2 heavy and 2 light chains
  • Take Home LessonsWhat is the basic immunoglobulin structure?What are the characteristics or features of the various fragments of the immunoglobulin molecule?How is the specificity of an antibody defined by the amino acid sequence of the immunoglobulin molecule?What features distinguish each immunoglobulin class?

    Study GuideHow are antigenic determinants formed?An immune response to a single microorganism represents the collection of all of the immune responses to all of the immunogenic epitopes that comprise that microorganism.Can you imagine how an immune response to one microorganism might react with another microorganism?Study GuideThis is an important concept.Study GuideWhat constitutes a good fit in an antigen binding site?How does antibody affinity relate to fit?What are the forces that are attractive and repulsive?What is actually "fitting" into the combining site?Study GuideCan you describe the major regions of an immunoglobulin molecule?What distinguishes the immunoglobulin classes from one another?What is shared between classes?What is the significance of the variable regions?What is the significance of the Fab, the Fc, disulfide linkages?

    Study GuideWhat is the function of the J chain?We will talk more about this immunoglobulin in the Spring term in the Salivary Gland Course.This immunoglobulin is critical in the protection of mucosal surfaces.What is unique about the secretory component?Where else have you seen the J chain? What is its role?We will have a separate lecture on the role of IgE in atopic hypersensitivity.What is the importance of the CH4 domain of the heavy chain?