BLOCK 3: IMM: (3.4) ANTIBODIES - PART 3
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BLOCK 3: IMM: (3.4) ANTIBODIES - PART 3

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Questions and Answers

What is required for the B-cell receptor to be functional?

  • Association with Ig alpha and beta chains. (correct)
  • Presence of only the immunoglobulin molecule.
  • Phosphorylation of the immunoglobulin alone.
  • Absence of cytoplasmic signaling tails.
  • Why is the cytoplasmic tail important for the B-cell receptor?

  • It is essential for intracellular signaling. (correct)
  • It prevents the receptor from undergoing apoptosis.
  • It acts as a ligand for antigen binding.
  • It provides structural support to the receptor.
  • Which of the following statements about secreted antibodies is correct?

  • They require the same processing mechanism as B-cell receptors.
  • They only have a membrane-bound form, no secreted form.
  • They are produced by a random process without molecular steps.
  • They arise from a distinct pattern of heavy chain RNA processing. (correct)
  • What distinguishes the membrane-bound form of immunoglobulin M from the secreted form?

    <p>The inclusion of a hydrophobic anchor sequence.</p> Signup and view all the answers

    In the context of B-cell activation, what role do ITAMs play?

    <p>They facilitate downstream signaling upon receptor activation.</p> Signup and view all the answers

    What does it mean when referring to the B-cell receptor complex?

    <p>It constitutes the complete structure needed for B-cell activation.</p> Signup and view all the answers

    Which aspect of RNA processing is emphasized for understanding B-cell antibodies?

    <p>Alternative splicing mechanisms for coding regions.</p> Signup and view all the answers

    What aspect of B-cell activation is planned to be discussed in the next class?

    <p>The differentiation of B-cells into plasma cells.</p> Signup and view all the answers

    What does the SC region in B-cell receptors indicate?

    <p>It stands for the secretion coding sequence.</p> Signup and view all the answers

    How does the transcription of heavy chain RNA influence the form of the B-cell receptor?

    <p>It depends on where the RNA transcript is cleaved.</p> Signup and view all the answers

    What is the role of the membrane coding (MC) region in B-cell receptors?

    <p>To provide a hydrophobic segment for membrane insertion.</p> Signup and view all the answers

    What occurs when the cleavage happens after the membrane coding region during RNA processing?

    <p>The transmembrane form of the receptor is produced.</p> Signup and view all the answers

    Which polyadenylated site leads to the production of the secreted form of the antibody?

    <p>Polyadenylated mu S site</p> Signup and view all the answers

    What happens if the hydrophobic membrane coding region is removed during RNA processing?

    <p>The antibody will be secreted rather than attached to the membrane.</p> Signup and view all the answers

    Which process determines whether a B-cell receptor is secreted or remains on the cell membrane?

    <p>Alternative mRNA processing.</p> Signup and view all the answers

    What structural feature allows the B-cell receptor to be integrated into the cell membrane?

    <p>A hydrophobic membrane coding region.</p> Signup and view all the answers

    Which immunoglobulin isotype forms pentamers in its soluble secreted form?

    <p>IgM</p> Signup and view all the answers

    What is a major effector function of immunoglobulin G (IgG)?

    <p>Facilitating complement activation</p> Signup and view all the answers

    Which heavy-chain isotype is associated with the opsonization process?

    <p>IgG2</p> Signup and view all the answers

    Which immunoglobulin isotype is primarily produced as dimers and secreted at mucosal surfaces?

    <p>IgA</p> Signup and view all the answers

    What characteristic feature differentiates membrane-bound immunoglobulins from their secreted forms?

    <p>Inclusion of a hydrophobic membrane coding region</p> Signup and view all the answers

    Which immunoglobulin isotype has a structure defined as a monomer in both its membrane-bound and secreted form?

    <p>IgD</p> Signup and view all the answers

    Which statement regarding N-linked carbohydrate groups in immunoglobulins is accurate?

    <p>Distribution of N-linked carbohydrates varies among different immunoglobulin isotypes.</p> Signup and view all the answers

    What is the significance of opsonization in immune response?

    <p>It enhances the ability of antibodies to facilitate phagocytosis.</p> Signup and view all the answers

    What unique structural feature distinguishes IgM from other immunoglobulins?

    <p>Pentameric form held by J chain</p> Signup and view all the answers

    Which function is primarily attributable to the pentameric structure of IgM?

    <p>Ability to attach to multiple identical epitopes</p> Signup and view all the answers

    What is the significance of the hinge region in IgG?

    <p>It allows flexibility for optimal antigen accommodation.</p> Signup and view all the answers

    How do the subclasses of IgG differ from one another?

    <p>Relative lengths of hinge regions and disulfide bonds</p> Signup and view all the answers

    What is the main consequence of isotype switching in B cells?

    <p>Increased antibody diversity without changing specificity.</p> Signup and view all the answers

    What unique property does IgG4 possess compared to other IgG subclasses?

    <p>Functionally monovalent in circulation</p> Signup and view all the answers

    Which enzyme is primarily responsible for initiating the isotype switching process?

    <p>Activation-induced cytidine deaminase (AID)</p> Signup and view all the answers

    Which of the following statements is true regarding the synthesis of dimeric IgA?

    <p>Dimeric IgA associates with the J chain to stabilize its structure.</p> Signup and view all the answers

    In what way do memory B cells undergo isotype switching?

    <p>Induced by T cell cytokines during secondary exposures.</p> Signup and view all the answers

    What occurs during gene rearrangement in B cells before immunoglobulin expression?

    <p>Restructuring of light and heavy chain genes</p> Signup and view all the answers

    What type of immunoglobulin is predominantly produced during the primary immune response?

    <p>IgM</p> Signup and view all the answers

    The lack of a hinge region in IgM contributes to which characteristic?

    <p>Structural rigidity but enhanced binding sites</p> Signup and view all the answers

    What does the 'elbow' within the Fab portion of IgG allow?

    <p>Flexibility to adapt binding orientation</p> Signup and view all the answers

    How many potential antigen-binding combinations are possible due to the genetic arrangement of immunoglobulin genes?

    <p>More than 26 million</p> Signup and view all the answers

    Which immunoglobulin type appears to have the greatest number of antigen-binding sites?

    <p>IgM</p> Signup and view all the answers

    What is the role of switch regions in isotype switching?

    <p>To provide a specific sequence for nicks to form.</p> Signup and view all the answers

    Which immunoglobulin class does the constant region epsilon (ε) define?

    <p>IgE</p> Signup and view all the answers

    What is the role of the J chain in the structure of immunoglobulins?

    <p>To stabilize pentameric and dimeric forms</p> Signup and view all the answers

    What characteristic of IgG allows it to interact optimally with C1q and other effector molecules?

    <p>The wagging of its Fc tail</p> Signup and view all the answers

    Which immunoglobulin class is associated with mucosal immunity?

    <p>IgA</p> Signup and view all the answers

    During isotype switching, what happens to the intervening DNA between switch regions?

    <p>It is excised and forms a nonfunctional circle.</p> Signup and view all the answers

    What distinguishes the various immunoglobulin classes from one another?

    <p>The heavy chain isotypes they express.</p> Signup and view all the answers

    Which statement best describes the relationship between heavy chain genes and immunoglobulin isotypes?

    <p>Different heavy chain genes determine the immunoglobulin isotype.</p> Signup and view all the answers

    What happens to B cells during secondary immune responses compared to primary responses?

    <p>They generate higher-affinity antibodies faster, mainly IgG.</p> Signup and view all the answers

    What chromosome encodes the gene clusters for heavy chains?

    <p>Chromosome 14</p> Signup and view all the answers

    Study Notes

    B-cell Receptor Structure

    • The B-cell receptor (BCR) is a transmembrane protein composed of an immunoglobulin molecule and associated signaling proteins.
    • The immunoglobulin molecule consists of a heavy chain and a light chain, both with variable and constant regions.
    • The heavy chain has a secretion coding (SC) region followed by a membrane coding (MC) region.
    • The SC region is responsible for the secreted form of the BCR, while the MC region is responsible for the membrane-bound form.
    • Alternative mRNA processing determines whether the BCR is secreted or membrane-bound.
    • The polyadenylation site after the MC region (PA mu M) results in a transmembrane BCR.
    • The polyadenylation site before the MC region (PA mu S) results in a secreted BCR.

    B-cell Receptor Complex

    • The BCR complex is composed of the BCR itself (immunoglobulin molecule), Igα and Igβ signaling proteins.
    • The BCR complex is responsible for intracellular signaling upon antigen binding.
    • The cytoplasmic tails of Igα and Igβ contain immunoreceptor tyrosine-based activation motifs (ITAMs).
    • ITAMs are phosphorylated upon antigen binding, triggering downstream signaling pathways.

    Secretion of Antibodies

    • Secretion of antibodies is another example of alternative mRNA processing.
    • Alternative splicing of the heavy chain mRNA results in a secreted form of the antibody.
    • The textbook provides an example of IgM, which can be either membrane-bound or secreted.
    • The secreted form of IgM lacks the MC region, allowing it to be released from the cell.

    Immunoglobulin Isotypes

    • Different immunoglobulin isotypes are defined by their heavy chain constant region, indicated by Greek letters.
    • Isotypes also differ in their N-linked carbohydrate groups.
    • All immunoglobulins are monomers in their membrane-bound form.
    • IgD, IgE and IgG are monomers in their soluble, secreted form.
    • IgA exists as monomers and dimers, while IgM exists mainly as pentamers.

    Immunoglobulin Isotype Functions

    • Each isotype has specialized functions:
      • Major functions are represented by dark red shading
      • Lesser functions are represented by dark pink
      • Minor functions are represented by pale pink.
      • Opsonization refers to the ability of the antibody to facilitate phagocytosis.
      • Antibodies that activate the complement system indirectly cause opsonization through complement activation.

    Isotype Switching

    • Involves somatic recombination events that attach different heavy-chain constant region genes to the existing variable region exon, also known as class switching.
    • This occurs through recombination between switch regions (S) with deletion of DNA between them.
    • Switch regions are targeted by Activation-induced cytidine deaminase (AID), causing nicks in DNA strands.
    • AID and the repair process of damaged DNA are essential for both somatic hypermutation and isotype switching.

    Isotype Switching Mechanism

    • The nicks in DNA facilitate recombination between the switch regions leading to the excision of intervening DNA and the juxtaposition of the rearranged variable region with a different constant region gene.
    • The first switch in a clone of B cells is from the μ isotype to another isotype.
    • Subsequent switching to other isotypes can occur later.

    Isotype Switching in Memory B Cells

    • Antibodies produced by memory B cells that have experienced prolonged or repeated exposure to the same epitope might undergo isotype switching, induced by T cell cytokines.
    • The availability of multiple isotypes with the same specificity allows the humoral response to activate various mechanisms against the same epitope.
    • Serial reactivation of memory B cells allows the isotype switch to occur during each restimulation.
    • IgM is the predominant isotype in primary responses, while secondary responses are mostly IgG with significant amounts of IgA and IgE.

    Immunoglobulin Gene Clusters

    • Gene clusters encoding κ (kappa) light chains are located on chromosome 2.
    • Gene clusters encoding λ (lambda) light chains are located on chromosome 22.
    • The heavy chain gene cluster is located on chromosome 14.
    • The potential antigen-binding combinations are greater than 26 million.

    Immunoglobulin Basic Structure

    • Light chains, termed κ (kappa) or λ (lambda) are on chromosomes 2 & 22, respectively.
    • Five types of heavy chains are encoded on chromosome 14:
      • Mu (μ)
      • Delta (δ)
      • Gamma (γ)
      • Epsilon (ε)
      • Alpha (α)
    • Isotypes are genetically different forms of light chains (κ & λ) and of heavy chains (μ, δ, γ, ε, & α).
    • Immunoglobulin class or subclass is determined by the heavy chain isotype.

    Immunoglobulin Class Structure

    • IgM is secreted as a pentamer of immunoglobulin monomers.
    • The IgM pentamer is held together by a polypeptide called the J chain for "joining chain".
    • Monomers are cross-linked by disulfide bonds to each other and to the J chain.
    • The lack of a hinge region in IgM monomer makes the molecule less flexible than others, but this is compensated by the pentamer having five times as many antigen-binding sites as IgG.
    • With pathogens possessing multiple identical epitopes on their surface, IgM can attach with several binding sites simultaneously.

    IgA Dimer Formation

    • IgA is synthesized as a dimer in mucosal lymphoid tissue, associated with the same J chain found in pentameric IgM.
    • In dimeric IgA, monomers are disulfide bonded to the J chain but not to each other.

    IgG Flexibility

    • The most flexible part of the IgG molecule is its hinge.
    • The hinge allows the Fab arms to wave and rotate, accommodating the antibody to the orientation of epitopes on pathogen surfaces.
    • The “elbow” within the Fab adds more flexibility, allowing variable domains to bend with respect to constant domains.
    • The “wagging” of the Fc tail allows IgG molecules bound to antigen to accommodate the binding of C1q and other effector molecules.

    IgG Subclasses

    • The four IgG subclasses have different and complementary functions.
    • Differences in hinge structure, number of disulfide bonds, and amino acid sequences, particularly glycine and proline residues, influence hinge flexibility.

    IgG4 Functional Monovalency

    • IgG4 is synthesized in a form that has two heavy chains, two light chains, and two identical antigen-binding sites.
    • Molecules of IgG4 can interact and exchange one heavy chain and its associated light chain in circulation.
    • This property results in most IgG4 molecules in circulation having TWO different binding sites for antigen.
    • Therefore, they interact with a pathogen or a protein antigen through only one binding site.

    Immunoglobulin Gene Rearrangement

    • Before immunoglobulin light-chain (κ or λ) and heavy-chain genes can be expressed, rearrangements of gene segments are needed to produce exons encoding V regions.
    • After rearrangement, the genes are transcribed into primary transcripts containing both exons and introns.
    • The introns are spliced out, producing mRNAs that translate into kappa or lambda light chains and mu heavy chains.
    • These chains assemble inside the cell and are expressed as membrane-bound IgM at the cell surface.

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