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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    Description

    Explore the intricate structure of the B-cell receptor (BCR) and its complex with signaling proteins. This quiz delves into the composition of BCRs, including the roles of heavy and light chains, and the impact of mRNA processing on receptor forms. Test your knowledge on how these components work together for immune response.

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