Antigen Recognition in Adaptive Immunity
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Questions and Answers

What are the primary regions that make up the structure of lymphocyte antigen receptors?

  • Extracellular and intracellular regions
  • Variable region and constant region (correct)
  • Functional and structural domains
  • Alpha and beta chains

    • Which hypervariable region of an antibody contains the greatest variability and significantly contributes to antigen binding?

  • Hinge region
  • CDR1
  • CDR2
  • CDR3 (correct)

    • Which type of chains participate in the binding and neutralization of microbes and toxins, but do not take part in effector functions?

  • Heavy chains
  • Light chains (correct)
  • Fc chains
  • Hinge chains

    • What are the sections of an antibody that allow for independent movement of antigen-binding sites?

    <p>Hinge region (C)</p> Signup and view all the answers

    How is the vast diversity of receptor structures in the lymphocyte repertoire primarily generated?

    <p>V(D)J recombination (D)</p> Signup and view all the answers

    What is the concept of the affinity of interaction in the context of antigen-antibody binding?

    <p>The strength with which an antibody binds to an epitope (B)</p> Signup and view all the answers

    Which of the following types of immunoglobulin heavy chains is NOT one of the five classes?

    <p>Beta (D)</p> Signup and view all the answers

    What distinguishes conformational epitopes from linear epitopes?

    <p>The specific structural arrangement of amino acids (C)</p> Signup and view all the answers

    What does a lower dissociation constant (Kd) indicate about an antibody's affinity for an antigen?

    <p>Higher affinity for the antigen. (C)</p> Signup and view all the answers

    Which process is crucial for the activation of T Cell Receptors (TCR)?

    <p>CD3 and ζ chains initiating signaling. (C)</p> Signup and view all the answers

    What role does IL-7 play in T lymphocyte development?

    <p>Maintains and expands the progenitors of T lymphocytes. (D)</p> Signup and view all the answers

    What is the primary consequence of positive selection in T lymphocyte development?

    <p>Ensures T cells can recognize microbial peptides through MHC. (D)</p> Signup and view all the answers

    What is an implication of the cross-reaction phenomenon in antibody interactions?

    <p>Antibodies may bind to other similar antigens produced against one antigen. (B)</p> Signup and view all the answers

    Why do mouse monoclonal antibodies induce immune response when injected into humans?

    <p>They are foreign proteins that the human immune system recognizes. (C)</p> Signup and view all the answers

    What aspect of T cell receptor (TCR) structure is most variable?

    <p>The CDR3 region. (D)</p> Signup and view all the answers

    What is the primary purpose of negative selection in T cell development?

    <p>To eliminate T cells that recognize self peptides too strongly. (C)</p> Signup and view all the answers

    What is the role of Bruton’s tyrosine kinase (Btk) in B cell maturation?

    <p>It signals for survival and proliferation from the pre-BCR. (A)</p> Signup and view all the answers

    How does the pre-BCR complex influence Ig gene rearrangement?

    <p>It shuts off light-chain gene expression. (A)</p> Signup and view all the answers

    Which selection process allows mature B cells to express complete antigen receptors?

    <p>Positive selection (B)</p> Signup and view all the answers

    What occurs as a result of negative selection in immature B cells?

    <p>They re-express VDJ recombinase for receptor editing. (A)</p> Signup and view all the answers

    What is the significance of the double-negative T cell stage in T cell differentiation?

    <p>It is characterized by the rearrangement of TCR beta chain. (C)</p> Signup and view all the answers

    What defines the transition from double-negative to double-positive T cells?

    <p>Expression of the invariant protein pre-Tα. (B)</p> Signup and view all the answers

    What is the consequence of a mutation in Bruton’s tyrosine kinase (Btk) for boys?

    <p>Complete failure of B-cells to develop. (C)</p> Signup and view all the answers

    What occurs during the process of allelic exclusion in B cells?

    <p>Only one inherited allele is used for Ig heavy chain production. (A)</p> Signup and view all the answers

    What are the gene segments present in the antigen receptor gene loci?

    <p>V, D, and C segments (B)</p> Signup and view all the answers

    During Ig heavy-chain expression, what is the order of gene rearrangement?

    <p>D joining to J, followed by V joining to the complex (A)</p> Signup and view all the answers

    Which proteins make up the VDJ recombinase essential for somatic recombination?

    <p>RAG-1 and RAG-2 proteins (B)</p> Signup and view all the answers

    What constitutes the pre-B cell receptor (pre-BCR)?

    <p>Membrane-associated Ig μ protein and surrogate light chains (C)</p> Signup and view all the answers

    What type of lymphocytes express VDJ recombinase?

    <p>Immature B and T lymphocytes (C)</p> Signup and view all the answers

    Which statement is true about the arrangement of Ig light chains and TCR chains?

    <p>They follow the same sequence but lack D segments (C)</p> Signup and view all the answers

    What is the purpose of junctional diversity in antigen receptors?

    <p>To maximize variations in the CDR3 regions (A)</p> Signup and view all the answers

    What happens to the DNA breaks during somatic recombination?

    <p>Ligases repair DNA breaks to produce full-length recombined segments (A)</p> Signup and view all the answers

    Flashcards

    What are the two main regions of a lymphocyte antigen receptor?

    Variable regions (V) are responsible for recognizing antigens, while constant regions (C) are conserved domains that contribute to the function of the receptor.

    What are hypervariable regions (CDRs) and their role in antigen recognition?

    Hypervariable regions (CDRs) are short stretches within the variable region that directly bind to specific epitopes on antigens.

    What are the BCR and TCR complexes?

    The BCR complex in B cells and the TCR complex in T cells both contain plasma membrane antigen receptors and signaling molecules that transmit signals upon antigen recognition.

    What is the main difference in antigen targets between BCR and TCR complexes?

    The B cell receptor (BCR) complex is involved in the recognition of free antigens, while the T cell receptor (TCR) complex recognizes antigens presented by MHC molecules.

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    What are the Fab and Fc fragments of an antibody, and what are their functions?

    The antibody's Fab fragment contains the antigen-binding site and consists of a whole light chain and a portion of the heavy chain, while the Fc fragment is responsible for effector functions such as complement activation and antibody-dependent cell-mediated cytotoxicity.

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    What is the role of the Hinge region in antibodies?

    The Hinge region allows the two Fab regions of an antibody to move independently, increasing its ability to bind to multiple epitopes on the same antigen.

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    What are linear and conformational epitopes, and how do they differ?

    Linear epitopes are recognized as a continuous sequence of amino acids, while conformational epitopes involve a specific 3D structure formed by the protein.

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    What does affinity refer to in the context of antigen-antibody interactions?

    Affinity describes the strength of the interaction between a single antibody binding site and a single epitope.

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    Dissociation Constant (Kd)

    The concentration of an antigen needed to bind to half of the available antibody molecules in a solution.

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    Affinity Maturation

    The increase in the strength of the antigen-binding strength by antibodies over time.

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    Avidity

    The cumulative strength of the binding of all the antigen-binding sites on an antibody.

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    Cross-Reaction

    Antibodies produced against one antigen can also bind to similar, structurally-related antigens.

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    Monoclonal Antibodies

    Monoclonal antibodies are produced by a single clone of B cells and have identical antigen-binding specificity.

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    Positive Selection

    Immature T cells that recognize MHC molecules in the thymus survive and mature.

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    Negative Selection

    T cells that strongly recognize self-peptides bound to self-MHC are eliminated.

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    CD4 and CD8 Coreceptors

    CD4 and CD8 are coreceptors on T cells that recognize nonpolymorphic portions of MHC molecules.

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    Somatic Recombination

    The process of rearranging DNA segments within the antigen receptor gene loci to create a diverse repertoire of antigen receptors.

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    VDJ Recombinase

    A lymphoid-specific enzyme complex responsible for mediating the rearrangement of antigen receptor gene segments during somatic recombination. It is crucial for the generation of diverse antigen receptors.

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    RAG-1 and RAG-2

    The process of bringing two DNA segments close together and cleaving them at specific sites, which is a crucial step in somatic recombination.

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    Combinatorial Diversity

    The diversity generated by the random combination of different V, D, and J gene segments during somatic recombination. This increases the variety of antigen receptors that can be produced.

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    Junctional Diversity

    Further diversification of the antigen receptor by introducing random nucleotide changes at the junctions between the V, D, and J segments during somatic recombination. This further enhances the diversity of antigen receptors.

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    Large Pre-B Cell

    A precursor stage of B cell development where a pre-B cell receptor (pre-BCR) is assembled. This pre-BCR is composed of a membrane-bound IgM heavy chain and surrogate light chain.

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    Small Pre-B Cell

    A stage of B cell development where light chain gene rearrangement is initiated.

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    Mature B Cell

    A fully mature B cell that expresses both IgM and IgD on its surface, allowing it to respond to a wider range of antigens.

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    What is the 'B cell receptor' complex?

    The B cell receptor (BCR) complex, found on mature B-cells, forms during differentiation and includes the pre-B cell Receptor (pre-BCR).

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    What is a 'pre-B cell receptor' and when does it form?

    The pre-BCR complex is present on pre-B cells during their development. It forms by combining heavy 'mu' chains of IgM class, which accumulate in the cytoplasm, with short Ig-α and Ig-β chains.

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    What is Btk and its role in B cell maturation?

    Btk, encoded on the X chromosome, is essential for the pre-BCR to send signals that are important for B-cell survival, proliferation, and maturation. Mutations in Btk lead to the failure of pre-B cell survival and, thus, B cell maturation, causing X-linked agammaglobulinemia (XLA).

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    What is 'allelic exclusion' and its importance in B cell development?

    Allelic exclusion ensures that only one of the two inherited alleles of the Ig heavy chain is actively expressed in each B cell. This is crucial to maintain clonal specificity.

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    How does the pre-BCR influence Ig gene rearrangement?

    Signals from the pre-BCR complex stop the expression of surrogate light chains and activates the κ light-chain locus, making it available for recombination. This helps in producing a complete BCR.

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    What is 'positive selection' in B cell development?

    Mature B cells that express complete antigen receptors undergo positive selection.

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    What is 'negative selection' and how does it prevent autoimmune reactions?

    Immature B cells that bind to self-antigens in bone marrow with high affinity go through a process called 'negative selection.' This could involve receptor editing—changing the specificity of the BCR by generating a different light chain—to prevent harmful immune responses.

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    What happens during the 'double-negative' (DN) stage of T cell development?

    Double-negative (DN) thymocytes, which lack both CD4 and CD8 markers, initially undergo rearrangement of genes coding for the beta chain of the T-cell receptor (TCR). This process leads to the creation of a unique antigen-binding site.

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    Study Notes

    Antigen Recognition in the Adaptive Immune System

    • Lymphocyte antigen receptors recognize diverse antigens and transmit activating signals to cells.
    • B cell and T cell antigen receptors have different recognition properties.
    • Receptor diversity in lymphocytes is generated through various mechanisms.

    Antigen Receptors of Lymphocytes

    • Variable (V) regions of receptors recognize antigens.
    • Constant (C) regions are conserved in receptors.
    • Complementarity-determining regions (CDRs) are short stretches in variable regions that contribute to antigen receptor function.
    • B cell receptors (BCR) complexes and T cell receptors (TCR) complexes contain sets of plasma membrane antigen receptors and signaling molecules.
    • They function in antigen recognition, signal transduction, cell division, differentiation, and effector function.

    Antibodies

    • Antibodies have three hypervariable regions (CDRs) located at the junction of V and C regions. CDR3 has the greatest variability and contributes most to antigen binding.
    • The fragment, antigen-binding (Fab), contains the light chain and the V and first C domains of a heavy chain.
    • The Fc (fragment, crystalline) region is in the constant heavy chain domains and is responsible for the biologic activity and effector function of antibodies.
    • The hinge region links the Fab and Fc regions.
    • Antibodies have different classes (isotypes) of heavy chains (μ, δ, γ, ε, and α) with distinct functions and plasma concentrations.
    • Two types of light chains (κ and λ) are present. κ or λ remains fixed throughout the life of each B cell clone.
    • Light chains do not participate in effector functions, except for binding and neutralizing microbes, and toxins.

    Binding of Antigens to Antibodies

    • Epitopes are parts of antigens recognized by antibodies. Antigens can be linear or conformational.
    • The strength of interaction is called affinity and is determined by dissociation constant (Kd). The lower the Kd, the higher the affinity.
    • Affinity maturation is an increase in antigen-binding strength during an immune response.
    • Antibodies against one antigen can cross-react with other structurally similar antigens.

    Generation of Hybridomas and Monoclonal Antibodies

    • Monoclonal antibodies are used in therapeutics and diagnostics.
    • Mouse monoclonal antibodies induce human immune responses.
    • Recombinant DNA technology generates monoclonal antibodies of desired specificity using gene technology.

    T Cell Receptors for Antigens

    • T cell receptors have variable regions (CDRs) that enable antigen recognition. CDR3 has the largest variability.
    • TCRs interact with both the MHC molecule and the peptide presented.
    • TCR activation requires CD3 and ζ chains, and CD4 or CD8 coreceptors.

    Features of Antigen Recognition

    • Immunoglobulins (Igs) have three CDRs in VH and three CDRs in VL. Heavy chain class switching changes the function and secretion of Igs. Igs have low Kd.
    • T cell receptors (TCRs) also have three CDRs in Va and three CDRs in Vb. TCRs have high Kd.

    Development of T and B Lymphocytes

    • Lymphocytes with distinct specificities develop before antigen encounter.
    • Growth factors and stroma cells promote survival and proliferation in bone marrow and thymus.
    • Positive selection ensures that cells survive if they can partially recognize MHC molecules.
    • Negative selection eliminates cells with high affinity for self-peptides that are presented by self MHC.

    Production of Diverse Antigen Receptors

    • Hematopoietic stem cells contain Ig and TCR genes.
    • Receptor gene loci contain V, J, and C gene segments (V, D, J).
    • Variable regions are highly variable. One or a few constant regions are present.

    Somatic Recombination and Expression of Immunoglobulin

    • Ig heavy chain expression involves D-J joining followed by V-DJ joining.
    • Recombined genes are transcribed to give rise to precursor mRNA and translated to create protein chains.
    • Recombination of light chains and T cell receptors follows similar mechanisms. D regions are not part of light chain recombination.
    • V gene recombines directly with a J gene segment.

    Diversity in Antigen Receptors

    • Somatic recombination is mediated by V (D) J recombinase.
    • Recombination activating genes (RAG)1 and RAG2 proteins bring together gene segments.
    • Combinatorial diversity and junctional diversity increase the total potential diversity of receptors.
    • DNA breaks are repaired to generate complete recombinations.

    Maturation and Selection of B Lymphocytes

    • Large pre-B cells survive and proliferate if their heavy chain genes rearrange properly and a pre-BCR assembles.
    • Small pre-B cells engage in light-chain rearrangements.
    • Immature B cells assemble complete membrane IgM receptors.
    • Mature B cells simultaneously express IgD.

    B-Cell Differentiation

    • Heavy μ chains of IgM accumulate in cytoplasm and combine with short Ig-a and Ig-β chains to form pre-B cell receptors.
    • Pre-BCR signaling allows for the expression of the light chains and for functional IgM to be produced.
    • Subsequent differentiation occurs as the B cells encounter antigens.

    Role of the Pre-BCR Complex

    • Pre-BCR activation involves Bruton's tyrosine kinase (Btk), a protein encoded on the X chromosome.
    • Btk activation delivers signals from the pre-BCR and mediates B cell survival, proliferation, and maturation.
    • Mutations in Btk cause X-linked agammaglobulinemia (XLA), a disease resulting from the failure of pre-B cells to survive and develop into mature B cells.
    • Allelic exclusion ensures that each B cell expresses only one heavy-chain gene.

    Mature B-Cells

    • Positive selection results in the expression of complete antigen receptors.
    • Negative selection assures that mature B cells that bind self-antigens are eliminated.

    Maturation and Selection of MHC-Restricted T Lymphocytes

    • Pro-T cells are double-negative cells that increase in number through thymic IL-7 influence.
    • TCR beta chain is first expressed at the double-negative pre-T cell stage and is mediated by VDJ recombinase.
    • TCR beta is then expressed with a pre-T protein in association with an invariant protein (pre-Ta).
    • Double-positive cells mature and develop to single-positive CD4+ or CD8+ T-cell.
    • Cells that do not express antigen receptors die through apoptosis.

    T-Cell Differentiation: Double-Negative (DN) Stage

    • Thymocytes rearrange genes coding for the beta chain of the T-cell receptor.
    • Gene segments are selected and joined to produce a unique antigen-binding site.

    T-Cell Differentiation: Double-Negative (DN) Stage

    • Alpha and beta chains recognize antigen.
    • Six other chains (in three pairs) assist with intracellular signaling.

    Positive and Negative Selection of Thymocytes

    • Positive selection creates cells that recognize self-MHC.
    • Negative selection eliminates cells that bind self-antigens too strongly.

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    Antigen Recognition in Adaptive Immune System PDF

    Description

    Explore the intricacies of antigen recognition in the adaptive immune system, focusing on lymphocyte antigen receptors. Learn the differences between B cell and T cell receptors, and understand the mechanisms behind receptor diversity and antibody structure.

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