Antibody Antigenic Determinants

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Questions and Answers

How would the introduction of a novel synthetic epitope, designed to mimic a conformational B-cell epitope on a viral capsid, impact an ongoing humoral immune response in a vaccinated individual?

  • It would have no impact on the existing humoral immune response, as established antibody specificities are immutable.
  • It would solely enhance T-cell mediated cytotoxicity, leading to the destruction of infected cells displaying the conformational epitope.
  • It could potentially induce a shift in the antibody response, possibly altering the original focus by directing it towards the synthetic epitope. (correct)
  • It would likely lead to a narrowed antibody repertoire, focusing the immune response exclusively on the synthetic epitope.

In the context of immune complex-mediated type III hypersensitivity, which statement accurately describes the mechanism of tissue damage induced after the formation of soluble immune complexes?

  • The immune complexes trigger mast cell degranulation, leading to the release of histamine and leukotrienes that cause vasodilation and increased vascular permeability.
  • The immune complexes deposit in tissues and activate the complement system, leading to neutrophil recruitment and release of destructive enzymes causing localized damage. (correct)
  • The immune complexes cross-link with IgE antibodies on basophils, resulting in the systemic release of cytokines and anaphylactic shock.
  • The immune complexes directly lyse host cells through the activation of perforin and granzyme pathways.

If a patient with a history of recurrent bacterial infections is found to have a genetic defect that impairs the expression of certain MHC class II alleles, how would this most directly affect the immune response to T-dependent antigens?

  • It enhances the presentation of endogenous antigens to CD8+ cytotoxic T cells, leading to increased cell-mediated cytotoxicity.
  • It diminishes the presentation of processed antigens to CD4+ T helper cells, reducing T cell help for B cell activation and antibody production. (correct)
  • It blocks the interaction between T cell receptors and superantigens, causing a general suppression of T cell activation.
  • It impairs the activation of B cells, preventing isotype switching and affinity maturation.

A researcher is studying the development of novel vaccines targeting highly variable viral pathogens. Which strategy would best focus the immune response on conserved viral epitopes, minimizing the impact of antigenic variation?

<p>Engineering the vaccine to deliver conserved epitopes in a manner that preferentially stimulates T-cell responses over B-cell responses. (D)</p> Signup and view all the answers

In the context of antibody production, what is the most critical difference between isotypic, allotypic, and idiotypic determinants that dictates the immune response?

<p>Isotypic determinants define antibody class and function, allotypic determinants reflect individual genetic variation, while idiotypic determinants specify antigen-binding specificity. (A)</p> Signup and view all the answers

Considering the role of adjuvants in vaccine design, how does Freund's Complete Adjuvant (FCA) enhance the immune response, especially concerning B-cell epitopes?

<p>FCA creates a depot effect for the antigen, allowing for sustained stimulation of B cells and enhanced antibody production. (C)</p> Signup and view all the answers

How does the three-dimensional structure of an antigen primarily affect its recognition by B cells compared to T cells?

<p>B cells recognize conformational epitopes, while T cells recognize linear peptide fragments presented on MHC molecules. (B)</p> Signup and view all the answers

Which of the following best describes the implications of soluble immune complex formation in the pathogenesis of type III hypersensitivity reactions?

<p>Soluble immune complexes activate complement, attracting neutrophils that release enzymes and cause localized tissue damage. (B)</p> Signup and view all the answers

What is the functional consequence of injecting an antibody with minimal variation in its isotypes and allotypes into an animal, to then produce an anti-idiotypic antibody?

<p>It will specifically target and bind to the unique antigen-binding site of the injected antibody, potentially modulating the immune response. (C)</p> Signup and view all the answers

If a novel therapeutic antibody is designed to target a conformational epitope on a tumor cell, how might heat-induced denaturation of the tumor cells affect the antibody's efficacy?

<p>Denaturation would likely reduce or eliminate antibody binding by disrupting the three-dimensional structure of the epitope, decreasing efficacy. (C)</p> Signup and view all the answers

Flashcards

Antigen

Organism or molecule part recognized by the immune system, mainly B and T cells.

Epitope

Smallest part of an antigen recognized by lymphocytes.

Antibodies as Immunogens

Glycoproteins that can induce an antibody response.

Isotypic Determinants

Constant region determinants defining heavy chain class/subclass. Unique across heavy chains, similar across light chains.

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Allotypic Determinants

Subtle amino acid differences encoded by different alleles of isotypic genes. Detected by comparing antibody classes among different individuals.

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Idiotypic Determinants

Unique antigen-binding sites (variable regions) of an antibody, formed by specific amino acid sequences.

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Epitope (Antigenic Determinant)

Specific part of an antigen bound by immune components.

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Conformational Epitope

3D structures on an antigen surface recognized by B cell receptors or antibodies.

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Linear Epitope

Sequence of amino acids in a linear chain recognized by T cells.

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Adjuvant

Substance administered with an antigen to enhance the immune response.

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Study Notes

  • An antigen is recognized by the immune system (B and T cell lymphocytes).
  • The smallest part of an antigen that is recognized by lymphocytes is called an antigenic determinant or epitope.
  • Antibodies are glycoproteins that can act as immunogens to induce an antibody response.
  • Anti-IG antibodies are useful for studying immune responses.

Types of Antigenic Determinants on Antibodies

  • Isotypic
  • Allotypic
  • Idiotypic

Isotypic Determinants

  • Located on the constant region of antibodies.
  • Define each heavy chain class and subclass.
  • Unique across constant heavy chains.
  • Similar across light chains.

Allotypic Determinants

  • Subtle amino acid differences encoded by different alleles of isotypic genes.
  • Detected by comparing the same antibody class among different strains.
  • Can occur on both light and heavy chains.

Idiotytpic Determinants

  • Generated by the confirmation of the amino acid sequences of the heavy and light chain variable regions specific for each antigen
  • Anti-idiotypic antibodies are produced by injecting antibodies with minimal variation in their isotypes and allotypes to recognize idiotypic differences.

Role of an Epitope in Immune Activation

  • An epitope is the specific part of an antigen that is recognized and bound by the immune system.
  • Also called an antigenic determinant.

Recognition by B Cells

  • B cell receptors (BCRs) or antibodies recognize conformational epitopes (3D structures) on the surface of an antigen.
  • Binding triggers B cell activation, leading to clonal expansion and antibody production.

Recognition by T Cells

  • T cells recognize linear epitopes, which are peptide fragments of the antigen.
  • The epitope is presented on MHC molecules by antigen-presenting cells (APCs).
  • Interaction between the TCR and the epitope-MHC complex activates T cells.

Immune Activation

  • Epitope binding initiates an adaptive immune response, leading to:
    • B cell activation and antibody production
    • T cell activation and the recruitment of other immune cells

Types of Epitopes

  • Linear Epitope: Recognized as a sequence of amino acids in a linear chain (e.g., by T cells).
  • Conformational Epitope: Formed by the 3D structure of an antigen (e.g., recognized by B cells and antibodies).

Immune Complexes

  • The degree to which immune complexes are soluble or insoluble is based on agglutination.
  • Differences are determined by the cross-linking of antigen-bearing particles by antibodies.
  • Cross-linking of antigen-bearing particles by antibodies forms clumps.

Soluble Immune Complexes

  • Antibodies bind to red blood cells without immediate cross-linking.

Insoluble Immune Complexes

  • Anti-antibody molecules target antigenic determinants and form a cross-linked immune complex.
  • Clumping of the immune complex leads to agglutination and insolubility.

Type Three Hypersensitivity

  • Immune complexes (antibodies bound to antigens) float freely in the blood (soluble immune complexes).
  • Antigens can be either external (foreign) or internal (self).
  • IgM or IgG antibodies bind to the antigens to form complexes of various sizes.
  • Macrophages usually remove these immune complexes from the blood, but smaller complexes may remain in circulation.
  • Circulating immune complexes deposit on blood vessel walls, especially in small vessels.
  • Immune complex formation initiates the complement system and activates immune cells.
  • Neutrophils are attracted by activated chemotactic complement proteins and bind to the Fc portion of antibodies in the immune complex, releasing destructive substances that cause cell damage.
  • Damage to endothelial cells and the basement membrane of blood vessels increases permeability, leading to leakage into surrounding tissue, provoking inflammation and tissue damage.

B-Cell Epitopes vs. T-Cell Epitopes

  • Both B-cell and T-cell epitopes can consist of linear sequences of amino acid residues.
  • B-cell epitopes are generally located on the surface of a protein antigen.
  • T-cell epitopes are generally located in the interior of a protein antigen.

Immunogenicity

  • B-cell epitopes may lose their immunogenicity when a protein antigen is denatured by heat.
  • Immunodominant epitopes are determined in part by the MHC molecules expressed by an individual.
  • Both B-cell and T-cell epitopes generally arise from proteins.
  • Multiple different epitopes may occur in the same antigen.
  • The immunogenicity of B-cell epitopes may depend on the three-dimensional structure of the antigen.
  • The immune response to B-cell epitopes may be enhanced by coadministration of Freund’s complete adjuvant.

Adjuvants

  • An adjuvant is a substance administered alongside an antigen to enhance the immune response.
  • Freund's Complete Adjuvant (FCA) contains inactivated mycobacteria and oil.
  • FCA helps stimulate a stronger and more prolonged immune response.
  • FCA primarily enhances B-cell responses by promoting stronger activation and differentiation of B cells, leading to more effective antibody production.

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