Immunogenicity and Anti-Drug Antibodies
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Immunogenicity and Anti-Drug Antibodies

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What is the definition of immunogenicity?

  • The immune response generated by the host against a therapeutic protein (correct)
  • The effectiveness of a therapeutic protein in treating diseases
  • The level of toxicity in therapeutic proteins
  • The ability of a therapeutic protein to bind to its target

    • Which section of the FDA-approved label contains information about immunogenicity?

  • Section 3.1: Drug Interactions
  • Section 5.4: Clinical Pharmacology
  • Section 6.2: Adverse Reactions (correct)
  • Section 6.2: Immunogenicity

    • What is a characteristic of binding anti-drug antibodies (ADA)?

  • They can affect the pharmacokinetics of the drug. (correct)
  • They are responsible for a complete loss of drug efficacy.
  • They exclusively enhance the drug's effectiveness.
  • They block the drug's interaction with the target.

    • What is one of the consequences of neutralizing anti-drug antibodies?

    <p>Loss of efficacy of the drug</p> Signup and view all the answers

    Why is the study of immunogenicity important in biotherapeutics?

    <p>It helps predict adverse reactions and efficacy related to the immune response.</p> Signup and view all the answers

    What are immune-privileged sites primarily designed to protect?

    <p>Specific organs from immune responses</p> Signup and view all the answers

    Why is immune privilege in the testis crucial for male fertility?

    <p>It limits inflammation that could harm fertility</p> Signup and view all the answers

    How does the mother typically tolerate the presence of fetal antigens during pregnancy?

    <p>Through immunosuppression mechanisms</p> Signup and view all the answers

    What role do self antigens play in the context of immune privilege in the testis?

    <p>They are expressed after the immune system is developed</p> Signup and view all the answers

    Which of the following factors contributes to immune privilege in the placenta?

    <p>Presence of specialized barriers and immunosuppression</p> Signup and view all the answers

    What are examples of 'clearing' ADA based on their effects?

    <p>Both binding and neutralizing ADA</p> Signup and view all the answers

    What is indicated by the development of ADA in terms of plasma drug concentration?

    <p>A rapid decrease in plasma drug concentration</p> Signup and view all the answers

    How are non-clearing ADA commonly described?

    <p>As sustaining ADA</p> Signup and view all the answers

    Which type of T cells promote ADA generation?

    <p>Thelper cells</p> Signup and view all the answers

    What is considered a driver of immunogenic response in T cells?

    <p>Context of presentation to T cells</p> Signup and view all the answers

    What is the role of Treg cells in relation to ADA?

    <p>They limit ADA generation</p> Signup and view all the answers

    What are T cell epitopes and Tregitopes related to?

    <p>Immunogenic response</p> Signup and view all the answers

    What is a typical expectation concerning plasma drug concentrations with multiple dosing?

    <p>Decreased plasma concentrations</p> Signup and view all the answers

    What role do dendritic cells (DCs) play in the lamina propria?

    <p>Take up and process protein antigens from microbes.</p> Signup and view all the answers

    Which cytokines are important for the differentiation of bacterial antigen-specific Th17 cells?

    <p>IL-6 and IL-23</p> Signup and view all the answers

    What promotes the differentiation of bacterial antigen-specific regulatory T cells (Tregs)?

    <p>TGF-β and retinoic acid</p> Signup and view all the answers

    How do keratinocytes contribute to the immune response in the epidermis?

    <p>They produce antimicrobial peptides and various cytokines.</p> Signup and view all the answers

    Where do the skin-homing properties of effector lymphocytes develop?

    <p>In skin-draining lymph nodes</p> Signup and view all the answers

    Which signaling factors are involved in the migration of effector T cells into the skin?

    <p>Homing molecules such as CCR4, CCR8, and CCR10</p> Signup and view all the answers

    What is the primary function of the epidermis in relation to microbes?

    <p>Provide a physical barrier to microbial invasion.</p> Signup and view all the answers

    What initiates the expression of CCR10 in the skin?

    <p>Ultraviolet rays in sunlight (UVB)</p> Signup and view all the answers

    What is the role of intestinal epithelial cells in the gastrointestinal immune system?

    <p>They are involved in responses to pathogens and antigen sampling.</p> Signup and view all the answers

    Where are M cells primarily located within the gut?

    <p>In the regions overlying Peyer’s patches.</p> Signup and view all the answers

    What distinguishes M cells from absorptive epithelial cells?

    <p>M cells exhibit large fenestrations in their membranes.</p> Signup and view all the answers

    What characteristic role do the lymphocytes play following their differentiation in lymphoid tissues?

    <p>They acquire gut-homing properties.</p> Signup and view all the answers

    What type of tissues induce dendritic cells in the gut?

    <p>Gut-associated lymphoid tissues (GALT).</p> Signup and view all the answers

    What is the primary composition of the gastrointestinal system's structure?

    <p>A tube-like structure lined by epithelial cells.</p> Signup and view all the answers

    Which of the following statements about M cells is true?

    <p>M cells are fewer in number compared to absorptive epithelial cells.</p> Signup and view all the answers

    What function does the lamina propria serve in relation to the epithelial layer?

    <p>It contains blood and lymphatic vessels.</p> Signup and view all the answers

    Study Notes

    Immunogenicity

    • Immunogenicity is the host immune response against a therapeutic protein
    • Typically, immunogenicity is studied in the context of anti-drug antibody (ADA) formation
    • All FDA-approved biotherapeutics include a section on immunogenicity in their label (section 6.2) under Adverse Reactions

    Anti-Drug Antibodies

    • There are two main classes of ADAs: binding and neutralizing
    • Binding ADAs interact with the drug molecule but do not inhibit its binding to the pharmacologic target
      • Binding ADAs may impact pharmacokinetics and safety

    Neutralizing ADAs

    • Neutralizing ADAs directly block the interaction of a drug with its pharmacologic target
      • Neutralizing ADAs result in loss of efficacy, impact pharmacokinetics, and may impact safety

    'Clearing' ADAs

    • Both binding and neutralizing ADAs can be categorized as 'clearing'
    • 'Clearing' ADAs are detected based on their effects on pharmacokinetics
    • Non-clearing ADAs are also referred to as 'sustaining' ADAs
      • A typical expectation is a rapid decrease in plasma drug concentrations upon ADA development
      • Decreased plasma concentrations following multiple dosing (typical expectation is accumulation)

    Physiologic Drivers of Immunogenicity

    • Immunogenicity is largely thought to be a T-cell dependent phenomenon
      • The context of presentation to T cells is likely a driver of the ultimate response
      • Presentation to T helper cells leads to ADA generation
      • Presentation to Treg cells limits ADA generation

    The Gastrointestinal Immune System

    • Intestinal epithelial cells lining the small and large bowel are part of the gastrointestinal innate immune system involved in responses to pathogens and antigen sampling
      • The gastrointestinal system is a tube-like structure lined by a continuous epithelial cell layer that serves as a physical barrier
      • The lamina propria underlies the epithelium, containing blood vessels, lymphatic vessels, and MALTs

    M Cells

    • M cells are located in regions of the gut epithelium called follicle-associated (or dome) epithelium
    • Antigen may be delivered from the lumen to the GALT through specialized cells called M cells
    • M cells have a thin glycocalyx, short irregular microvilli, and large fenestrations in their membranes, enhancing antigen uptake from the gut lumen

    Homing Properties of Intestinal Lymphocytes

    • The gut-homing properties of effector lymphocytes are imprinted in lymphoid tissues
      • DCs in GALT are induced by cytokines
      • DCs in the lamina propria take up and process protein antigens from microbes and transport them to mesenteric lymph nodes

    Effector and Regulatory T Cells in the Intestinal Mucosa

    • Different subsets of effector CD4+ T cells in the gastrointestinal tract are induced by and protect against different microbial species
    • Th17 effector T cells and regulatory T cells are abundant in the intestinal mucosa
      • Bacterial antigen-specific Th17 cells differentiate from naive CD4+ T cells in GALT in response to antigens presented by DCs
      • Differentiation of bacterial antigen-specific regulatory T cells is promoted by TGF-β and retinoic acid
      • Thymic Tregs that migrate to the intestine expand under the influence of bacterial metabolites

    The Cutaneous Immune System

    • The epidermis provides a physical barrier to microbial invasion
      • The epidermis is made up of keratinocytes
    • Keratinocytes actively respond to pathogens by producing antimicrobial peptides and cytokines

    Homing Properties of Cutaneous Lymphocytes

    • The skin-homing properties of effector lymphocytes are imprinted in skin-draining lymph nodes
    • Ultraviolet rays in sunlight stimulate vitamin D production
    • IL-12 induces the expression of E-selectin ligand CLA, and other signals induce CCR4, CCR8, and CCR10 expression

    Immune-Privileged Tissues

    • Immune responses and associated inflammation in certain parts of the body, including brain, eye, testes, placenta, and fetus, carry a high risk for lethal organ dysfunction
    • These tissues are called immune-privileged sites

    Immune Privilege in the Testis

    • Immune privilege in the testes limits inflammation that may impair male fertility
      • Many self-antigens in the testes are first expressed at puberty, so it is unlikely lymphocytes specific for these antigens are deleted during development
    • Immune privilege in the testes may also prevent autoimmunity

    Immune Privilege and the Fetus

    • The fetus expresses paternally inherited genes that are foreign to the mother
    • The mother is exposed to fetal antigens during pregnancy, and maternal antibodies against paternal MHC molecules are detectable
      • Different molecular and barrier features of the placenta contribute to immune privilege in the fetus

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    Immunogenicity Review Exam 3 PDF

    Description

    This quiz explores the concepts of immunogenicity, focusing on the immune responses to therapeutic proteins. It covers the different classes of anti-drug antibodies, including binding and neutralizing antibodies, as well as their implications on pharmacokinetics and drug efficacy. Understanding these mechanisms is crucial for evaluating the safety and effectiveness of biotherapeutics.

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