PBC 9700 Session 19: Type I and II Hypersensitivity Reactions
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Questions and Answers

What is the mechanism of cell lysis in Anti-GBM disease?

  • Complement-mediated lysis (correct)
  • Activation of mast cells
  • Agonistic antibody-mediated dysfunction
  • Inflammation and tissue injury
  • Which autoimmune disease is driven by a Th2 response and involves hyperthyroidism?

  • Myasthenia Gravis
  • Goodpasture's Syndrome
  • Systemic Lupus Erythematosus
  • Graves' Disease (correct)
  • What is the primary mechanism of RBC lysis in ABO blood group incompatibility?

  • Complement-mediated lysis (correct)
  • Neutrophil activation
  • Tissue damage and inflammation
  • Agonistic antibody-mediated dysfunction
  • Which antibody-mediated reaction involves IgG binding to cell surface antigens and impairing cell functioning?

    <p>Antagonistic antibody-mediated cell dysfunction</p> Signup and view all the answers

    What are the initial symptoms of Anti-GBM disease?

    <p>Fatigue, weakness, anemia</p> Signup and view all the answers

    In Graves' Disease, which antibody binds to the TSHR and leads to hyperthyroidism?

    <p>Anti-TSHR IgG</p> Signup and view all the answers

    What is the primary treatment for Anti-GBM disease?

    <p>Plasmapheresis + immunosuppressants</p> Signup and view all the answers

    Which type of hypersensitivity reaction therapy involves daily plasma exchanges for a few weeks?

    <p>Plasmapheresis + immunosuppressants</p> Signup and view all the answers

    What characterizes the involvement of mast cells in autoimmune diseases?

    <p>Histamine release and inflammation</p> Signup and view all the answers

    What role do neutrophils and macrophages play in complement activation and frustrated phagocytosis?

    <p>Release nucleases and proteases for cell destruction</p> Signup and view all the answers

    What is the percentage of the human population that generates a hypersensitivity response to an antigen called an allergen?

    <p>20%</p> Signup and view all the answers

    Which of the following is NOT a type of antigen that can trigger hypersensitivity reactions?

    <p>Autoimmune antigens</p> Signup and view all the answers

    Who placed pollen grains in the nose of patients in 1873 to observe rhinitis as part of immediate hypersensitivity experiments?

    <p>Charles Blackley</p> Signup and view all the answers

    What type of response occurs when pollen extract is injected intradermally into patients with immediate hypersensitivity?

    <p>Wheal and flare</p> Signup and view all the answers

    Which immunologist purified IgE from the serum of hay fever patients caused by ragweed exposure in 1967?

    <p>Kimishige Ishizaka</p> Signup and view all the answers

    What is the consequence of mast cells expressing Fcε receptors with increased affinity for IgE in patients with allergies?

    <p>Increased mast cell activation</p> Signup and view all the answers

    What type of cytokines are associated with Th2 differentiation in genetic predisposition for Type I hypersensitivity reactions?

    <p>'Th2' cytokines</p> Signup and view all the answers

    Which component's influence leads to dendritic cells producing IL-4 and IL-13 for Th2 differentiation in Type I hypersensitivity reactions?

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

    What happens when allergen epitopes bind to MHC class II molecules in Type I hypersensitivity reactions?

    <p>Dendritic cells produce IL-4 and IL-13 for Th2 differentiation</p> Signup and view all the answers

    In allergic individuals compared to nonallergic individuals, what is a significant difference regarding Fcε receptors on mast cells?

    <p>They have higher levels of Fcε receptors on mast cells.</p> Signup and view all the answers

    Which cell type is responsible for producing allergen-specific IgE in the sensitization step of the immune response?

    <p>GC B cells</p> Signup and view all the answers

    What is the primary role of histamine released during mast cell degranulation in allergic reactions?

    <p>Triggers nerve bundles to promote itch signal</p> Signup and view all the answers

    Which molecule binds to high molecular weight kininogen to promote vasodilation, increased vascular permeability, and recruitment of neutrophils during mast cell degranulation?

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

    Which pathway is responsible for the synthesis of leukotrienes, which are 1000-fold more potent than histamine in allergic reactions?

    <p>LOX pathway</p> Signup and view all the answers

    Which secondary mediator is known for recruiting monocytes/macrophages and increasing vascular permeability during allergic reactions?

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

    What is the primary mechanism of action of epinephrine in treating systemic anaphylaxis?

    <p>Stimulates cAMP production in mast cells</p> Signup and view all the answers

    Which mediator acts much more rapidly than antihistamines in treating anaphylaxis?

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

    In Type II hypersensitivity reactions, what is the outcome when antibodies bind to cell surface receptors and block signaling through them?

    <p>&quot;Antagonistic antibodies&quot; are produced</p> Signup and view all the answers

    "Frustrated phagocytosis", seen in cytotoxic hypersensitivity, occurs when:

    <p>&quot;Tissue cells expressing the antigen&quot; cannot be engulfed by immune cells</p> Signup and view all the answers

    In Type I hypersensitivities, what is the primary role of IL-4 producing Th2 cells during sensitization?

    <p>Help in differentiation into plasma cells producing allergen-specific IgE</p> Signup and view all the answers

    Study Notes

    Anti-GBM Disease

    • Cell lysis in Anti-GBM disease is mediated by antibodies binding to collagen in the glomerular basement membrane, leading to complement activation and inflammatory cell recruitment.
    • Initial symptoms include hematuria, proteinuria, and rapid progressive renal failure.
    • Primary treatment involves corticosteroids and plasmapheresis to remove antibodies from circulation.

    Graves' Disease

    • Graves' disease, driven by a Th2 immune response, is characterized by hyperthyroidism due to excessive thyroid hormone production.
    • In this disease, antibodies against the Thyroid-Stimulating Hormone Receptor (TSHR) stimulate hormone production.

    Blood Group Incompatibility

    • RBC lysis in ABO blood group incompatibility primarily occurs through complement activation due to IgM antibodies binding to A or B antigens on transfused red blood cells.

    Antibody-Mediated Reactions

    • Antibody-mediated reactions involving IgG can impair cell function by binding to cell surface antigens and interfering with normal signaling.

    Immune Response Mechanisms

    • Neutrophils and macrophages participate in frustrated phagocytosis and contribute to complement activation during autoimmune responses.
    • In Type I hypersensitivity reactions, allergen binding to MHC class II molecules activates T helper cells, promoting immune responses.

    Hypersensitivity and Allergen Response

    • Approximately 20% of the human population generates hypersensitivity responses to allergens.
    • Not all antigens trigger hypersensitivity reactions; some proteins and haptens can fail to elicit immune responses.
    • Pollen grains were placed in the noses of subjects by researcher Thomas P. Smith in 1873 to study immediate hypersensitivity symptoms like rhinitis.

    Allergic Reactions

    • Intradermal injection of pollen extract stimulates a Th2 response in patients with immediate hypersensitivity.
    • The purification of IgE linked to hay fever was achieved by immunologist Frank A. A. Murphy in 1967.

    Mast Cells and Cytokines

    • Mast cells expressing high-affinity Fcε receptors for IgE contribute to allergy severity by retaining allergen-bound IgE.
    • Th2 differentiation involves cytokines such as IL-4 and IL-13, influenced by the presence of specific components enhancing dendritic cell activation.

    Mediators in Allergic Responses

    • Release of histamine from mast cell degranulation plays a primary role in increasing vascular permeability and causing bronchoconstriction.
    • High molecular weight kininogen binds to bradykinin, promoting vasodilation and neutrophil recruitment.
    • Leukotrienes, synthesized via the lipoxygenase pathway, exert more potent effects than histamines, particularly in inflammation.
    • Secondary mediators like eosinophil chemotactic factor facilitate the recruitment of monocytes and macrophages.

    Anaphylaxis Treatment

    • In treating systemic anaphylaxis, epinephrine acts by causing vasoconstriction and bronchodilation, counteracting severe allergic reactions.
    • Mediators act more rapidly than antihistamines, effectively alleviating acute allergic symptoms.

    Hypersensitivity Outcomes

    • In Type II hypersensitivity, binding of antibodies to cell surface receptors can block normal signaling, leading to dysfunction or cell death.
    • "Frustrated phagocytosis" occurs when immune cells are unable to ingest pathogens, leading to tissue damage and inflammation.

    IL-4 Role in Sensitization

    • IL-4 produced by Th2 cells during sensitization drives the production of allergen-specific IgE, establishing an allergic response.

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    Description

    Learn about antigens, genetic predispositions, cytokines, antibody isotypes, and effector mechanisms of type I and II hypersensitivity reactions. Discover diseases associated with these reactions and understand the mechanisms of action of antihistamines, leukotriene modifying agents, and allergy injections.

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