12.2 Immunomodulation
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Questions and Answers

What is the primary action of rapamycin in the context of selective immunosuppression?

  • Inhibits mTOR (correct)
  • Enhances cytokine production
  • Stimulates cell proliferation
  • Activates immune cell metabolism

    • Which of the following JAK inhibitors primarily targets JAK1 and is used to treat atopic dermatitis?

  • Ruxolitinib
  • Baricitinib
  • Oclacitinib (correct)
  • Tofacitinib

    • Which of the following is NOT considered a benefit of the BCG vaccine?

  • Leads to reduced macrophage activity (correct)
  • Induces pro-inflammatory cytokine production
  • Enhances cytokine synthesis
  • Increases TLR stimulation

    • Which group of substances is known to activate macrophages in the immune system?

    <p>Bacterial products and complex carbohydrates (C)</p> Signup and view all the answers

    Which cytokines are dependent on JAK1 for their signaling pathway?

    <p>IL-2, IL-4, IL-6, IL-13, IL-31 (C)</p> Signup and view all the answers

    What is the primary function of immunomodulation?

    <p>To alter the immune response (C)</p> Signup and view all the answers

    Which of the following is an example of non-specific immunosuppression?

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

    What is the main mechanism of action for alkylating agents in immunosuppression?

    <p>Prevent cell division by cross-linking DNA (A)</p> Signup and view all the answers

    What type of immunosuppression does the drug cyclosporine provide?

    <p>Selective immunosuppression (C)</p> Signup and view all the answers

    Which of the following describes the action of corticosteroids?

    <p>Inhibits NF-κB activation (D)</p> Signup and view all the answers

    Which of these agents is classified as a DNA synthesis inhibitor?

    <p>Azathioprine (A)</p> Signup and view all the answers

    What role do calcineurin inhibitors like tacrolimus and cyclosporine play in immune response modulation?

    <p>They inhibit IL-2 synthesis (B)</p> Signup and view all the answers

    Which immunomodulatory agent works by blocking cytokine synthesis and T cell responses?

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

    What is the primary role of mTOR in cellular processes?

    <p>Regulates cell metabolism, growth, proliferation, and survival (C)</p> Signup and view all the answers

    Which of the following is a treatment for atopic dermatitis that mainly inhibits JAK1?

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

    Which bacterial product is known to enhance pro-inflammatory cytokine production?

    <p>Bacille Calmette-Guerin (BCG) (A)</p> Signup and view all the answers

    Which vitamins are noted for their role in the stimulation of the immune system?

    <p>Vitamins A, D, and E (D)</p> Signup and view all the answers

    What type of signaling does JAK-STAT primarily influence?

    <p>Cell division, cell death, and immune response (C)</p> Signup and view all the answers

    What is the main purpose of immunomodulation?

    <p>To either enhance or suppress the immune response (D)</p> Signup and view all the answers

    Which of the following agents is classified as a non-specific immunosuppressant?

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

    What mechanism do alkylating agents like Cyclophosphamide utilize in immunosuppression?

    <p>Cross-linking DNA to prevent cell division (C)</p> Signup and view all the answers

    Selective immunosuppression through calcineurin inhibitors primarily inhibits the synthesis of which interleukin?

    <p>IL-2 (A)</p> Signup and view all the answers

    What effect do corticosteroids have on the immune system?

    <p>They block cytokine synthesis and dampen T cell responses. (A)</p> Signup and view all the answers

    What characterizes selective immunosuppression?

    <p>It specifically targets and inhibits certain immune functions. (C)</p> Signup and view all the answers

    Which drug is a cytotoxic agent that blocks the production of tetrahydrofolate?

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

    What is the primary action of radiation in the context of non-specific immunosuppression?

    <p>It prevents cell division through DNA damage. (D)</p> Signup and view all the answers

    Flashcards

    Immunomodulation

    The use of agents to either boost or suppress the immune response.

    Immunosuppression

    A type of immunomodulation that aims to reduce or dampen the immune response.

    Non-specific Immunosuppression

    Immunosuppression that affects all parts of the immune system, regardless of the specific target.

    Selective Immunosuppression

    Immunosuppression that targets specific parts of the immune system, like certain cells or processes.

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    Immunopotentiation

    A type of immunomodulation that amplifies or strengthens the immune response.

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    Radiation

    A non-specific immunosuppressant that prevents cell division by damaging DNA.

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    Corticosteroids

    A non-specific immunosuppressant that blocks the synthesis of cytokines and T cell responses.

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    Calcineurin Inhibitors

    A group of immunosuppressants that act by inhibiting the synthesis of IL-2, a key immune signaling molecule.

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    What is the mechanism of action for Rapamycin?

    Rapamycin forms a complex with an immunophilin, blocking the mTOR protein, which is a critical regulator of cell growth, metabolism, survival, and proliferation.

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    What is the target of JAK Inhibitors?

    JAK inhibitors, like Oclacitinib, target and suppress the JAK-STAT signaling pathway, which is essential for immunity, cell division, and cell death.

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    What is the primary target of Oclacitinib?

    Oclacitinib, a JAK inhibitor, primarily inhibits JAK1, a key kinase involved in the production of cytokines like IL-2, IL-4, IL-6, IL-13, and IL-31.

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    How do bacterial products stimulate the immune system?

    Bacterial products, such as BCG (Bacille Calmette-Guerin), stimulate the immune system by acting as PAMPs (Pathogen-Associated Molecular Patterns) and triggering TLRs (Toll-Like Receptors), leading to the production of cytokines.

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    How do complex carbohydrates stimulate the immune system?

    Complex carbohydrates like zymosan, glucans, lentinans, and aminated polyglucose activate macrophages, important immune cells that engulf and destroy pathogens.

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    What is Immunosuppression?

    A type of immunomodulation where agents are used to reduce or dampen the immune response.

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    What is Non-specific Immunosuppression?

    Immunosuppression that affects multiple parts of the immune system, not targeting specific cells or processes.

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    How does Radiation work as an immunosuppressant?

    A non-specific immunosuppressant that damages DNA, preventing cell division. Used for cancer treatment and some autoimmune diseases.

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    What is the mechanism of Calcineurin Inhibitors?

    A class of drugs that act by inhibiting the synthesis of IL-2, a crucial signaling molecule in the immune system. Often used in organ transplantation to prevent rejection.

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    How do Corticosteroids work as immunosuppressants?

    A non-specific immunosuppressant that blocks the synthesis of cytokines and T cell responses. Used for inflammation and autoimmunity.

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    What is Selective Immunosuppression?

    Immunosuppression that targets specific parts of the immune system, like certain cells or processes, aiming for a more precise effect.

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    What is Immunopotentiation?

    A type of immunomodulation where agents are used to boost or strengthen the immune response.

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    What is the main target of Oclacitinib?

    Oclacitinib, a JAK inhibitor, primarily targets and inhibits JAK1, a key kinase involved in the production of various cytokines like IL-2, IL-4, IL-6, IL-13, and IL-31.

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    Study Notes

    Immunomodulation

    • Immunomodulation is the use of agents to either enhance or suppress the immune response.

    Learning Objectives

    • Define immunomodulation
    • Describe different types of immunomodulatory agents
    • Discuss immunosuppression (non-specific vs. selective)
    • Discuss immunopotentiation

    Immunomodulation Detail

    • Immunosuppression: Dampening the immune response

      • Non-specific immunosuppression

        • Radiation: Prevents cell division, damages DNA, and causes cell cycle arrest (G1/S checkpoint)
        • Corticosteroids: Stimulates the production of ΙκΒα, which inhibits NF-κB. This blocks cytokine synthesis and T-cell responses, creating anti-inflammatory and immunosuppressive effects. Corticosteroids also reduce gene transcription and cytokine synthesis.
        • Cytotoxic drugs (e.g., alkylating agents like Cyclophosphamide): Cross-link DNA to prevent cell division. Folic acid antagonists (e.g., Methotrexate): Block tetrahydrofolate production, which is necessary for thymidine and purine nucleotide synthesis. DNA synthesis inhibitors (e.g., Azatioprine): Inhibit DNA and RNA synthesis.

      • Selective immunosuppression

        • Calcineurin inhibitors (Cyclosporine and Tacrolimus): Inhibit IL-2 synthesis by forming complexes with cyclophilin and immunophilin, respectively, blocking calcineurin.
        • Rapamycin (Sirolimus): Forms a complex with immunophilin and blocks mTOR (mechanistic target of rapamycin). mTOR regulates cell metabolism, growth, proliferation, and survival.
        • JAK (Janus kinase) inhibitors (Oclacitinib): Inhibits JAK1, used to treat atopic dermatitis. This inhibits IL-2, IL-4, IL-6, IL-13, and IL-31.

    Stimulation of the Immune System

    • Bacterial products (Bacille Calmette-Guerin): Source of Pathogen-Associated Molecular Patterns (PAMPs), TLR stimulation, and cytokine synthesis.
    • Complex carbohydrates (Zymosan, Glucans, and Lentinans): Activate macrophages.
    • Vitamins (A, D, and E)
    • Cytokines (IL-2, recombinant IFNs (α & γ))

    BCG Vaccine

    • BCG vaccination induces enhanced production of cytokines, such as IL-1β, TNF-α, and IL-6. This process is associated with epigenetic reprogramming of monocytes and the production of pro-inflammatory cytokines (IL-1β, TNF and IL-6).
    • The effects are accompanied by epigenetic and metabolic reprogramming of myeloid cells in BCG-vaccinated individuals, creating "trained immunity." BCG vaccination can improve the immune response to subsequent viral challenges, leading to enhanced production of pro-inflammatory cytokines (IL-1β, TNF, and IL-6) during subsequent viral infections.

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