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

    What is the primary function of immunomodulation?

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

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

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

    What type of immunosuppression does the drug cyclosporine provide?

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

    Which of the following describes the action of corticosteroids?

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

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

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

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

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

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

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

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

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

    What type of signaling does JAK-STAT primarily influence?

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

    What is the main purpose of immunomodulation?

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

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

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

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

    <p>IL-2</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.</p> Signup and view all the answers

    What characterizes selective immunosuppression?

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

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

    <p>Methotrexate</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.</p> Signup and view all the answers

    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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