Pharmacology - IMMUNOSUPPRESSANTS (MADE EASY)

Speed Pharmacology
3 Jan 202209:49

Summary

TLDRThis lecture provides an in-depth overview of the pharmacology of immunosuppressants, detailing the complex workings of the immune system, which includes both innate and adaptive immunity. It explains the mechanisms of action for various classes of immunosuppressive drugs, including calcineurin inhibitors, costimulation blockers, mTOR inhibitors, antimetabolites, corticosteroids, and antibodies. The lecture emphasizes the importance of these medications in managing autoimmune diseases and preventing transplant rejection by disrupting T-cell activation. Overall, it highlights how these drugs play a crucial role in regulating immune responses.

Takeaways

  • 🛡️ The immune system has two levels: innate immunity (non-specific and fast-acting) and adaptive immunity (specific and slower).
  • 🦠 Innate immunity involves various cells, including natural killer cells, macrophages, and dendritic cells, which recognize pathogens through receptors.
  • 🔗 The adaptive immune system consists of humoral immunity (mediated by B cells producing antibodies) and cellular immunity (mediated by T cells).
  • 🧬 T cells recognize specific antigens on antigen-presenting cells (APCs) using their T cell receptors (TCR), initiating adaptive immune responses.
  • ⚛️ T cell activation requires a two-signal process: recognition of the antigen by TCR and a secondary costimulation signal from CD28 binding to CD80/CD86.
  • 📈 Activated T cells produce cytokines, including interleukin-2 (IL-2), promoting further T cell proliferation and activation of other immune cells.
  • 💊 Immunosuppressive drugs are crucial for managing autoimmune diseases and transplant rejection by disrupting T cell activation.
  • ⚖️ Calcineurin inhibitors, like Cyclosporin and Tacrolimus, prevent NFAT from entering the nucleus, impairing IL-2 transcription.
  • 🚫 Costimulation blockers (e.g., Belatacept and Abatacept) prevent complete T cell activation by blocking interactions between CD28 and APCs.
  • 🧪 mTOR inhibitors (Sirolimus and Everolimus) halt cell cycle progression and IL-2 response by inhibiting mTOR activity.
  • 📉 Antimetabolites (Azathioprine and Mycophenolate mofetil) disrupt DNA synthesis and cell proliferation through different mechanisms.
  • 🏥 Corticosteroids (Prednisone, Prednisolone, and Methylprednisolone) regulate T cell responses and alter gene transcription to induce immunosuppression.
  • 🧬 Antithymocyte globulins and Basiliximab are antibody products used to prevent transplant rejection by inducing T cell death or inhibiting IL-2-driven proliferation.

Q & A

  • What are the two levels of immunity in the human immune system?

    -The two levels of immunity are innate immunity, which is non-specific and fast-acting, and adaptive immunity, which is more specific and slower to respond.

  • What role do natural killer cells play in the immune system?

    -Natural killer cells are involved in the innate immune response, acting as the primary line of defense against pathogen invasion.

  • How do T cells recognize antigens?

    -T cells recognize antigens through their T cell receptors (TCR) as they bind to antigens presented by antigen-presenting cells (APCs) in conjunction with major histocompatibility complex (MHC) molecules.

  • What is the significance of interleukin-2 (IL-2) in T cell activation?

    -IL-2 is a major growth factor that promotes the proliferation of antigen-primed T cells and activates other immune cells, playing a crucial role in the adaptive immune response.

  • What are calcineurin inhibitors, and how do they function?

    -Calcineurin inhibitors, such as Cyclosporin and Tacrolimus, bind to immunophilins and inhibit calcineurin, preventing NFAT from translocating to the nucleus and thus impairing IL-2 gene transcription.

  • What is the mechanism of action for costimulation blockers like Belatacept and Abatacept?

    -Costimulation blockers selectively bind to CD80 and CD86 on APCs, preventing their interaction with CD28 on T cells, which inhibits complete T cell activation, reducing T cell proliferation and IL-2 production.

  • How do mTOR inhibitors, such as Sirolimus and Everolimus, affect T cell activity?

    -mTOR inhibitors bind to FK-binding proteins but instead inhibit mTOR activity, slowing or halting cell cycle progression and inhibiting the cellular response to IL-2.

  • What is the role of corticosteroids in immunosuppression?

    -Corticosteroids mediate immunosuppression by regulating T cell responses, inhibiting key transcription factors, and causing rapid dissociation of T-cell-receptor-associated protein complexes.

  • What is the mechanism of action of antibodies used in transplantation?

    -Antibodies like antithymocyte globulins induce cell death in T cells via complement-mediated cytotoxicity or apoptosis, while monoclonal antibodies like Basiliximab inhibit IL-2 driven T cell proliferation.

  • What are the potential consequences of deregulated immune responses?

    -Deregulated immune responses can lead to chronic inflammatory diseases such as autoimmunity and cancer, as well as serve as a barrier for organ transplantation.

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الوسوم ذات الصلة
ImmunologyPharmacologyImmunosuppressantsT-cell ActivationAutoimmunityTransplantationMedical EducationDrug MechanismsHealth CarePatient Care
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