Podcast
Questions and Answers
Which of the following best describes the role of calcineurin in T-cell activation?
Which of the following best describes the role of calcineurin in T-cell activation?
- It activates calmodulin, which then inhibits T-cell proliferation.
- It directly binds to DNA, inducing the transcription of IL-2 and other cytokines.
- It dephosphorylates NFAT, allowing it to enter the nucleus and promote cytokine production. (correct)
- It phosphorylates NFAT, preventing its translocation into the nucleus.
How do cyclosporine and tacrolimus exert their immunosuppressive effects?
How do cyclosporine and tacrolimus exert their immunosuppressive effects?
- By forming complexes that inhibit calcineurin's phosphatase activity. (correct)
- By binding directly to NFAT, preventing its activation.
- By directly inhibiting the T-cell receptor (TCR).
- By promoting the phosphorylation of NFAT, keeping it active in the cytoplasm.
What is the immediate consequence of calcineurin inhibition on NFAT?
What is the immediate consequence of calcineurin inhibition on NFAT?
- NFAT remains phosphorylated and stays in the cytoplasm. (correct)
- NFAT is dephosphorylated and translocates into the nucleus.
- NFAT activates calmodulin, leading to further T-cell activation.
- NFAT binds to DNA and starts the transcription of IL-2.
Which of the following events would directly follow the stimulation of the T-cell receptor (TCR) in a normal T-cell activation pathway?
Which of the following events would directly follow the stimulation of the T-cell receptor (TCR) in a normal T-cell activation pathway?
If a patient is taking tacrolimus, which of the following processes would be directly inhibited?
If a patient is taking tacrolimus, which of the following processes would be directly inhibited?
What is the role of immunophilins like cyclophilin and FKBP-12 in the mechanism of action of calcineurin inhibitors?
What is the role of immunophilins like cyclophilin and FKBP-12 in the mechanism of action of calcineurin inhibitors?
In a T-cell treated with cyclosporine, what would be the expected state and location of NFAT?
In a T-cell treated with cyclosporine, what would be the expected state and location of NFAT?
Which cytokine's transcription is most directly affected by the inhibition of NFAT translocation into the nucleus?
Which cytokine's transcription is most directly affected by the inhibition of NFAT translocation into the nucleus?
A researcher is studying a new drug that also inhibits T-cell activation. If this drug works similarly to cyclosporine, which of the following mechanisms of action would be most likely?
A researcher is studying a new drug that also inhibits T-cell activation. If this drug works similarly to cyclosporine, which of the following mechanisms of action would be most likely?
How does the function of calcineurin contribute to the adaptive immune response?
How does the function of calcineurin contribute to the adaptive immune response?
Flashcards
Calcineurin
Calcineurin
A calcium and calmodulin-dependent phosphatase crucial for T-cell activation. It dephosphorylates NFAT, allowing it to enter the nucleus and promote cytokine production.
Calcineurin Inhibitors (CNIs)
Calcineurin Inhibitors (CNIs)
Drugs like cyclosporine and tacrolimus that prevent T-cell activation by inhibiting calcineurin's phosphatase activity.
Nuclear Factor of Activated T-cells (NFAT)
Nuclear Factor of Activated T-cells (NFAT)
A protein that, when dephosphorylated by calcineurin, translocates to the nucleus to promote the transcription of IL-2 and other cytokines.
Cyclophilin
Cyclophilin
Signup and view all the flashcards
FKBP-12 (FK506-binding protein)
FKBP-12 (FK506-binding protein)
Signup and view all the flashcards
Phosphorylated NFAT (inactive)
Phosphorylated NFAT (inactive)
Signup and view all the flashcards
T-cell Receptor (TCR)
T-cell Receptor (TCR)
Signup and view all the flashcards
Calmodulin
Calmodulin
Signup and view all the flashcards
IL-2
IL-2
Signup and view all the flashcards
Calcineurin Inhibition
Calcineurin Inhibition
Signup and view all the flashcards
Study Notes
- Calcineurin is a calcium and calmodulin-dependent serine/threonine phosphatase critical for T-cell activation.
- It dephosphorylates nuclear factor of activated T-cells (NFAT), enabling it to enter the nucleus.
- Once in the nucleus NFAT promotes the transcription of IL-2 and other cytokines, which are essential for T-cell proliferation.
Mechanism of Action of Calcineurin Inhibitors in Immunosuppression
- Calcineurin inhibitors (CNIs) like cyclosporine and tacrolimus prevent T-cell activation thus reducing the immune response.
Normal Calcineurin Function (Without Inhibitors)
- In resting T-cells, NFAT is phosphorylated (inactive) and remains in the cytoplasm.
- Immunophilins are freely found in the cytoplasm and have no effect on NFAT.
- When the T-cell receptor (TCR) is stimulated by an antigen intracellular calcium levels rise, leading to activation of calmodulin.
- Calmodulin activates calcineurin, a serine/threonine phosphatase.
- Calcineurin dephosphorylates NFAT, activating it and enabling it to translocate into the nucleus.
- Once in the nucleus, NFAT binds to DNA and induces the transcription of IL-2 and other cytokines, promoting T-cell proliferation.
Mechanism of Action of Calcineurin Inhibitors (Cyclosporine & Tacrolimus)
- Cyclosporine binds to cyclophilin, and tacrolimus binds to FKBP-12 (FK506-binding protein).
- The drug-immunophilin complexes bind to calcineurin, inhibiting its phosphatase activity.
- By inhibiting calcineurin, the complexes prevent calcineurin from dephosphorylating NFAT.
- Since NFAT remains phosphorylated, it cannot translocate into the nucleus.
- Without NFAT in the nucleus, IL-2 transcription is blocked, leading to reduced T-cell activation and proliferation.
Studying That Suits You
Use AI to generate personalized quizzes and flashcards to suit your learning preferences.
