Block E - Immunosuppression Flashcards
What are the three main types of non-specific immunosuppressants?
-False metabolites (e.g., Azathioprine)
-alkylating agents (e.g., Cyclophosphamide)
-inhibitors of nucleotide synthesis (e.g., Mycophenolic acid)
How does FK506 (Tacrolimus) differ from Cyclosporin A?
FK506 is 100 times more potent than Cyclosporin A and has lower nephrotoxicity.
What is the primary clinical use of cyclosporin A?
Prevention of transplant rejection by suppressing T-cell activation.
What is the mechanism of action of Rapamycin?
It inhibits mTOR, preventing T-cell proliferation and graft rejection.
What are some common side effects of non-specific immunosuppressants?
Hair loss, gastrointestinal damage, and skin damage.
Why does ALG lose effectiveness over time?
The body develops antibodies against it, reducing its effectiveness.
What is the key role of IL-2 in T-cell activation?
IL-2 promotes T-cell proliferation and immune response amplification.
How do steroids inhibit inflammation?
By inducing lipocortin, which inhibits phospholipase A2, reducing prostaglandin synthesis.
What was the significance of the discovery of Cyclosporin A in transplantation medicine?
It transformed organ transplantation from an experimental procedure into a viable long-term treatment.
What is the role of calcineurin in T-cell activation?
It dephosphorylates NFAT, allowing IL-2 transcription and T-cell proliferation.
Which of the following is NOT a type of non-specific immunosuppressant?
a) False metabolites
b) Alkylating agents
c) Cytokine inhibitors
d) Inhibitors of nucleotide synthesis
c) Cytokine inhibitors
Azathioprine functions as an immunosuppressant by:
a) Interfering with DNA synthesis as a false metabolite
b) Blocking calcium channels in T-cells
c) Stimulating the immune response
d) Increasing the production of cytokines
a) Interfering with DNA synthesis as a false metabolite
ALG (Anti-Lymphocytic Globulin) specifically targets:
a) B-cells
b) T-cells
c) Natural killer (NK) cells
d) Macrophages
b) T-cells
Cyclosporin A primarily inhibits:
a) IL-1 production
b) IL-2 production and T-cell activation
c) TNF-alpha signaling
d) Complement system activation
b) IL-2 production and T-cell activation
The main advantage of macrolides like FK506 (Tacrolimus) over Cyclosporin A is:
a) They are less potent than CsA
b) They have reduced nephrotoxicity
c) They are more effective against bacterial infections
d) They do not affect T-cell function
b) They have reduced nephrotoxicity
Rapamycin inhibits T-cell activation by targeting:
a) Calcineurin
b) mTOR
c) IL-1 receptors
d) NF-κB
b) mTOR
Which of the following is a side effect of non-specific immunosuppression?
a) Increased T-cell proliferation
b) Gastrointestinal damage
c) Enhanced antibody production
d) Increased resistance to infections
b) Gastrointestinal damage
Steroids suppress immune response by:
a) Blocking antigen presentation
b) Inducing lipocortin to inhibit phospholipase A2
c) Increasing prostaglandin synthesis
d) Enhancing leukocyte migration
b) Inducing lipocortin to inhibit phospholipase A2
What is the major limitation of ALG therapy?
a) It is ineffective in targeting lymphocytes
b) It eventually becomes ineffective due to antibody development
c) It is only effective in treating bacterial infections
d) It enhances cellular immunity
b) It eventually becomes ineffective due to antibody development
Mycophenolic acid suppresses the immune system by:
a) Inhibiting calcineurin
b) Acting as an allosteric inhibitor of nucleotide synthesis
c) Destroying B-cells
d) Blocking the complement system
b) Acting as an allosteric inhibitor of nucleotide synthesis
What is the primary mechanism by which cyclophosphamide exerts its immunosuppressive effects?
a) Intercalating DNA guanosines
b) Inhibiting IL-2 production
c) Blocking antigen presentation
d) Suppressing neutrophil activity
a) Intercalating DNA guanosines
Which of the following drugs acts as a non-competitive enzyme inhibitor?
a) Cyclosporin A
b) FK506 (Tacrolimus)
c) Mycophenolic Acid
d) Rapamycin
c) Mycophenolic Acid
What is the main difference between ALG and Cyclosporin A?
a) ALG targets circulating T-cells, whereas Cyclosporin A inhibits T-cell activation
b) ALG is a small molecule, whereas Cyclosporin A is an antibody
c) ALG is used for bacterial infections, whereas Cyclosporin A is used in viral infections
d) ALG has no side effects, whereas Cyclosporin A causes nephrotoxicity
a) ALG targets circulating T-cells, whereas Cyclosporin A inhibits T-cell activation
Which of the following statements about FK506 (Tacrolimus) is true?
a) It inhibits IL-1 signaling
b) It has no effect on T-cell activation
c) It binds to FKBP and inhibits calcineurin
d) It activates mTOR
c) It binds to FKBP and inhibits calcineurin
What is the key clinical advantage of Rapamycin over Cyclosporin A?
a) It prevents T-cell activation even after activation has occurred
b) It does not suppress IL-2 production
c) It enhances the immune response
d) It only targets B-cells
a) It prevents T-cell activation even after activation has occurred
Which immunosuppressive drug is most commonly associated with nephrotoxicity?
a) Mycophenolic Acid
b) Rapamycin
c) Cyclosporin A
d) ALG
c) Cyclosporin A
Which of the following is NOT a mechanism of immunosuppression by steroids?
a) Inhibiting prostaglandin synthesis
b) Enhancing cytokine production
c) Inducing lipocortin to inhibit phospholipase A2
d) Reducing inflammation
b) Enhancing cytokine production
ALG is derived from:
a) Human thymocytes
b) Large animal IgG fractions
c) Synthetic nucleotide analogs
d) Bacterial fermentation
b) Large animal IgG fractions
Which immunosuppressant is known to inhibit mTOR?
a) Cyclosporin A
b) FK506
c) Rapamycin
d) Mycophenolic Acid
c) Rapamycin
What was the key discovery that allowed Cyclosporin A to be used in transplantation?
a) It selectively inhibited IL-2 production in T-cells
b) It destroyed activated T-cells
c) It promoted graft rejection
d) It enhanced immune memory
a) It selectively inhibited IL-2 production in T-cells
What is a key difference between Cyclosporin A and FK506 (Tacrolimus) in terms of potency?
FK506 is about 100 times more potent than Cyclosporin A.
What are the major side effects of ALG?
Serum sickness, lymphoma at the injection site, and the development of anti-ALG antibodies.
What is the primary role of calcineurin in T-cell activation?
It dephosphorylates NFAT, allowing IL-2 transcription and T-cell proliferation.
What is the clinical significance of Mycophenolic Acid?
It inhibits nucleotide synthesis, suppressing T- and B-cell proliferation.
What is the primary difference between specific and non-specific immunosuppression?
Specific immunosuppression targets only certain immune cells (e.g., T-cells), whereas non-specific immunosuppression affects multiple cell types, leading to broader side effects.
How does Rapamycin function differently from FK506 and Cyclosporin A?
It inhibits mTOR instead of calcineurin, blocking T-cell proliferation after activation.
What role do steroids play in immunosuppression?
They inhibit inflammatory cytokines and prostaglandin synthesis by inducing lipocortin, which suppresses phospholipase A2.
Why does ALG become ineffective over time?
The body develops antibodies against it, neutralizing its effects.
What are the two pathways targeted by Cyclosporin A and FK506?
They both target calcium-dependent pathways involved in T-cell activation.
What is the function of FKBP in the mechanism of FK506 and Rapamycin?
FKBP binds to FK506 and Rapamycin, helping them interact with their respective targets (calcineurin for FK506 and mTOR for Rapamycin).
Which of the following is a characteristic of non-specific immunosuppression?
a) Targets only T-cells
b) Suppresses both innate and adaptive immunity
c) Has minimal side effects
d) Only affects B-cells
b) Suppresses both innate and adaptive immunity
Azathioprine functions as a prodrug that is converted into:
a) 6-mercaptopurine
b) Mycophenolic acid
c) Rapamycin
d) IL-2 antagonist
a) 6-mercaptopurine
The immunosuppressive effect of cyclophosphamide is due to:
a) Inhibition of NFAT activation
b) Alkylation of guanine residues in DNA
c) Blocking TNF-alpha
d) Suppression of IL-1 production
b) Alkylation of guanine residues in DNA
Which of the following is NOT a function of Cyclosporin A?
a) Inhibiting IL-2 transcription
b) Binding to cyclophilin
c) Inhibiting mTOR
d) Suppressing T-cell activation
c) Inhibiting mTOR
ALG therapy is limited because:
a) It is highly nephrotoxic
b) The body produces antibodies against it over time
c) It cannot be used for transplant rejection
d) It only affects the humoral immune response
b) The body produces antibodies against it over time
Mycophenolic acid blocks the synthesis of:
a) Purines
b) Pyrimidines
c) Peptidoglycans
d) IL-1 receptors
a) Purines
What is a major advantage of FK506 (Tacrolimus) over Cyclosporin A?
a) It has fewer side effects
b) It stimulates IL-2 production
c) It is 100 times more potent and causes less nephrotoxicity
d) It enhances antigen presentation
c) It is 100 times more potent and causes less nephrotoxicity
Which enzyme does Rapamycin target to exert its immunosuppressive effects?
a) Calcineurin
b) mTOR
c) Phospholipase A2
d) NF-κB
b) mTOR
The main disadvantage of using steroids for immunosuppression is:
a) They are too specific in their action
b) They can cause serious metabolic and immune system side effects
c) They do not inhibit inflammation
d) They only act on B-cells
b) They can cause serious metabolic and immune system side effects
Which of the following best describes how steroids suppress inflammation?
a) Blocking antigen presentation by macrophages
b) Stimulating B-cell proliferation
c) Inducing lipocortin, which inhibits phospholipase A2
d) Enhancing leukocyte migration to the inflammation site
c) Inducing lipocortin, which inhibits phospholipase A2
How do alkylating agents like cyclophosphamide suppress the immune system?
They crosslink DNA strands, preventing cell division and causing immune cell apoptosis.
What is the primary mechanism by which azathioprine suppresses the immune response?
It is converted into 6-mercaptopurine, which inhibits purine synthesis, blocking DNA replication in proliferating immune cells.
What is the function of calcineurin in T-cell activation?
It dephosphorylates NFAT, allowing IL-2 gene transcription and T-cell proliferation.
Why is Rapamycin considered an alternative to Cyclosporin A?
It prevents T-cell proliferation after activation by inhibiting mTOR, whereas Cyclosporin A prevents initial activation.
Why are steroids effective as immunosuppressants?
They inhibit the production of inflammatory cytokines and prostaglandins by blocking phospholipase A2 via lipocortin.
What major side effects are associated with Cyclosporin A?
Nephrotoxicity, hypertension, neurotoxicity, and increased risk of infections.
What is the function of FKBP in Tacrolimus (FK506) activity?
FKBP binds FK506, allowing it to inhibit calcineurin, blocking IL-2 transcription and T-cell activation.
What is the purpose of using ALG in immunosuppression therapy?
It targets and destroys circulating T-cells to suppress immune function, mainly used in transplant rejection prevention.
How does Mycophenolic Acid differ from Azathioprine in its mechanism?
Mycophenolic Acid specifically inhibits inosine monophosphate dehydrogenase (IMPDH), blocking purine synthesis, while Azathioprine acts as a false metabolite.
Why do immunosuppressive therapies increase the risk of infections and cancer?
They reduce the immune system’s ability to detect and destroy pathogens and abnormal cells.
Which immunosuppressant is a macrolide antibiotic that binds FKBP and inhibits mTOR?
Rapamycin (Sirolimus)
What is the primary reason why long-term steroid use is limited in immunosuppression?
Severe metabolic and endocrine side effects, including osteoporosis, adrenal suppression, and increased infection risk.
Explain how Cyclosporin A prevents T-cell activation at the molecular level.
Cyclosporin A binds cyclophilin, forming a complex that inhibits calcineurin, preventing NFAT dephosphorylation and IL-2 transcription.
Which immunosuppressive drug inhibits inosine monophosphate dehydrogenase and why is this significant?
Mycophenolic acid; it prevents guanine nucleotide synthesis, specifically targeting T- and B-cell proliferation.
Compare and contrast the mechanisms of FK506 and Rapamycin.
Both bind FKBP, but FK506 inhibits calcineurin (blocking IL-2 production), while Rapamycin inhibits mTOR (blocking T-cell proliferation after activation).
What are the main pharmacokinetic differences between Cyclosporin A and FK506?
FK506 is more potent, has better tissue penetration, and causes less nephrotoxicity compared to Cyclosporin A.
Describe why ALG is effective in acute transplant rejection but not for long-term therapy.
ALG depletes circulating T-cells but is limited due to the development of anti-ALG antibodies over time.
Which immunosuppressive strategy specifically prevents signal transduction through IL-2 receptors?
Rapamycin (Sirolimus) by inhibiting mTOR, which is essential for IL-2 receptor signaling.
How does Mycophenolate Mofetil differ from traditional alkylating agents in immunosuppression?
Mycophenolate Mofetil inhibits purine synthesis rather than directly damaging DNA, making it more selective for lymphocytes.
Which enzyme do corticosteroids upregulate to inhibit phospholipase A2 activity?
Lipocortin-1 (Annexin-1)
Which immunosuppressant specifically inhibits JAK-STAT signaling?
Tofacitinib
What is the main difference between Basiliximab and Daclizumab in terms of IL-2 receptor blockade?
Basiliximab is a chimeric monoclonal antibody, while Daclizumab is a humanized monoclonal antibody.
Which drug inhibits proteasome activity and is used in multiple myeloma as an immunosuppressant?
Bortezomib
Which immunosuppressive agent is a fusion protein that blocks CTLA-4 to prevent T-cell activation?
Abatacept
Why does Sirolimus (Rapamycin) not cause nephrotoxicity like Calcineurin inhibitors?
It inhibits mTOR, which affects cell cycle progression rather than direct nephrotoxic effects on kidney cells.
Explain how JAK inhibitors suppress immune responses at the molecular level.
JAK inhibitors prevent cytokine receptor-mediated phosphorylation of STAT proteins, blocking transcription of inflammatory genes.
Which immunosuppressant targets CD52, leading to depletion of both B and T cells?
Alemtuzumab
Why does blocking CTLA-4 enhance immune activation rather than suppress it?
CTLA-4 normally downregulates T-cell activation; blocking it leads to increased immune activation rather than suppression.
What role do Regulatory T-cells play in maintaining immune homeostasis?
Regulatory T-cells suppress excessive immune activation through IL-10 and TGF-β, maintaining tolerance to self-antigens.
How does Eculizumab function in suppressing immune responses, and which pathway does it target?
Eculizumab blocks complement protein C5, preventing formation of the membrane attack complex (MAC) and reducing immune-mediated lysis.
