IMMUNOLOGY
Adverse events
ANTI-INFLAMMATORY
IMMUNOSUPPRESSIVE
100
What part of the immune system is affected by cell-mediated immunity? Main cell target?
Main: Macrophage
Complement (neutrophils)
CD8+
100
Which medication causes these AE?
Cyclosporine
100
Which 3 anti-inflammatories preferentially target Th1 pathways? What is their mechanism of action?
1) HCQ, Decreases MHC presentation in macrophages
2) Apremilast, PDE-4 inhibitor
Increases cAMP → decreased Th1 and Th17 cytokines
Th1: IFN-gamma + TNF-a
Th17: IL-23 and IL-17
3) Thalidomide/ Lenalidomide: Decreases Th1 cytokines (IL-12, IFN-gamma, TNF-a)
100
What are the 2 common side effects seen in all immunosuppressives? Why?
Increased infections/ malignancy
-- Decreased proliferation of lymphocytes either by decreased cytokines or DNA-synthesis
200
What are the different types of interferons and what are their functions?
1) Type 1 (a/b) --> antiviral/tumor, increase MHC I
2) Type 2 (gamma) --> Th1 response, increase MHC I and II
200
Medication? What is this feature called?
What other unique side effects seen with this medication?
Thalidomide (Phocomelia)
Other AE:
-- Thrombus
-- Peripheral neuropathy
-- Sedation
200
What causes the hematologic side effects in dapsone? Why is it worse with G6PD deficiency?
Hydroxylation of dapsone metabolites = potent oxidant --> increases oxidative stress that RBCs cannot withstand
-- Leads to hemolytic anemia and methemoglobinemia
-- G6PD is a potent anti-oxidant, deficiency worsens this AE
200
Which immunosuppressive does not have an increase in cancer risk?
Methotrexate
-- Likely due to its anti-proliferative quality
300
Key cytokines for each of the following:
Th1
Th2
Th17
Th1: IL-2, IFN-gamma, IL-12, TNF-a
Th2: IL 4,5,13, 31
Th17: IL-23, IL-17, IL-36 (also IL-6 and IL-1)
300
Medication?
HCQ
300
What are the 2 MOA for dapsone?
1) Inhibits myeloperoxidase → decreases oxidative damage
Affects neutrophils>eosinophils/ monocytes
Neutrophilic dermatoses
2) Inhibits dihydrofolate synthetase → disrupts folic acid pathway
Useful in treatment of leprosy
300
Which immunosuppressives decrease DNA synthesis?
What is the common side effect (1) from this process not seen in other immunosuppressives?
Bonus if you can state the MOA of each
1) Methotrexate : Inhibits dihydrofolate reductase
2) Azathioprine: Gets converted to 6-Thioguanine via the HGPT pathway
3) Mycophenolate: Inhibits inosine monophosphate dehydrogenase