14. Targeting Immune Disorders Flashcards
Name 3 stimulatory cytokines
IL-1
IL-2
TNF
Name 2 inhibitory cytokines
IL-3
IL-4
Name a class of cell adhesion molecules
Integrins
What is the role of ERVs in organ transplant?
Increases risk when transplanting an organ from a non-human animal
Virus is endogenous to that species, but can be incorporated into human DNA
What type of antigens are responsible for graft vs host disease?
Histocompatible
What part of the immune system is activated by xenografts from animals?
Complement
Name 3 classes of cytotoxic immunosuppressants
Alkylating agents
Folic acid analogues
Purine derivatives
Name an alkylating agent
Cyclophosphamide
What is cyclophosphamide activated to in the liver?
Phosphamide mustard
What immune reaction does cyclophosphamide cause?
Absolute leucopaenia
What effect does low dose cyclophosphamide have on the immune system?
Targets only B cells
What are the side effects of cyclophosphamide?
Alopecia
Nausea
Name an anti-folate
Methotrexate
What is the MOA of methotrexate?
Interferes with dihydrofolate reductase
Inhibits replication of B and T cells
What diseases is methotrexate used to treat?
RA
Psoriasis
Why is the low dose used to treat rheumatoid arthritis not effective in cancer?
At this dose it doesn’t affect DHF reductase
Instead it increases adenosine production which has anti-inflammatory effects
What causes the side effects associated with methotrexate?
Lack of folic acid
Immune suppression
Name an anti-cancer agent which is used to treat MS
Mitoxantrone
What is the MOA of mitoxantrone?
Intercalates into DNA and inhibits topoisomerase 2
Why is mitoxantrone used as a last resort treatment?
Cardiotoxicity
Which antibiotics have immune suppressive effects?
Doxorubicin
Daunorubicin
Which cells are inhibited by doxorubicin?
B cells more than T cells
Doesn’t inhibit macrophages or NKs
Which cells are inhibited by Daunorubicin?
Macrophages
What is the serious side effect of doxorubicin?
Cardiomyopathy
Name a purine analogue used in immunosuppression
Azathioprine
What is azathioprine metabolised to?
Mecaptopurine which inhibits DNA synthesis
Which parts of the immune system are suppressed by azathioprine?
Both humoral and cellular
Inhibits phagocytes
Causes monocytopaenia
No effect on NKs
What disease is azathioprine used to treat?
With prednisone to prevent organ transplant rejection
Which drug targets guanine synthesis?
Mycophenolate mofetil
What disease is mycophenolate mofetil used to treat?
Combined with calcineurin inhibitors to treat kidney transplant
What is the MOA of leflunamide?
Inhibits enzyme for pyrimidine synthesis
Inhibits B and T cells
What diseases is leflunomide used for?
RA
Active metabolite, terilunomide used in MS
What is the MOA of cladribine?
Inhibits adenosine deaminase
What disease is cladribine used to treat?
Hairy cell leukaemia
What is the MOA of glucocorticoids?
Increase lipocortin production which inhibits phospholipase A2
What effect do glucocorticoids have on immune mediators?
Reduce IL1, IL2, IFN, prostaglandins and leucotrienes
What effect do glucocorticoids have on immune cells?
Reduced basophils, eosinophils, monocytes and lymphocytes
Increased neutrophils
What adverse effect is associated with glucocorticoids?
Impairs carbohydrate metabolism
