Immunopharmacology Flashcards
What are the main uses of immunosuppressive drugs?
Prevent transplant rejection and to treat AI disease
Mechanism of rejection:
Dendrite cells (antigen presenting cells) go into the transplanted organ and take up Ag to present them to T cells in lymph nodes (CD4+ cells). These produce cytokines like IL2, which drive T cell proliferation during immune response. End result is a dramatic expansion in immune cells, which attack the transplanted organ.
What do dendritic cells have that allows them to present to Ag to the T cell?
MHC2 on their surface
What must also be present when the T cell recieves the antigen? What is this complex called?
a co receptor and IL 1 signal
Immune synapse
What happens when the T cell is activated?
There is an increase intracellular calcium which turns on protein phosphotase called calcineurin
What does calcineurin do? What is this significance?
Dephosphorylates proteins like NFAT (transcription factor). This allows it to enter the cell and transcribe IL2.
What role does IL 2 have?
Feeds back to T cells, activates mTOR in T cells, which is protein kinase. Leads to T cell proliferation
What is the role of prednisone?
Immunosuppressive because it blocks cytokine production (IL1), prevents T cell activation
What do rapamycin and sirolimus block?
The both block mTOR and sirolmus also binds to FKBP further decreasing mTOR
What are the side effects of sirolimus and rapamycin?
Stomatitis and hyperlipidemia
What do tacrolimus and Cyclosporine block?
calcineurin by bindign to FKBP and Cyclophilin
What are the side effects of tacrolimus and cyclosporine?
Kidney and liver toxicity
How long are transplanted patients on tacrolimus and cyclosporine?
For life, if severe side effects switched to sirolimus
Cyclophosphamide
non specific way to block proliferation, its heavily toxic and not good for long term treatment only acute
Methotrexate
Use to treat RA and can be used as a non specific way to block proliferation
Mycophenolate mofetil
Blocks nucleic acid synthesis, great for immunosupression b/c selectivity to T cells
What are some toxicities due to proliferation?
Hair loss, GIT problems and myelosuppression
What is OKT3?
A mouse antibody that is used to treat rejection, only short term though because humans have an immune response to it
How do we fix a Rh - prego with her second Rh + baby?
Give her RHOGAM with in 72 hours to kill immune exposed cells to keep mom naive
T/F When presented with the same antigen 2 animals will present different ABs.
True
How do you prevent the death of B cells that are specific to a given Ag when they are taken out of the spleen?
Fuse them with a CA cell line so they proliferate and are immortal
CD3 (OKT-3)
Muromonab- binds CD3 on the surface of T cells and inhibits T cell function. Used to treat acute transplant reduction.
Anti-IL2 receptor antibodies
Daclizumab- Blocks IL-2 receptor activation, thus blocking T cell activation; Used to treat acute transplant rejection
Rituximab
Chimeric monoclonal antibody against the CD20 B-cell antigen
•Used to treat relapsed indolent lymphomas
•Approved for the treatment of Rheumatoid Arthritis when combined with methotrexate
•May be useful in the treatment of Multiple Sclerosis
