Autoimmune Flashcards
What is an autograft?
Cells taken from a patient and then put onto a different part of the same patient
Leukemia, skin graft
What is an allograft?
Cells or tissue transplanted from another person
What is a xenograft?
Cells or tissue transplanted among species (human tumor into a mouse)
What are the different types of graft rejection?
Hyperacute: Occurs in minutes
Acute: 7-21 days
Chronic: 3 months
How does specific immunity against organ transplantation (GVHD) occur?
Foreign organ proteins are engulfed and presented by macrophages or other antigen presenting cells which stimulates Th cells to activate B cells form antibodies against the foreign proteins. The antibodies will then cause neutralization, opsonization and phagocytosis to help rejection
How does the helper T cell activate the B cells?
Interacts with the B cell and releases cytokines, which activate the B cells
Interleukins
How are antibodies formed?
The activated B cell proliferates into clones which then proliferate and differentiate into antibody secreting cells and memory cells
How does cyclosporine work?
Binds to the protein cyclophilin and their complex inhibits calcineurin/NF-AT activation (phosphorylation of NF-AT) and blocks IL-2 gene transcription (inhibits IL-2 release and expression of their receptors)
Decreases activation of T cells
Induction phase
What are the pharmacokinetics of cyclosporine?
Oral, IV
Oral absorption is slow and incomplete
T1/2 is about 24 hours
Concentrated in peripheral tissue (lymphomyeloid, adipose tissue)
What are the adverse effects of cyclosporine?
Nephrotoxicity, hypertension, increased risk of infection, liver dysfunction (monitor)
What are the drug interactions with cyclosporine?
Inhibit metabolism: Ca channel blockers, azoles, mycin, grapefruit juice
Induce metabolism: Phenytoin, anti-TB drugs (isoniazid, rifampin)
How does tacrolimus work?
Binds to FK binding protein (FKBP) which inhibits calcineurin phosphatase which decreases activation of transcription factor (NF-AT) and decreases IL-2 gene transcription
Induction phase
How does sirolimus work?
Binds to intracellular immunophilins but does not block IL-2 gene transcription, but instead interferes with IL-2 signal transduction pathway to activate cell proliferation in activated T cells
How does mycophenolate mofetil work?
Inhibits inosine 5’-monophosphate dehydrogenase (crucial enzyme in purine synthesis) which inhibits T and B cell proliferation
What are the pharmacokinetics of mycophenolate mofetil?
Converted to mycophenolic acid
Mg and Al impair absorption
Metabolites undergoes enterohepatic circulation
What is mycophenolate mofil indicated for?
Transplant recipients with cyclosporine and steroids
How does azathioprine work?
Metabolized to 6-MP (anticancer)
Inhibits the HGPRT enzyme which is important in purine synthesis
Cytotoxic to dividing cells
What is azathioprine indicated for?
IV loading dose on day of transplant
Oral for maintenance
Used in combo with other immunosuppressant drugs for kidney, liver transplants and RA
What is the major side effect of azathioprine?
Bone marrow depression
How does cyclophosphamide work?
A nitrogen mustard (alkylating agent) prodrug whose alkyl groups cross react with 2 DNA nucleophilic sites (guanine) to inhibit DNA replication
What is cyclophosphamide used for?
Lupus and RA