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25 Cards in this Set
- Front
- Back
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What is the difference between Host vs Graft disease and Graft vs Host disease?
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Proliferation of host anti-graft cells vs. proliferation of graft anti-host cells. Duh.
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What are the pre-conditions for GVHD?
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Recipient and host are immunologically disparate i.e. histoincompatible.
Graft is immuno-competent with viable and functional immune cells Recipient is immune compromised and therby cannot destroy, inactivate or replace transplanted cells. |
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What are the three stages of immunosuppressive treatmetnt in solid organ transplant and the treatment needed,
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Early/acute rejection - Basiliximab
Late rejection - Tacrolimus, MMF & steroid Chronic rejection - Tacrolimus |
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What immunosuppressive treatment is required after a BM transplant?
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Conditioning therapy (to prevent rejection of bone marrow
Tx to prevent GVHD Immune suppression (nil after 6 months) |
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Why can we cease immunosuppression 6 months after BM transplant but not after solid organ transplant.
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BM contains T cell progenitors that will migrate to thymus, become centrally educated. Those that are auto (i.e. host reactive) will be negatively selected leaving only a repertoire of completely self-tolerant T cells.
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What are the effects of glucocorticoids?
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Broad anti-inflammatory effects:
Decrease PBMC count Downregulation of IL-1, -6 --> inhibition of T cell proliferation Down regulation of immune cell receptors. |
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What are the side effects of glucocorticoids?
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Emotional disturbance
Cushingoid appearance (moon face, buffalo hump, central obesity, peripheral wasting) Amenorrhoea |
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How does cyclosporin work?
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By binding cyclophillin that in turn inhibits calcineurin. Without calcineurin, there is no IL-2 transcription and inhibition of T cell proliferation.
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How does tacrolimus work?
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By binding FKBP that in turn inhibits calcineurin. Without calcineurin, there is no IL-2 transcription and inhibition of T cell proliferation.
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What are the side effects of cyclosporin and tacrolimus?
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Renal dysfunction, hypertension and increase risk of tumours and infections.
In addition to this, tacrolimus has a smaller therapeutic window than cyclosporin and therefore has a greater risk of toxicity. |
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What enzyme metabolises cyclosporin, tacrolimus and evorilimus?
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CYP3A4.
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What is mycophenolate mofetil (MMP) and how does it work?
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It is an antiproliferative/anti-metabolic drug. It inhibits IMPDH, the enzyme that catalyses conversion of sugar to GMP (specifically in lymphocytes)
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What are the side effects of MMP?
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Toxicity (GI, diarrhoea and haematological, leucopaenia) and increased risk of infection.
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When is MMP used?
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As a prophylaxis in conjunction with glucocorticoids and a calcneurin inhibitor e.g tacrolimus.
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What is mTOR?
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The engine room of the cell, it decides whether the cell has enough nutrients O2 etc for T cell to safely undergo division.
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What are sirolimus and everilimus?
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mTOR inhibitors.
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What are the side effects of sirolimus and everilimus?
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Abnormal liver profile (decrease in serum cholesterol, platelets and RBCs), fever and risk of infection.
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When are siroliums and everilmus used?
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In those intolerant of calcineurin inhbitors such as tacrolimus and cyclosporin.
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What are used in the prophylaxic of acute organ rejection?
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IL-2RA e.g. Basiliximab and Daclizumab. Importantly are NON-depleting.
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What do you use in the eare intense phase after solid organ transplant?
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Alemtuzumab; anti-CD-52 that depletes T, B, NK and APCs.
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What is bortezomib?
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A proteasome inhibitor. By inhibiting NF-kB it leads to decreased B cell activation and decrease in humoural rejection,
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What is belatacept?
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Fc portion of IgG1 fused to CTLA-4. Same as abatacept but differs by two a.a. More specific for providing extended graft survival wherease abatacept is indicated for RA.
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What is alefacept?
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Immunosuppressive drug that interferes with CD2 on T cell and prevents its interaction with LFA-3 on APC and thus interfering with T cell activation.
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Infectious complications: what do you get as a result of decreased CD8+ T cell response.
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CMV pneumonitis
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Infectious complications: what do you get as a result of decreased CD4+ T cell response.
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Shingles i.e. reactivation of a dormant VZV infection.
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