Transplantation

Objectives first paragraph subtitles bold-faces, colored, italicized print shaded areas or boxed information diagrams, charts, graphs, tables...concepts lists pictures, drawings new terms summary first sentances

organs and tissues transpaltnted, stats fo rgraft survival for organs from related, cadaveric donors criteria used to establish death for purposes of organ, tissue donation acceptable, exclusionary criteria donation each organ methods oorgan preservation: recovery of kidney, liver, pancreas, heart, lu g. accpeptable intervalse for preservation autograft, isograft, allograft, xenograft, orthotobpic graft, hertertopic graft current forms of immunosuppresion for transplatntaion, describe mechanisms of action, specific side effects hyperacute, acceleratated acute, acute, chronic rejection in tehrms fo pathophys, timing, histology, prognosis

Goals: Dr. Norman
- You should be aware of the big concepts about transplant demographics and recipient selection and contraindications.
 * Know that ESRD is epidemic
 * know the financial costs of dialysis
 * Describe the mortality rate of ESRD
 * Know the benefits of kidney transplant
 * Know the benefits of kidney & pancreas transplantation

Goals: Dr. Magee
- You should know generally why transplanted organs are rejected and the roles of the major cells involved, i.e. antigen presenting cells and lymphocytes as well as the types of rejection that can occur. You don’t need to study any detailed pathways of antigen presentation or cellular signalling.

Goals: Dr. Johnson
- You should know how to distinguish between the different forms of transplant rejection. You should appreciate the characteristics of tubulointerstitial nephritis. Both of these areas are also covered in the Clinicopathological Labs the afternoon of the lecture. You should be aware of the existence of the disease processes mentioned on pages 351-360 of the course pack.

Goals: Dr. Cibrik
- You should know the differences between induction, maintenance, and treatment of acute rejection and the major drugs used for each as given in the syllabus. - You should know the distinctive characteristics of steroids, azathioprine, mycophenolate and the calcineurin inhibitors (by their generic names), the emphasized factors that impact on their metabolism, and the most important form of toxicity of each that was discussed in lecture. - You do not need to know the fine details of the T cell activation pathways involved in their effects or to distinguish among the various new antibodies becoming available.
 * Describe 3 signals for T-cell activation
 * Know commonly used immunosuppressant agents
 * Describe the pharmacological mechanisms of each drug
 * Know the common side effects of immunosuppressant drugs
 * Name || Use || Mechanism || Side Effects ||
 * Prednisone ||  || inhibit broad range of cytokine transcription || ostteoporosis, weight gain, yhyyperglycemia, cushing's ||
 * Azathioprine || Maintenance anti-proliferative agent || inhibits both scavenged and de novo purine biosynthesis || **pancreatitis, alopecia, hepatotoxic, veno-occlusive liver disease** ||
 * Mycophenolate || Maintenance anti-proliferative agent || selective inhibitor of de novo purine biosynthesis || cytopenias, GI toxic ||
 * Rapamycin || maintenance anti-proliferative agent || p4revents cell division-binds to protein, prevents change from G1 to S phase || hyperlipidemia, cytopenia, nephrotoxic? ||
 * Cyclosporine || maintenance calcineurin inhibitor || binds to cyclophilin, which inhibhits calcineurin phosphatase, prventing IL2 gene transcription || nephrotoxic, neurotoxcic, HTN, hyperlipidemia, **hisrtutism** ||
 * Tacrolimus || maintenance calcineurin inhibitor || Binds to FKBP,, inhibits calcineurin phosphatase, then inhibits IL2 transcription || Inhibits CYP3A4 nephrotoxic, neurotxic HTN, hyperglycemia**, Alopecia** ||
 * Daclizumab || induction || humanized a-IL2; binds CD25 on activated T cells || Fever, cytopenia, viral infections, malignancies ||
 * Basiliximab || induction || chimeric a-IL2; binds CD25 on activated T cells || Fever, cytopenia, viral infections, malignancies ||
 * OKT3 || induction || murine a-CD3; clears lymphocytes || Fever, cytopenia, viral infections, malignancies ||
 * Rabbit a-T IgG || induction ||  || Fever, cytopenia, viral infections, malignancies ||
 * Horse a-T IgG || induction ||  || Fever, cytopenia, viral infections, malignancies ||
 * Rituximab || Treatment off acutre rejection || a-CD20 monoclona; against B cells || Fever, cytopenia, viral infections, malignancies ||

Induction: OKT3, a-IL2, rATG, hATG maintenance: corticosteroids, anti=proliferateive agents, calcineurin inhibitors

anti-proliferative agents: azathioprine, mycophenolate, rapamycin

calcineurin inhibitors: cyclosproine, tacrolimus