Transplant and Immunology

CHAPTER 3
Transplant and Immunology


Arjumand Ali


Test Taking Tips


Topics related to transplant are usually memorization-based.


Quickly review transplant medications and the types of rejection the night before the test.


INTERLEUKINS


Name the cells of origin and functions of the following interleukins:


Interleukin-1


• Mononuclear phagocytes, T and B cells, NK, cells fibroblasts, neutrophils, smooth muscle cells


• Proliferation of T and B cells; fever, inflammation; endothelial cell activation; increases liver protein synthesis


Interleukin-2


• Activated T cells


• T-cell growth factor, cytotoxic T-cell generation; B-cell proliferation/differentiation; growth/activation of NK cells


Interleukin-4


• CD4+ T cells, mast cells


• B-cell activation/differentiation, T- and mast cell growth factor


Interleukin-5


• T cells


• Eosinophil proliferation/activation


Interleukin-6


• Mononuclear phagocytes, T cells, endothelial cells


• B-cell proliferation/differentiation; T-cell activation; increases liver acute phase reactants; fever, inflammation


Interleukin-8


• Lymphocytes, monocytes, multiple other cell types


• Stimulates granulocyte activity, chemotactic activity; potent angiogenic factor


Interleukin-10


• Mononuclear phagocyte, T cells


• B-cell activation/differentiation, inhibition, mononuclear phagocytes


Interleukin-12


• Mononuclear phagocytes, dendritic cells


• IFN-γ synthesis, T-cell cytolytic function, CD4+ T-cell differentiation


INTERFERONS AND OTHER CHEMOKINES


What cells produce interferon-γ and what are its functions?


• NK and T cells


• Increases expression of class I and class II MHC, activates macrophages and endothelial cells, augments NK activity, antiviral


What cells produce interferon-α, β and what are their functions?


• Mononuclear phagocyte-α; fibroblast-β


• Mononuclear phagocyte increases class I MHC expression, antiviral, NK-cell activation


What cells produce tumor necrosis factor-α, β and what are their functions?


• NK and T cells, mononuclear phagocyte


• B-cell growth/differentiation, enhances T-cell function, macrophage activator, neutrophil activator


What cells produce transforming growth factor-β and what are its functions?


• T cells, mononuclear phagocyte


• T-cell inhibition


What cells produce lymphotoxin and what are its functions?


• T cells


• Neutrophil activator, endothelial activation


IMMUNOSUPPRESSANTS


What was the first effective clinical immunosuppressive regimen for the transplantation of solid organs? (It was introduced in 1962.)


Azathioprine and corticosteroids


What are the 2 commercially available antilymphocyte globulins used for induction immediately after transplantation?


Horse antithymocyte globulin; rabbit antithymocyte globulin (most commonly used)


What is OKT3?


A monoclonal antibody that binds to CD3, a site associated with the TCR, that blocks cell-mediated cytotoxicity by inhibiting the function of naive T cells and established cytotoxic lymphocytes


What may be seen with the first or second dose of OKT3?


Acute cytokine release syndrome; avoid with concomitant administration of steroids or indomethacin


What 2 monoclonal antibodies that became available in 1998 decrease rejection by leaving cells with no free receptors for IL-2 to bind by binding to the IL-2R without activating it?


Basiliximab; daclizumab


Table 3-1 Summary of the Main Immunosuppressive Drugs


Image


What is rituximab?


An anti-CD20 monoclonal antibody; CD20 is a surface molecule expressed on B cells


What is alemtuzumab?


A humanized anti-CD52 monoclonal antibody (Campath 1H)


What are the anti-inflammatory effects of glucocorticoids?


Inhibition of cytokine gene transcription in macrophages; inhibition of cytokine secretion (IL-1, IL-6, TNF); suppression of the production and effect of T-cell cytokines; inhibition of the ability of macrophages to respond to lymphocyte-derived signals (migration inhibition factor, macrophage activation factor); suppression of prostaglandin synthesis


RENAL TRANSPLANT


What are the indications for kidney transplant?


Irreversible renal failure from: glomerulonephritis; pyelonephritis; polycystic kidney disease; malignant HTN; reflux pyelonephritis; Goodpasture syndrome; congenital renal hyperplasia; Fabry disease; Alport syndrome; renal cortical necrosis; damage from DM I


Define renal failure.


Glomerular filtration rate (GFR) < 20% to 25% normal; GFR drops to 5% to 10% of normal; uremic symptoms begin (lethargy, seizures, neuropathy, electrolyte disorders)


What is the most common reason for kidney transplant?


Diabetes (25%)


What are the 3 anastomoses of a heterotopic kidney transplant?


Renal artery to iliac artery; renal vein to iliac vein; ureter to bladder


If the choice of a left or right donor kidney is available, which one is preferred and why?


The left kidney; longer renal vein allows for an easier anastomosis


Why is the external iliac artery preferred over the internal iliac artery for vascular anastomosis during a renal transplantation?


The external iliac artery requires less dissection and there is less of a chance for anastomotic narrowing over the internal iliac artery


What might happen if accessory renal arteries are ligated in a renal allograft used for transplantation?


Renal infarcts/necrosis; ureteral necrosis; urinary fistula formation


What is the expected time period for return of normal renal function after renal transplantation?


Living related 3 to 5 days; cadaveric 7 to 15 days


What drug is used routinely by most centers for prophylaxis against urinary tract infections and Pneumocystis jiroveci (carinii)?


Trimethoprim-sulfamethoxazole


What is the most common cause of sudden cessation of urinary output in the immediate postoperative period following a renal transplant?


The presence of a blood clot in the bladder or urethral catheter; can be relieved by irrigation


How is the definitive diagnosis of a primary infection with polyomavirus (type BK) made in a patient with a kidney transplant?


Allograft biopsy to demonstrate nuclear inclusions in tubular epithelial cells and the absence of rejection or drug toxicity


What is the mainstay of treatment of posttransplant lymphoproliferative disorder (PTLD)?


Decreasing the level of immunosuppression


REJECTION AFTER RENAL TRANSPLANT


What kind of rejection results from preformed antibodies against the donor organ characterized by the transplanted kidney turning blue within minutes of revascularization?


Hyperacute rejection


When does acute cellular rejection after renal transplantation occur?


The first few weeks-months after transplantation, and occasionally years later


What is the red flag that indicated rejection following renal transplantation?


Increasing creatinine


What are the classic signs and symptoms of acute cellular rejection after renal transplantation?


Malaise, fever, oliguria, hypertension, tenderness, swelling of the allograft, elevated creatinine


When does chronic allograft nephropathy occur?


Often after years of stable function; may be accelerated in allografts that have had multiple or incompletely treated episodes of acute rejection


GRAFT AND PATIENT SURVIVAL AND COMPLICATION RATES


What is the 1-year graft survival for a living donor kidney compared to a standard criteria cadaveric kidney?


95% for a living donor kidney; 91% for a standard-criteria cadaveric kidney


What is the 5-year graft survival for a living donor kidney compared to a standard criteria cadaveric kidney?

Aug 13, 2019 | Posted by in ABDOMINAL MEDICINE | Comments Off on Transplant and Immunology
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