Chapter 5 Flashcards
What continues to pose a major challenge to the long-term success of organ transplants?
Alloimmune response
How can allograft rejections be categorized?
Hyperacute (mins to hrs)
Acute (days to wks)
Chronic (mos to yrs)
What is the purpose of the innate immune system?
Detect and eliminate foreign pathogens on the basis of a broad range of molecular/cellular markers
What are examples of agents of innate immunity?
NK cells
Toll-like receptors (TLRs)
The complement cascade
What is the adaptive immune system?
Has the capacity to generate highly specific immune responses
What are the four axes of the adaptive immune system?
Specificity
Inducibility
Memory
Tolerance to self
What is the function of MHC class I?
Expressed by all nucleated cells
Presenting antigens from within the cells
Humans express HLA-A, B, and C
What is the function of MHC class II?
Typically presents antigens present in the extracellular space
Humans express HLA-DP, DQ, and DR
Comprises an alpha and a beta chain
What are members of antigen-presenting cells?
Dendritic cells (DCs)
Tissue macrophages
B cells
What is currently the mainstay of antirejection immunotherapy at the time of transplantation?
T-cell-directed immunosuppression
What genes compose the MHC?
Six genes mapped to a region of chromosome 6
How are alloantibodies detected?
Via crossmatch assays in clinical HLA laboratories at transplant centers
What organ is more resistant to antibody-mediated damage?
Liver
Where is the MHC class II expressed?
On the thymic epithelium and APCs
Describe hyperacute rejection
Occurs within minutes of graft revascularization and is the result of preformed antibodies directed against donor alloantigens
How can a hyperacute rejection be prevented?
Panel reactive antibody assay
Crossmatching
What is the most frequent form of rejection seen clinically? What is it the result of?
Acute rejection
Result of alloreactive T-cell activation via the direct and indirect pathways of antigen presentation
Over what time period does acute rejection occur?
Within a few weeks of transplantation
What is the major cause of late graft failure?
Chronic rejection
Over what time period does chronic rejection occur?
Mos to yrs after transplantation
How are organs preserved?
Hypothermia is induced by flushing the organs with 4 degrees C preservation solution and storing them on ice
Which kidney is the graft of choice in renal transplantation and why?
Left kidney because of a longer renal vein and easier access to the renal artery
When is there high acute mortality in a liver transplant?
If a liver transplant occurs for acute liver failure as opposed to chronic liver dz
When do the worst outcomes occur in a liver transplant?
With Hep C and advanced malignancy
What must occur with donors and recipients of heart transplants?
They must be ABO and size (within 20% total body weight) compatible
What is the most frequent symptom of rejection of a heart transplant?
Fatigue
What is the gold standard of dx of acute cardiac allograft rejection?
Endomyocardial biopsy
What is the MOA of steroids?
Suppress the immune system via inhibition of DNA and RNA synthesis
What is long-term administration of corticosteroids associated with?
HTN Hyperlipidemia Hyperglycemia Catarct formation Osteoporosis Psychosis Pancreatitis GI tract bleeding, ulceration and perforation Poor wound healing Growth retardation
Which calcineurin inhibitors can cause nephrotoxicity?
Cyclosporine
Tacrolimus
Which cell cycle inhibitor causes less nephrotoxicity than calcineurin inhibitors? What else could it cause?
Sirolimus
However, it causes more HTN, hepatic artery thrombosis
Also can cause hyperlipidemia, pneumonitis, acne, and rashes and can interfere with wound healing
What are some characteristics of mycophenolate mofetil?
Antimetabolite
No renal toxicity but causes bone marrow suppression
Contraindicated in pregnancy
When is azathioprine used?
In pts intolerant to MMF (mycophenolate mofetil)
Which antimetabolite is rarely used?
Methotrexate
What is the exception to methotrexate being rarely used?
Pediatric heart transplant
What are examples of anti-t lymphocyte antibodies?
Thymoglobulin
Basiliximab (Simulect)
Alemtuzumab (Campath)
Belatacept (Nulojix)
What is rituximab (Rituxan) used for?
Anti-b lymphocyte antibody
Hodgkin B-cell lymphoma
