Chapter 5

Question 1

What continues to pose a major challenge to the long-term success of organ transplants?

Answer 1

Alloimmune response

Question 2

How can allograft rejections be categorized?

Answer 2

Hyperacute (mins to hrs)
Acute (days to wks)
Chronic (mos to yrs)

Question 3

What is the purpose of the innate immune system?

Answer 3

Detect and eliminate foreign pathogens on the basis of a broad range of molecular/cellular markers

Question 4

What are examples of agents of innate immunity?

Answer 4

NK cells
Toll-like receptors (TLRs)
The complement cascade

Question 5

What is the adaptive immune system?

Answer 5

Has the capacity to generate highly specific immune responses

Question 6

What are the four axes of the adaptive immune system?

Answer 6

Specificity
Inducibility
Memory
Tolerance to self

Question 7

What is the function of MHC class I?

Answer 7

Expressed by all nucleated cells
Presenting antigens from within the cells
Humans express HLA-A, B, and C

Question 8

What is the function of MHC class II?

Answer 8

Typically presents antigens present in the extracellular space
Humans express HLA-DP, DQ, and DR
Comprises an alpha and a beta chain

Question 9

What are members of antigen-presenting cells?

Answer 9

Dendritic cells (DCs)
Tissue macrophages
B cells

Question 10

What is currently the mainstay of antirejection immunotherapy at the time of transplantation?

Answer 10

T-cell-directed immunosuppression

Question 11

What genes compose the MHC?

Answer 11

Six genes mapped to a region of chromosome 6

Question 12

How are alloantibodies detected?

Answer 12

Via crossmatch assays in clinical HLA laboratories at transplant centers

Question 13

What organ is more resistant to antibody-mediated damage?

Answer 13

Liver

Question 14

Where is the MHC class II expressed?

Answer 14

On the thymic epithelium and APCs

Question 15

Describe hyperacute rejection

Answer 15

Occurs within minutes of graft revascularization and is the result of preformed antibodies directed against donor alloantigens

Question 16

How can a hyperacute rejection be prevented?

Answer 16

Panel reactive antibody assay

Crossmatching

Question 17

What is the most frequent form of rejection seen clinically? What is it the result of?

Answer 17

Acute rejection

Result of alloreactive T-cell activation via the direct and indirect pathways of antigen presentation

Question 18

Over what time period does acute rejection occur?

Answer 18

Within a few weeks of transplantation

Question 19

What is the major cause of late graft failure?

Answer 19

Chronic rejection

Question 20

Over what time period does chronic rejection occur?

Answer 20

Mos to yrs after transplantation

Question 21

How are organs preserved?

Answer 21

Hypothermia is induced by flushing the organs with 4 degrees C preservation solution and storing them on ice

Question 22

Which kidney is the graft of choice in renal transplantation and why?

Answer 22

Left kidney because of a longer renal vein and easier access to the renal artery

Question 23

When is there high acute mortality in a liver transplant?

Answer 23

If a liver transplant occurs for acute liver failure as opposed to chronic liver dz

Question 24

When do the worst outcomes occur in a liver transplant?

Answer 24

With Hep C and advanced malignancy

Question 25

What must occur with donors and recipients of heart transplants?

Answer 25

They must be ABO and size (within 20% total body weight) compatible

Question 26

What is the most frequent symptom of rejection of a heart transplant?

Answer 26

Fatigue

Question 27

What is the gold standard of dx of acute cardiac allograft rejection?

Answer 27

Endomyocardial biopsy

Question 28

What is the MOA of steroids?

Answer 28

Suppress the immune system via inhibition of DNA and RNA synthesis

Question 29

What is long-term administration of corticosteroids associated with?

Answer 29

``` HTN Hyperlipidemia Hyperglycemia Catarct formation Osteoporosis Psychosis Pancreatitis GI tract bleeding, ulceration and perforation Poor wound healing Growth retardation ```

Question 30

Which calcineurin inhibitors can cause nephrotoxicity?

Answer 30

Cyclosporine | Tacrolimus

Question 31

Which cell cycle inhibitor causes less nephrotoxicity than calcineurin inhibitors? What else could it cause?

Answer 31

Sirolimus However, it causes more HTN, hepatic artery thrombosis Also can cause hyperlipidemia, pneumonitis, acne, and rashes and can interfere with wound healing

Question 32

What are some characteristics of mycophenolate mofetil?

Answer 32

Antimetabolite No renal toxicity but causes bone marrow suppression Contraindicated in pregnancy

Question 33

When is azathioprine used?

Answer 33

In pts intolerant to MMF (mycophenolate mofetil)

Question 34

Which antimetabolite is rarely used?

Answer 34

Methotrexate

Question 35

What is the exception to methotrexate being rarely used?

Answer 35

Pediatric heart transplant

Question 36

What are examples of anti-t lymphocyte antibodies?

Answer 36

Thymoglobulin Basiliximab (Simulect) Alemtuzumab (Campath) Belatacept (Nulojix)

Question 37

What is rituximab (Rituxan) used for?

Answer 37

Anti-b lymphocyte antibody | Hodgkin B-cell lymphoma