Transplant Surgical Recall

Question 1

Define autograft.

Answer 1

same individual is both donor and recipient

Question 2

Define isograft.

Answer 2

donor and recipient are genetically identical (identical twins)

Question 3

Define allograft.

Answer 3

donor and recipent are genetically dissimilar, but of the same species.

Question 4

Define xenograft.

Answer 4

donor and recipent are of different species.

Question 5

Define orthotopic.

Answer 5

Donor organ is placed in normal anatomic position (liver, heart)

Question 6

Define heterotopic.

Answer 6

donor organ is placed in different site than the normal anatomic position (kidney, pancreas)

Question 7

Define paratopic.

Answer 7

donor organ is placed close to orginal organ.

Question 8

Define chimerism.

Answer 8

sharing cells between the graft and donor.

Question 9

What are histocompatibilty antigens?

Answer 9

dinstict (genetically inherited) cell surface proteins of the human leukocyte antigen (HLA) system

Question 10

Why are histocomatibity antigens important?

Answer 10

They are targets (class I antigens) and initiators (class II antigens) of immune response to donor tissue (i.e., distinguishing self from nonself)

Question 11

Which cells have class I antigens?

Answer 11

all nucleated cells (think: class 1 = all cells = “one for all”

Question 12

Which cells have class II antigens?

Answer 12

macrophages\nmonocyes\nB cells\nactivated Tcells\nendothelial cells

Question 13

What are the gene products of MHC called in humans?

Answer 13

HLA (human leukocyte antigens)

Question 14

What is the location of the MHC complex?

Answer 14

short arm of chromosome 6

Question 15

What is a haplotype?

Answer 15

the combinantion of HLA genes on a chromosome inherited from one parent\n\nThus two siblings have a 25% changce of being haploidentical

Question 16

Does HLA matching matter for organ transplantation?

Answer 16

With recent improvements in immunosuppression (i.e. cyclosprine) the effect is largey obscured, but it still does matter. \n\nThe most important ones to match to improve renal allograft survival are HLA–B and HLA–DR.

Question 17

What is the function of Tcells?

Answer 17

cell mediated immunity\n\nrejection

Question 18

What are the types of Tcells?

Answer 18

Th (CD4): helper T – help B cells become plasma cells\n\nTs (CD8): suppressor T – regulate immune response\n\nTc (CD8): cytotoxic T – kill cell by direct contact

Question 19

What is the function of Bcells?

Answer 19

humoral immunity

Question 20

What is the cell type that produces antibodies?

Answer 20

Bcells differentiate into plasma cells

Question 21

What is a macrophage?

Answer 21

a monocyte in parechymal tissue

Question 22

What is the function of macrophages?

Answer 22

process foreign protein and present it to lymphocytes

Question 23

Descibe the events leading to antibody production/

Answer 23

1)macrophage engulfs antigen and presents it to Th cells; the macrophage produces IL–1\n\n2) The Th cells then produce IL–2, and the Th cells proliferate\n\n3) The Th cells then activate (via IL–4) B cells that differentiate into plasma cells, which produce antibodies against the antigen presented

Question 24

Who needs to be immunosuppressed?

Answer 24

all recipients (except autograft and isograft)

Question 25

What is the most commonly used corticosteroid for transplants?

Answer 25

prednisone

Question 26

How does prednisone function?

Answer 26

primarily blocks production of IL–1 by macrophage and stabilizes lysosomal membrane of macrophage

Question 27

What is the toxicity associated with prednisone?

Answer 27

cushingoid alopecia, striae, HTN, diabetes, pancreatitis, ulcer disease, osteomalacia, aseptic necrosis (esp of the femoral head)

Question 28

What is the MOA of azothioprine (imuran)?

Answer 28

prodrug that is cleaved into mercaptopurine; inhibits the synthesis of DNA and RNA, leading to decreased cellular (T/B cells) production

Question 29

What is the toxicity associated with azathioprine?

Answer 29

toxic to bone marrow (leukopenia + thrombocytopenia), hepatotoxic, associated with pancreatitis

Question 30

When should a lower dose of AZA be administered?

Answer 30

when WNC is less than 4

Question 31

What is the drug interaction associated with azathioprine (imuran)?

Answer 31

decrease the dose if the patient is also on ALLOPURINOL\n\nbecause allopurinol inhibits xanthine oxidase, which is necessary for the breakdown of azathioprine

Question 32

What is the function of cyclosporine (CSA)?

Answer 32

Calcineurin inhibitor inhibits the production of IL–2 by Th cells

Question 33

What is the toxicity associated with cyclosporine (CSA)?

Answer 33

Toxicity includes the 1 H's:\n1) Hepatitis\n2) Hypertrichosis\n3) gingival Hyperplasia\n4) Hyperlipidemia (worse than FK)\n5) Hyperglycemia\n6) Hypertension (worse than (FK)\n7) HUS\n8) Hyperkalemia\n9) Hypercalcemia\n10) Hypomagnesemia\n11) Hyperuricemia\n\nand 3 N's:\n1) Nephrotoxicity\n2) Neurotoxicity (headache, tremor)\n3) Neoplasia (lymphoma, KS, squamous cell skin cancer)

Question 34

What is the toxicity associated with ATGAM?

Answer 34

thrombocytopenia\nleukopenia\nserum sickness\nrigors\nfever\nanaphylaxis\nincreased risk of viral infection\narthralgia

Question 35

How does OKT3 work?

Answer 35

MONOclonal antibody that binds CD3 receptor on Tcells

Question 36

What is a major problem with multiple doses of OKT3?

Answer 36

blocking antibodies develop and OKT3 is less effective each time it is used

Question 37

What are basiliximab and daclizumab?

Answer 37

anti–CD25 monoclonal antibodies

Question 38

What is tacromilus also known as?

Answer 38

Progaf (FK506)

Question 39

How does tacromilus work?

Answer 39

similar to CSA – "calcineurin inhibitor" blocks IL–2 receptor expression, inhibits Tcells

Question 40

What is the potency of tacromilus compared CSA?

Answer 40

100 times more potent than CSA

Question 41

What are the side effects of tacromilus?

Answer 41

nephrotoxicity and CNS toxicity (tremor, seizure, parasthesia, coma) , hyperkalemia, alopecia, diabetes

Question 42

What is sirolimus also known as?

Answer 42

rapamycin, rapamune

Question 43

How does sirolimus work?

Answer 43

Like CSA and tacromilus, but it does not inhibit calcineurin, rahter it blocks Tcell signalling

Question 44

What is the toxicity of sirolimus?

Answer 44

hypertriglyceridemia\nthrombocytopenia\nwound/healing problems\nanemia\noral ulcers

Question 45

What is mycophenolate mofetil (mmf) also known as?

Answer 45

CellCept

Question 46

How does MMF (mycophenylate mofetil) work?

Answer 46

inhibitor of insosine monophosphate dehydrogenase (required for de novo purine synthesis which expanding T and B cells depend on)\n\nalso inhibits adhesion molecules and antibody production