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Flashcards in Transplant Surgical Recall Deck (46)
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1
Q

Define autograft.

A

same individual is both donor and recipient

2
Q

Define isograft.

A

donor and recipient are genetically identical (identical twins)

3
Q

Define allograft.

A

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

4
Q

Define xenograft.

A

donor and recipent are of different species.

5
Q

Define orthotopic.

A

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

6
Q

Define heterotopic.

A

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

7
Q

Define paratopic.

A

donor organ is placed close to orginal organ.

8
Q

Define chimerism.

A

sharing cells between the graft and donor.

9
Q

What are histocompatibilty antigens?

A

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

10
Q

Why are histocomatibity antigens important?

A

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

11
Q

Which cells have class I antigens?

A

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

12
Q

Which cells have class II antigens?

A

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

13
Q

What are the gene products of MHC called in humans?

A

HLA (human leukocyte antigens)

14
Q

What is the location of the MHC complex?

A

short arm of chromosome 6

15
Q

What is a haplotype?

A

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

16
Q

Does HLA matching matter for organ transplantation?

A

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.

17
Q

What is the function of Tcells?

A

cell mediated immunity\n\nrejection

18
Q

What are the types of Tcells?

A

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

19
Q

What is the function of Bcells?

A

humoral immunity

20
Q

What is the cell type that produces antibodies?

A

Bcells differentiate into plasma cells

21
Q

What is a macrophage?

A

a monocyte in parechymal tissue

22
Q

What is the function of macrophages?

A

process foreign protein and present it to lymphocytes

23
Q

Descibe the events leading to antibody production/

A

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

24
Q

Who needs to be immunosuppressed?

A

all recipients (except autograft and isograft)

25
Q

What is the most commonly used corticosteroid for transplants?

A

prednisone

26
Q

How does prednisone function?

A

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

27
Q

What is the toxicity associated with prednisone?

A

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

28
Q

What is the MOA of azothioprine (imuran)?

A

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

29
Q

What is the toxicity associated with azathioprine?

A

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

30
Q

When should a lower dose of AZA be administered?

A

when WNC is less than 4

31
Q

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

A

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

32
Q

What is the function of cyclosporine (CSA)?

A

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

33
Q

What is the toxicity associated with cyclosporine (CSA)?

A

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)

34
Q

What is the toxicity associated with ATGAM?

A

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

35
Q

How does OKT3 work?

A

MONOclonal antibody that binds CD3 receptor on Tcells

36
Q

What is a major problem with multiple doses of OKT3?

A

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

37
Q

What are basiliximab and daclizumab?

A

anti–CD25 monoclonal antibodies

38
Q

What is tacromilus also known as?

A

Progaf (FK506)

39
Q

How does tacromilus work?

A

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

40
Q

What is the potency of tacromilus compared CSA?

A

100 times more potent than CSA

41
Q

What are the side effects of tacromilus?

A

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

42
Q

What is sirolimus also known as?

A

rapamycin, rapamune

43
Q

How does sirolimus work?

A

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

44
Q

What is the toxicity of sirolimus?

A

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

45
Q

What is mycophenolate mofetil (mmf) also known as?

A

CellCept

46
Q

How does MMF (mycophenylate mofetil) work?

A

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