Transplantation

Question 1

Acute GvHD

Answer 1

<100d post Tx.
Skin - bulluos blistering, burns-like
Liver - liver failure
Gut - inflamm, blood diarrhoea, cramps

Question 2

Chronic GvHD

Answer 2

> 100d post Tx

skin, mucous membranes, gut, liver, kidneys, eyes, joints

Question 3

Risk factors for GvHD (7)

Answer 3

age
sex of D/R (M-->F)
disease stage
viral status (cmv reactivation) 
HLA disparities
stem cell source (peripheral blood)
conditioning regime - the more immunosuppressants used the less likely GvHD is, but more likely relapse is

Question 4

Prevention of GvHD

Answer 4

HLA matching

Methotrexate and cyclosporin –> T cell depletion (but increase relapse rate)

Question 5

Rx of GvHD

Answer 5

steroids
cyclosporin
mycophenate mofetil
monoclonal abs
photopheresis
total lymphoid ablation

Question 6

Most important antigens in transplantation

Answer 6

HLA
class 2 = DR - most important. present to CD4
class 1 = A B C 
2nd most important = ABO
3rd = minor HLA

Question 7

rejection reaction where donor APC presents donor HLA to recipient T cell => cellular mediated toxicity (type IV hypersens)

Answer 7

Direct cellular mediated rejection - Acute (weeks to months)

Question 8

Symptoms of acute cellular Tx rejection

Answer 8

1. fever
2. worsening function of the allograft
3. tenderness over allograft

Question 9

pathology of acute cellular rejection on biopsy

Answer 9

increased monocytic infiltrates, graft infiltration by CD4, CD8, macrophages.

Question 10

Cause of hyperacute rejection reaction

Answer 10

mins to hours after tx
due to preformed abs - antiABO, anti-HLA
can be prevented with adequate matching and screening pre-Tx

Question 11

rejection reaction where recipient APC presents donor HLA to recipient T cell => type Iv hypersensitivity

Answer 11

Indirect cellular mediated rejection

usually chronic

Question 12

3 signals needed for t cell activation

Answer 12

TCR:APC
costim
cytokines

Question 13

pathology seen in ab-mediated acute rejection on biopsy

Answer 13

infiltrates of PMN
complement (C4) deposition
mainly in capillaries and blood vessels, vasculitis

Question 14

activation signals in acute ab-mediated rejection

Answer 14

phagocyte activation via Fc receptor

complement activation via ab-ag complexes

Question 15

antibodies for ab-mediated rejection

Answer 15

ABO-abs - naturally occuring dependent on blood type

HLA-abs - non-natural, acquired via - prev tx, pregnancy, blood tx

Question 16

Tests for preformed abs in the blood

Answer 16

complement-mediated cytotoxicity test
flow cytometry
solid phase assay

Question 17

complement-mediated cytotoxicity

Answer 17

does the recipient serum kill donor lymphocytes in the presence of complement?

Question 18

flow cytometry

Answer 18

does recipient serum bind donor lymphocytes –> fluoresce

Question 19

solid phase assay

Answer 19

does recipient serum bind donor-specific HLA (types and subtypes) –> fluoresce

Question 20

Induction agents used in transplantation (target signals 1,2 and 3)

Answer 20

1. OKT3/ATG - blocks lymphocyte activation and migration
2. anti-CD25 - binds a-chain of IL-2 receptor - inhibits t cell proliferation
3. anti-CD52 - binds cd52 found on lymphocytes and causes depletion

Question 21

baseline agents used in transplantation

Answer 21

calcineurin inhibitors - tacrolimus or cyclosporin
azathioprine/mycophenate mofetil
+/- steroids

Question 22

treatment of acute T cell mediated rejection

Answer 22

ATG/OKT3 (muromumab)

steroids

Question 23

treatment of acute ab mediated rejection

Answer 23

IVIG, plasma exchange, anti-CD20, anti-C5

Question 24

Common post Tx malignancies

Answer 24

Viral associated (x 100)
Kaposi’s sarcoma (HHV8)
Lymphoproliferative disease (EBV)
Skin Cancer (x20)
Risk of other cancers eg lung, colon also increased (x 2-3)

Question 25

common infections post Tx

Answer 25

Cytomegalovirus
BK virus - haemorrhagic cystitis
Pneumocytis carinii
Aspergillosis - increased mortality associated