Transplant Rejection and Immunosuppressants

Question 1

what kind of HSN (so what is causing) causes hyperacute transplant rejection; timeframe?

Answer 1

Type II (antibody mediated!!)--> preformed anti-donor Abs attack graft vessels = ischemia and necrosis
* w/in minutes

Question 2

what type of HSN causes Acute transplant rejection; timeframe

Answer 2

Type IV–> cytotoxic T cells react against foreign MHC I

*occurs weeks later, usually within 3 mo

Question 3

Cause of chronic transplant rejection; timeframe

Answer 3

Months to years–> MHC I on donor tissues is perceived by host CTL as being a self- MHC I presenting foreign antigen when it isnt = obliterative vascular fibrosis and fibrosis of graft tissue

Question 4

what two things mediate chronic transplant rejection

Answer 4

Abs AND T-cell

Question 5

what type of transplant rejection is irreversible? reversible?

Answer 5

1. Chronic is irreversible

2. Acute is irreversible with immunosuppresants

Question 6

What causes graft vs host dz

Answer 6

Grafted T cells proliferate in the host and start reacting against all tissues (since it recognizes everything in host as foreign) –> severe organ dysfunction

T-cells causing, so is a Type IV hsn rxn

Question 7

what two transplant can lead to GVH dz

Answer 7

1. Bone marrow transplant
2. Liver transplant

*both organs rich in lymphocytes

Question 8

4 symptoms of GVH

Answer 8

1. maculopapular rash (neck, shoulders, ears, palms)
2. Hepatosplenomegaly
3. hemolysis/ jaundice
4. G.I. sx (N/V abdominal pain, diarrhea)

Question 9

binds to cyclophilin and inhibits calcineurin

Answer 9

Cyclosporine

Question 10

AE of cyclosporine

Answer 10

1. nephrotoxicity –> due to vasoconstriction of afferent and efferent arterioles in kidney; this also leads to HTN

Question 11

binds to FK-binding protein to inhibit calcineurin

Answer 11

Tacrolimus (FK-506)

Question 12

AE of tacrolimus

Answer 12

like cyclosporine, can cause nephrotoxicity and HTN

Question 13

what other two AEs do tacrolimus and cyclosporine share

Answer 13

1. gingival hyperplasia

2. hirsutism

Question 14

function of calcinuerin, why is blocking it helpful

Answer 14

transcription factor for IL-2–> no IL-2 = impaired T-cell proliferation and differentiation

Question 15

binds FKBP-12 and inhibits mTOR

Answer 15

Sirolimus (rapamycin)

Question 16

prodrug for 6-mercaptopurine

Answer 16

Azathioprine

Question 17

interferes with metabolism and synthesis of nucleic acids

Answer 17

Azathioprine

Question 18

must be avoided when taking allopurinol

Answer 18

Azathioprine (6-mercapturine is metabolized by xanthine oxidase, so inhibiting with allopurinol is a dumb idea)

Question 19

AE of azathiprine

Answer 19

Bone marrow suppression–> esp when taking allopurinol at some time

Question 20

inhibits IMP-dehydrogenase–> preventing synthesis of guanine

Answer 20

Mycophenolate

Question 21

binds to CD25 (IL-2 receptor)

Answer 21

Daclizumab

Question 22

interferes with TNF-alpha

Answer 22

Thalidomide

Question 23

3 drugs used for lupus nephritis (2 are of label, so mainly know on-label one)

Answer 23

1. Azathioprine
2. Cyclosporine
3. Mycophenolate

Question 24

TNF-alpha mabs (2) used mainly for seronegative spondyloarthropathies and sometime for RA

Answer 24

1. inflixumab

2. adalibumab

Question 25

mAb against glycoprotein IIb/IIIa

Answer 25

Abcixumab–> used to prevent cardiac ishemia in unstable angina (prevents platelet interactions)

Question 26

mAb against HER2 used in HER2+ breast CA

Answer 26

Trastuzumab

Question 27

mAb against CD20, used for B-cell non-Hodgkins

Answer 27

Rituxumab

Question 28

mAb to IgE

Answer 28

Omalizumab