Liver and Transplant

Question 1

What are three immune complications possible with transplant

Answer 1

Rejection, Infection, Malignancy

Question 2

What do high levels of AST and ALT relate to the function which organ?

Answer 2

Liver

Question 3

What are the different type of organ rejection?

Answer 3

• Hyperacute
• Acute Early (CD8-driven)
• Acute Late (CD-4 driven)
• Chronic

Question 4

Describe Hyperacute Rejection

Answer 4

1. Pre-existing Ab’s bind onto donor Ag’s
2. These Ab’s allow for activation of complement
3. Complement leads to inflammation
4. Result is thrombosis

Question 5

List the important characteristics of early vs. late acute rejection

Answer 5

Early Acute

• Days to weeks after transpllant
• Early rejection involves CTLs
• CTLs react to donor APC presenting donor Ag on MHC I

Late Acute

-Months to years after transplant

Th1 mediated CD4+

-T cells responding to recipient ACP presenting donor Ag on MHC II

Question 6

In which organs is hyperacute rejection most common?

Answer 6

Lung, Kidney, Heart

Question 7

With transplant surgery, these is alot of damage. Describe how that damage manifests an immune response

Answer 7

DAMPS (Hsp70, polysaccharide fragments from heparin sulfate, HMBG1/Rage, Fibrinogen) –> PPR (TLRs, CLRs, NODs, BLRs, RLRs) –> Innate immune system –> inflammation, complement, leukocyte recruitment, clearance and killing, and adaptive immunity

Question 8

Differentiate between direct and indirect activation of the host immune system

Answer 8

Direct: The donor APC presents donor Ag on MHC class I to host CD8+ Cells

Indirect: The host APC presents donor Ag on MHC class I to host CD4+ T cells

Question 9

Is it possible for acute rejection to display a mixtube of both CD4+ and CD8+ cellular infiltrate?

Answer 9

Yes, this can make classification difficult

Question 10

If you have a patient who present with both histologically and biochemically acute rejection, what is the first line treatment?

Answer 10

Steroids, the side effects suck though

Question 11

What is chronic rejection exemplified by?

Answer 11

Duct loss and less inflammation, more fibrosis

Question 12

If steroids dont work, then what?

Answer 12

Anti-thymocyte Globulins (bind and sequester, can lead to destruction) - this is basically an anti-T cell drug, it is a polyclonal antibody against numerous lymphocyte markers that will eithe inhibit or destory T-cells

Anti-CD3 (OKT3)

Anti-ILR

Question 13

Which two drugs inhibit activation of calcineurin?

Answer 13

Cyclophosphamide and Tacrolimus

Question 14

What is the mechanism of sirolimus?

Answer 14

Helps block signaling through IL-2R, thus preventing replication that is induced by IL-2, like T-cells

Question 15

What is this?

Answer 15

Recurrent HCV

-actually looks pretty good though, because there is no attack on the bilary ducts

Question 16

What does PTLD stand for? What type of infection is it most commonly associated with?

Answer 16

Post-Transplant Lymphoproliferative Disorder: reactivation or primary infection of EBV

Question 17

PTLD happens why?

Answer 17

Since we use immunosuppressant, the pateients CTLs are not able to do enough immune survellience and so virus has free raign, so do tumors

Question 18

How do you trat PTLD?

Answer 18

1. reduce immunosuppression
2. Ab therapy vs. B cells like Rituximab
3. Chemo
4. Adoptive T cell therapy
5. antibiral agents are relatively limited

Question 19

Enjoy

Question 20

Enjoy some more