3.4.3 Liver Transplant Case Discussions

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 of which organ?

Answer 2

Liver

Question 3

What are the three different types of rejection?

Answer 3

Hyperacute, Acute, Chronic

Question 4

What occurs in hyperacute transplant rejection.

Answer 4

1. Pre-existing Ab’s bind onto the donors Ag’s.
2. These Ab’s allow for the activation of complement.
3. Complement leads to inflammation
4. Resulting in thrombosis

Question 5

What are the two subsets of acute transplant rejection? What cell is the primary mediator of each?

Answer 5

Early: CD8+ CTLs

Late: CD4+

Question 6

List some important characteristics of early acute vs. late acute rejection.

Answer 6

Early Acute

• Days to wks after transplant
• Early rejection involves CTLs
• CTLs react to donor APC presenting donor Ag on MHC Class I

Late Acute

• Months to years after transplant
• T helper (1) mediated (CD4+)
• T cells responding to recipient APC presenting donor Ag on MHC II

Question 7

In which organs is hyperacute rejection most common?

Answer 7

Kidney, Lung, Heart

Question 8

With transplant surgery, there is a lot of damage occurs. Descibe how that damage manifests an immune response.

Answer 8

DAMPs (Hsp70, polysaccharide fragments from heparin sulfate, HMBG1/Rage, Fibrinogen) -> Pattern Recognition Receptors (TLRs, CLRs, NODs, NLRs, RLRs) -> Innate immune system -> Inflammation, complement, leukocyte recruitment, clearance and killing, and adaptive immunity

Question 9

Differentiate between direct and indirect activation of the host immune system.

Answer 9

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

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

Question 10

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

Answer 10

Yes, this is a bit murky when it comes to exact classification.

Question 11

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

Answer 11

Steriods

Question 12

If steriods don’t work when treating acute rejection, what is the next appropriate treatment options?

Answer 12

Anti-thymocyte Globulins (bind and sequester, can lead to destruction)

Anti-CD3 (OTK)

Anti-IL2R

Question 13

Which two drugs work to directly inhibit activation of calcineurin?

Answer 13

Cyclosporine and Tacrolimus

Question 14

What is the mechanism of action of sirolimus, the cousin of tacrolimus?

Answer 14

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

Question 15

What is going on in this liver?

Answer 15

Recurrent HCV.

Note-worthy: 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 immunosuppresants like cyclophosphamide and tacrolimus, the patient’s CTLs take a major hit. The CTLs are commonly used in immune survellience and fighting off viral infections. Without CTLs, the virus has free reign.

Question 18

How do you go about treating PTLD?

Answer 18

1st, reduce immunosuppression

Ab therapy (eg. Rituximab - Anti-CD20)

Chemo

Adoptive T cell therapy

Antiviral (relatively limited)

Question 19

Info Dr. Fischer added at the end.

Answer 19

Question 20

Just some more HS since four years wasn’t enough for some of us. *Cough cough* Miles