Immuno: Transplantation Pt.2

Question 1

Which technology is used for AB/HLA typing?

Answer 1

DNA sequencing using PCR

Question 2

At what stages of transplantation will screening for antibodies be performed?

Answer 2

• Before transplantation
• At the time of transplant (once an organ has been assigned)
• After transplantation (check for new antibody formation)

Question 3

Name and describe three assays for anti-HLA antibodies.

Answer 3

• Cytotoxic Assays: tests whether patient serum binds donor lymphocytes in the presence of complement
• Flow Cytometry: tests whether patient serum binds donor lymphocytes irrespective of complement
• Solid Phase Assays: beads containing all the possible HLA epitopes are mixed with the patient’s serum. This determines which HLA types the patient has antibodies against. Having many antibodies against different HLA epitopes suggests that the patient is highly sensitised.

Question 4

How can organ mismatch issues be overcome?

Answer 4

• Improve transplantation across tissue barriers
• More donors
• Organ exchange programmes
• Xenotransplantation and stem cell research

Question 5

What T cell pathway is the main target for immunosuppressive drugs used in transplants?

Answer 5

• The main signal is between MHC and TCR
• Downstream, there are a number of pathways that involve calcineurin which result in cell proliferation
• Once activated, T cells will release IL2 which has autocrine and paracine effects on Th2 cells
• These are all targets for immunosuppression

Corticosteroids affect numerous pathways

Question 6

Name two drugs that target TCR.

Answer 6

• Muromonab-CD3 (OKT3) - anti-CD3 antibody
• Anti-thymocyte globulin

Question 7

Name an anti-CD52 antibody

Answer 7

Alemtuzumab

Question 8

Name an anti-CD25 antibody

Answer 8

Basiliximab / Daclizumab - binds to CD25 (alpha subunit of IL-2 receptor)

Question 9

What are the main immunosuppressive targets of B-cell mediated graft rejection?

Answer 9

• B cell activation
• Secretion of antibodies by plasma cells
• Effects of antibodies on endothelium

Question 10

What is rituximab?

Answer 10

Anti-CD20 - depletes B-cells

Question 11

Give an example of a BAFF inhibitors and explain how it works.

Answer 11

Belimumab

• BAFF is required for B-cell survival
• Without BAFF, B-cells undergo apoptosis

Question 12

Name a proteasome inhibitor and describe how it works.

Answer 12

Bortezomib

• Inhibits degradition of pro-apoptosis proteins
• Eventually leads to apoptosis

Question 13

Name a complement inhibitor.

Answer 13

Eculizumab - targets C5

Question 14

Outline the components of modern transplant immunosuppression regimes.

Answer 14

Question 15

What is the managment of immunosuppressant associated

• Drug toxicity
• Viral infection
• Post-tranplant lymphoproliferative disease

Answer 15

Reduce immunosuppressant drug treats all

Post-tranplant lymphoproliferative disease may also require chemotherapy

Question 16

Briefly describe the pathophysiology of graft-versus-host-disease.

Answer 16

• During SCT, the host immune system is eradicated and replaced by autologous or allogeneic bone marrow
• In allogeneic stem cell transplant, donor lymphocytes can attack host tissues

NOTE: if there is a malignancy, the graft can kill these cells (graft-versus-leukaemia)

Question 17

How can GvHD be prevented?

Answer 17

Methotrexate with ciclosporin

Question 18

List some symptoms of GVHD.

Answer 18

• Skin - maculopapular rash (pruritic and painful)
• GI - diarrhoea/bloody stools, abdominal pain, nausea and vomiting
• Liver - jaundice, deranged LFTs

Question 19

List some opportunistic infections that are more common in transplant recipients.

Answer 19

• CMV
• BK virus
• PCP

Question 20

List some malignancies that are more common in transplant recipients.

Answer 20

• Kaposi sarcoma (HHV8)
• Lymphoproliferative disease (EBV)
• Skin cancer