Repro Topic 5 - Organ Transplant

Question 1

Define autologous transplant

Answer 1

Donor and recipient same

Question 2

Define chronic allograft nephropathy

Answer 2

• May develop after damage to the graft kidney due to acute rejection
• Progressive immunological injury to graft - more slowly compromises organ function than acute rejection
• May need another transplant

Question 3

What are the consequences of HLA mismatch in bone marrow transplants?

Answer 3

Bone marrow transplant - recipient immune system replaced with donor, can generate immune response against recipient

Question 4

How are donor organs allocated in the UK?

Answer 4

• Matched and allocated in fair, unbiased way (equity of access)
  
  • Based on clinical need, waiting time and compatibility

Question 5

How can blood group incompatibility be overcome to allow successful transplant?

Answer 5

Can be overcome prospectively by reducing antibodies through immunoadsorption, plasma exchange and immunosuppression

Question 6

Define allogenic transplant

Answer 6

Donor and recipient not genetically identical but from same species - related or unrelated

Question 7

Define syngeneic transplant

Answer 7

Donor and recipient genetically identical twins

Question 8

Where are HLA class 1 and class 2 genes expressed?

Answer 8

• Class 1 expressed on almost all cells, including platelets
• Class 2 more restricted expression - antigen-presenting cells, activated T cells, other activated/disturbed cells

Question 9

What are the consequences of blood group incompatibility in organ transplant?

Answer 9

Hyperacute rejection of organ

Question 10

What effects do donor specific antibodies have when an incompatible organ is transplanted?

Answer 10

• Activate complement
• Endothelial cell damage
• Immune cell recruitment (proinflammatory cytokines)
• Inflammation
• Platelet activation + aggregation
• Thrombosis
• Reduced blood flow, necrosis

Question 11

What is HLA sensitisation?

Answer 11

Make antibodies against non-self HLA

Question 12

Describe the criteria for transplant allocation

Answer 12

1. Paediatic (HLA match), highly sensitised
2. Paediatric (HLA match), without HLA antibodies
3. Adult patients (HLA match), highly sensitised
4. Other adult patients (HLA match)
5. All other eligible patients

Priority for 3, 4, 5 according to points scheme based on waiting time, HLA match, age, age difference between donor and recipient, location, blood group match

Question 13

Define xenogenic transplant

Answer 13

Donor and recipient from different species

Question 14

What is the function of HLA class 2?

Answer 14

• Bind peptides from extracellular and cell surface including from bacteria
• Assembled partially in endoplasmic reticulum, transported via golgi to MIIC vesicles - HLA-DM aids peptide binding
• Recognised by CD4+ T cells

Question 15

Where is the major histocompatibility complex located? What is its function?

Answer 15

Short arm of chromosome 6

Contains HLA genes - role in immune response

Question 16

Describe HLA matching for solid organ transplantation

Answer 16

• Kidneys - match HLA-A, B, avoud if donor specific antibodies
• Liver - no HLA matching done, no hyperacute reaction
• Cardiothoracic - matching important but not done due to logistics

Question 17

Describe the structure of HLA class 1

Answer 17

• Alpha 1, 2, 3 and beta2-m chains
• HLA - A, - B, - C
• Polymorphisms on exons 2 and 3

Question 18

What are the consequences of incompatible transplants in HLA sensitised individuals?

Answer 18

• Preformed alloreactive antibodies target and attack transplanted organs and blood vessels resulting in rejection of the transplanted organ
• Rejection can be immediate- hyperacute reaction - or delayed acute rejection

Question 19

List the types of allogenic donors and give examples

Answer 19

1. Living - haematopoietic stem cells, kidney, liver lobe, lung lobe
2. Deceased - kidney, liver, pancreas, heart ( + lungs), cornea etc.

• Donation after brainstem death vs after cardiac death

Question 20

How is compatibility of donor organs to recipients determined?

Answer 20

• Blood group
• Major histocompatibility complex - try to match but accept mismatch, use immunosuppression

Question 21

Describe the structue of HLA class 2

Answer 21

• Alpha 1, 2 and Beta 1, 2 chains
• HLA-DR, -DQ, -DP
• Polymorphisms in exon 2

Question 22

How does HLA matching effect organ transplantation?

Answer 22

• High diversity of HLA genes - disadvantage for transplantation as perfect match is unlikely, immunosuppression usually required
• HLA matching done for transplants, mismatch is accepted

Question 23

What is the function of HLA class 1?

Answer 23

• Bind peptides from intracellular proteins including from viruses
• Peptides transported by transporter associated with antigen processes (TAP) - on luminal side of endoplasmic reticulum, by accessory molecules e.g. tapasin
• Once MHC-peptide complex assembled - transported via golgi to cell surface, interact with CD8+ T cells at monomorphic epitote

Question 24

How can HLA sensitisation occur?

Answer 24

• Pregnancy - from father
• Blood transfusion - HLA class 1 on platelets
• Previous transplant - if wasn’t perfect match, make antibodies against
• Viral infection (cross-reactivity)

Question 25

Define direct allorecognition and alloreactivity

Answer 25

• Direct allorecognition - recipient T cells recognise non-self HLA, triggers immune response
• Alloreactivity - T cells respond vigorously to non-self HLA molecules