VI - Transplant

Question 1

HLA Matching
What does HLA stand for?
What are HLAs and where are they found?
Which cells express class I?
Which cells also express class II?
How many HLA?
How does this relate in families?

Answer 1

Human Leukocyte Antigen.
They are proteins located on the surface of WBCs & other tissues in the body.
All nucleated cells express class I (HLA-A,B,C).
Specialised antigen presenting cells also express class II - (HLA-DR,DQ,DP).
There are 12 HLA on each cell - 6 class I and 6 class II.
If two children inherit the exact same HLA from their parents, they are said to be an identical match. You have a 25% chance of being an identical match to your siblings.

Question 2

HLA in relations to transplant rejection.
What do you do here?
Hierarchy of importance of HLA?
How is this measured in relation to graft survival?
how is crossmatching done?

Answer 2

Try and maximise the similarity between recipient and donor HLA.
Hierarchy: HLA-DR» HLA-B&raquo_space; HLA-A.
Difference between donor and recipient is expressed as number of mismatches as HLA-A+B+DR.
The crossmatch is performed by mixing a small amount of the PATIENT’S SERUM with a small amount of the DONORS WHITE CELLS.
A positive crossmatch is a strong indication against transplantation.

Question 3

HLA matching in organ transplantation.

Give examples of organs where HLA matching is used to allocate donor and examples where it isn’t.

Answer 3

HLA is used: stem cell & kidney.

HLA isn’t used: lung, heart & liver.

Question 4

Briefly describe the pathophysiology of T cells recognising the transplant.

Answer 4

Antigen presenting cell recognises foreign protein and presents it to T lymphocyte. 
T cell is activated:
- Cytokines are produced
- Provide help to activate CD8+ T cells
- Recruit phagocytic cells

Question 5

Outline the four steps of acute cellular rejection.

Answer 5

1. Recognition of donor antigens by CD4+ T cells - activated CD4+ cells; produces cytokines; type IV hypersensitivity response.
2. Activation of CD8+ T cells - CD8+ T cells are cytotoxic and kill target cells.
3. Mobilisation of phagocytes - activated CD4+ cells recruit macrophages and neutrophils –> phagocytosis.
4. Activation of B cells - produce antibody against graft antigens.

Question 6

Symptoms of deteriorating graft function:
Kidney?
Liver?
Lung?

Answer 6

Pain and tenderness over graft; fever.
Kidney - rise in creatinine; fluid retention; hypertension.
Liver - rise in LFTs, coagulopathy.
Lung - breathlessness, pulmonary infiltrate.

Question 7

Summarise the four types of transplant rejection:
Name
Time
Pathology
Mechanism 
Treatment

Answer 7

Hyperacute rejection - minutes-hours; thrombosis & necrosis, type II hypersensitivity; preformed antibody and complement fixation; no treatment.
Acute cellular rejection - 5-30 days; cellular infiltration, type IV hypersensitivity; CD4 & CD8 T cells; immunosuppression.
Acute vascular rejection - 5-30 days; vasculitis & type II hypersensitivity; De novo antibody 7 complement fixation; treatment - immunosuppression +++
Chronic allograft failure - >30 days; fibrosis, scarring; immune & non immune mechanisms; treatment - maximise drug toxicity, hypertension, hyperlipidaemia.

Question 8

What are the common symptoms and side effects of immunosuppressive agents?

Answer 8

Infection
Malignancy
Atherosclerosis
Ciclosporin associated gingival hypertrophy
Facial hair