basic immunology of transplantation, principles of donor selection, matching and organ donation

1. PRINCIPLES OF
TRANSPLANTATION SURGERY
PART 1
Dr Winston Makanga, M.B.Ch.B, M.MEd (Surg)
Consultant General and Laparoscopic Surgeon

2. Objectives of the lecture
• Definition of transplantation and related terms
• Indications of transplantation
• Types of transplants
• Immunological basis of graft rejection
• Strategies of minimizing rejection

3. Definitions
• Organ transplantation: A surgical procedure in which a failing organ is
replaced by a functioning one
• Graft types
• Allograft: organ/tissue from an individual to another
• Autograft: same individual
• Isograft: identical twins
• Xenograft: different species
• Location
• Orthotopic transplantation: same anatomical site
• Heterotopic: different anatomical site
• Alloantigens: natural antigens found on human organs
• Alloantibodies: antibodies formed against alloantigens

4. Indications of transplantation
• End organ failure
• Kidney:Diabetes, Glomerulonephritis, Pyelonephritis, Polycystic kidney
disease, Obstructive uropathy, Hypertensive nephrosclerosis.
• Liver: Cirrhosis, fulminant hepatitis
• Pancrease: chronic pancreatitis
• Heart: severe CCF not manageable by meds
• Malignancy - liver
• Massive tissue/organ necrosis - intestines

5. Common organ transplants
• Kidney
• Liver
• Heart
• Lungs
• Pancreas
• Intestines
• ?Bone marrow

6. Immunology of transplantation
• Histocompatibility: having the same, or sufficiently similar, alleles of a
set of genes called Major histocompatibility complex (MHC)
HLA/MHC class 1 – A, B, C,
HLA/MHC class 2 - Dp, Dq, Dr
MHC code for surface tissue identifying allo-antigens
called human leukocyte antigens (HLA)

7. Natural tissue surveillance and reaction to graft
• T cells do routine scouting ‘sniffing’ for foreign antigens
• T cells using TCR bind to surface HLA antigens found on:
• Class 1 – all nucleated cells
• Class 2 - APC cells: Dendritic cells, macrophages, Langerhans cells and B cells
• T cell activation ONLY occurs when there is a second signal from an
APC

8. Rejection types
• Hyperacute – immediate
• Antibody mediated
• Usually pre-existing antibodies
• Acute – upto 6 months
• Chronic – years

9. Minimizing rejection
• Reduce possibility of graft recognition as foreign
• Suppress immune response against graft

10. Review
• Definition of transplantation and related terms
• Indications of transplantation
• Types of transplants
• Immunological basis of transplantation/rejection
• Strategies of minimizing rejection

11. PRINCIPLES OF
TRANSPLANTATION SURGERY
PART 2

12. Objectives of the lecture
• Tissue matching
• Principles of immune suppression therapy
• Complications of transplantation
• Organ donation and preservation

13. Tissue matching
• ABO compatibility is mandatory
• HLA typing with close focus on HLA A, B and Dr (highest risk of
rejection if mismatched)
• This is done by isolating DNA and PCR to amplify the MHC A, B, Dr
• Each person has 3 sets from each parent (total 6)
• Typing: Donor pA pB pDr mA mB mDr
Recipient pA pB pDr mA mB mDr
• Only 25% siblings get a 6/6 match
• A 4/6 match is adequate for transplantation
• Cross matching* (recipient serum against donors leukocytes)

15. Principles of immune suppression therapy
• To stop the process of T cell activation
• Stages of T cell activation that can be stopped
1. IL 2 transcription (calcineurin inhibition)
2. Lymphocyte proliferation
3. Second signaling
4. IL 2 receptor inhibition
• Weigh benefit vs adverse effects
• Infection
• Malignancy
• Cost and availability
• Combination therapy across the classes
• Main goal is to prevent acute/subacute rejection

16. Mechanism of action of IST

17. Complications of transplantation
• Rejection
• Organ failure
• Infection
• Malignancy
• Hypertension
• Hypercholesterolemia
• Graft vs Host Disease
• Mainly in organs that contain lots of lymphocytes
• Presents as a reaction to skin and may be a full blown systemic disease

18. Organ donation and preservation
• Types of donors
1. Living donor
2. Donor after brain death (DBD)
3. Donor after circulatory death (DCD)
• Preservation of donated organs
1. In situ flushing and cold perfusion in DCD
2. Minimize warm ischemia time in DBD
3. Rapid transfer of organ from donor to recipient in LD
• Preservation Solutions used: EuroCollins, Univ of Wisconsin, HTK,
Celsior – they cool, limit swelling, acidosis & electrolyte shift

19. Review
• Tissue matching
• Principles of immune suppression therapy
• Complications of transplantation
• Organ donation and preservation

20. Thank you