1. Transplantation Pathology
Kristine Krafts, M.D.

2. Transplantation Outline
Introduction
Graft compatibility
Graft rejection
Types of organ transplantation

3. Transplantation Outline
Introduction

4. Definitions
Transplantation the moving of cells, tissues, and organs from one site to another
Graft the transplanted organ
Donor person from whom graft is taken
Recipient (host) person who gets the graft

5. Transplantable Things
Kidney
Pancreas
Heart
Lung
Liver
Bone marrow
Intestine
Skin
Cornea

6. Transplantation Problems
Surgical difficulties
Graft rejection
Organ shortage

7. Transplantation Outline
Introduction
Graft compatibility

8. Compatibility
Rejection recipient recognizes graft as foreign, and destroys it
Autograft within same person
Isograft between identical twins
Allograft between genetically different people
Xenograft between different species

9. Histocompatibility Histocompatible: antigenically similar
Histoincompatible: antigenically different
MHC antigens are the most important
ABO antigens are also important

10. HLA Complex Gene collection on chromosome 6
Three regions: class I, class II, class III
Class I gene products
expressed on nearly all cells
present antigen to TC cells
Class II gene products
expressed on antigen-presenting cells
present antigen to TH cells

12. MHC genes on chromosome 6 = “haplotype”♂ ♀ ♂ ♀
MHC genes on chromosome 6 = “haplotype”

13. HLA genes are inherited as sets (haplotypes)♂ ♀
parents
four possible haplotype combinations in children

14. HLA genes are polymorphic♂ ♀
A B C DR DQ DP
1 7 w
Dad’s HLA genes
2 8 w
3 44 w
Mom’s HLA genes
11 35 w

15. If HLA genes were foods…
ice cream
yum yum
pop
fruit
cookie
veggie a b
Dew
haplotypes
Vault c d

16. HLA genes are codominantly expressed

17. HLA Matching
The more matching alleles between donor and host, the better!
Matching the class II antigens is more important than matching the class I antigens.
One or two class I mismatches = no big deal
One or two class II mismatches = big deal
Mismatches in both class I and II = very big deal

18. time after transplant, months
100
number of mismatches
Class I
Class II
1 or 2
3 or 4
graft survival, % 50 3 6 12
time after transplant, months

19. Transplantation Outline
Introduction
Graft compatibility
Graft rejection

20. Graft Rejection
Any two people (except identical twins) will express some HLA proteins that are different.
Every recipient will recognize, and react against, at least some foreign antigens in the graft
Rejection is complex, with lots of killing mechanisms.

21. How does rejection happen?
T-cell-mediated rejection
Antibody-mediated rejection

22. CTL Killing

23. Antibody-Mediated Rejection
Preformed antibodies: within hours
Newly-made antibodies: days – years later

24. Clinical Types of Rejection
Hyperacute rejection
Acute rejection
Chronic rejection

25. Hyperacute Rejection Within hours Preexisting anti-donor antibodies
Rare these days

26. Acute Rejection
Starts at about 10 days
Cell-mediated

27. Chronic Rejection Months to years after transplant
Humoral and cell-mediated mechanisms
Hard to prevent
Hard to treat

28. Transplantation Outline
Introduction
Graft compatibility
Graft rejection
Types of organ transplantation

29. Kidney Transplantation
Diabetes, glomerulonephritis, congenital disorders
Most commonly transplanted organ
Problems:
host sensitization
post-transplant malignancy

30. Heart Transplantation
Cardiomyopathy, myocarditis, congenital defects, ischemic disease
Must use heart-lung machine
Problems:
organ shortage
maintaining graft before transplant
post-transplant lymphoma

31. Bone Marrow Transplantation
Leukemia, lymphoma
Find living donor (easy) that matches (hard)
Massive chemo/radiation first
Problem: GVHD

32. Graft-vs-Host Disease
Donor T cells see recipient as foreign!
Attack skin, GI, liver
Treat with immunosuppressive drugs
Or, partially deplete donor marrow of T cells

33. Graft-vs-host disease, skin lesions