1. Transplantation Immunology
Haris Saddique
MPhil Scholar
Department of Biotechnology
University of Malakand
Kpk , Pakistan

2. POINTS TO BE DISCUSSED
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Introduction
Types of grafts,
Transplantation antigens
Mechanisms of graft rejection
Tempo of Rejection
Graft versus Host Reaction (GVHR)
Prevention of rejection

3. INTRODUCTION
Transplantation:
the process of taking cells,
tissues, or organs from one individual and placing them
into a different individual or different site of the same
individual
Graft: transplanted cells, tissues, or organs.
Donor: the individual who provides the graft.
Recipient: the individual who receives the
graft. Also called the host.

4. Types of Grafts
• Autologous or autograft (self)
• e.g., BM, peripheral blood stem cells, skin, bone
• Syngeneic or isograft (identical twin)
• Allogeneic or allograft (another human except
identical twin)
• Xenogeneic or xenograft (one species to another)

6. Transplantation antigens
• Major histocompatibility antigens (MHC
molecules)
• Minor histocompatibility antigens
• Other alloantigens

7. MAJOR HISTOCOMPATIBILITY
COMPLEX (MHC)
• Is located on short arm of chromosome 6
• It includes 3 regions: class Ia (loci A, B, C) class Ib
(loci E, F, G, H), class II (loci DR, DQ, DP) and
class III
• Genes of class Ia and class II are highly
polymorphic, while those of class Ib and class III
are not
• Polymorphism means occurence of several allelles
i.e genes encoding various MHC antigens located
at the same locus

8. Map of Human MHC

9. MAJOR HISTOCOMPATIBILITY
ANTIGENS
• Histocompatibility antigens are expressed on all
nucleated cells (class I) and on APC,
B cells, monocytes/macrophages (class II)
• They are targets for rejection
• They are inherited from both parents as MHC
haplotypes and are co-dominantly expressed

10. MINOR HISTOCOMPATIBILITY
ANTIGENS
• They also participate in rejection but to lesser
degree
• Disparity of several minor antigens may result in
rejection, even when MHC antigens are
concordant between donor and recipient
• They include normal cellular constituents
• They are peptides derived from polymorphic
cellular proteins bound to MHC class I molecules

11. • Also cause grafts rejection, but slow and
weak
• Mouse H-Y antigens encoded by Y
chromosome
• HA-1 ～ HA-5 linked with non-Y chromosome

12. OTHER ALLOANTIGENS
• Human ABO blood group antigens
• Some tissue specific antigens
– Skin ＞ kidney ＞ heart ＞ pancreas ＞
liver
– VEC antigen
– SK antigen

13. Rejection
•
First Set Rejection
• Skin graft in mice 10-14 days
•
Second Set Rejection
• Skin graft in mice in 3-6 days

15. MECHANISM OF ALLOGRAFT
REJECTION
The immune responses in allogeneic
transplantation:
 T cell mediated rejection of allograft
 Antibody mediated rejection of allograft
 NK cell mediated rejection of allograft

16. T cell mediated rejection of allograft
(mechanism of cellular immunity)
1) Recognition of alloantigens
2) Activation of T cells and rejection of allograft

17. Alloantigen Recognition
• Direct presentation (Donor APC)
• Unprocessed allogeneic MHC
• Indirect presentation (Host APC)
• Processed peptide of allogeneic MHC

18. Recognition of alloantigen
• Direct recognition
------acute rejection
• Indirect recognition ------chronic rejection

19. Direct recognition of alloantigen
• Recognition of an intact MHC molecule in the
graft by T cells.

20. Indirect recognition of alloantigen
• the donor MHC molecules may be processed
and presented by recipient APCs that enter
grafts, and the processed MHC molecules are
recognized by T cells like conventional foreign
antigens.

21. Major Histocompatibility Complex (MHC)
•Class I HLA A, B, C bind to TCR on CD8 T-Cell
•Class II DR, DP, DQ bind to TCR on CD4 T-Cell

22. Activation of T cells and rejection of allograft
Host T cells may be activated by both direct
recognition and indirect recognition
• Direct pathway :
CD4+T ---- Th
CD8+T ---- CTc ---- killing graft cells
• Indirect pathway :
CD4+T ---- infiltrate the graft and recognize
donor alloantigens being displayed by host
APCs that have entered the graft ---- Th
CD8+T ---- can not directly kill the foreign cells in
the graft

24. Antibody-mediated rejection of allograft
(mechanism of humoral immunity)
Ⅰ. Complement activated by antibody involved in
transplantation rejection
Ⅱ. Antibody participate in transplantation rejection
through ADCC and opsonization
 Antibody bound to the surface of infected cell is
recognize by igG receptor on the surface of
phagocytic cell e.g NK Cells

27. NK cell mediated rejection of
allograft
• NK have receptor for allogeneic MHC proteins of
graft
• CKs secreted by activated Th cells can promote
NK activation.
• Participate in transplantation rejection through
ADCC

28. Tempo of Rejection
Solid Organ
•
Hyperacute
– Minutes to hours
– Preexisting antibodies (IgG)
Intravascular thrombosis
– Hx of blood transfusion,
transplantation or multiple
pregnancies
•
Acute Rejection
– Few days to weeks
– CD4 + CD8 T-Cells
– Humoral antibody response
– Parenchymal damage &
Inflammation
•
Chronic Rejection
– Chronic fibrosis
– Accelerated arteriosclerosis
– 6 months to yrs
– CD4, CD8, (Th2)
– Macrophages
Stem Cell
Not Applicable
10 – 30 Days
Lysis of donor stem cells
30 days – 6 months
Lysis of donor stem cells

29. Graft versus Host Reaction
(GVHR)
 When grafted tissue has mature T cells, they will
attack host tissue leading to GVHR.
 Major problem for bone marrow transplant.
 Methods to overcome GVHR:
 Treat bone marrow to deplete T cells.
 Use autologous bone marrow.
 Use umbilical cord blood

30. Prevention & Treatment
of Allograft Rejection
•
ABO Compatible
(Prevent hyperacute rejection in solid organs)
(Prevent transfusion reaction in BM/PBSC)
•
MHC allele closely matched
•
Calcineurin inhibitors
– Cyclosporine binds to Cyclophillin
– Tacrolimus (FK506) binds to FK Binding Proteins (FKBP)
– Calcineurin activates Nuclear Factor of Activated T-Cells (NFAT)
– NFAT promotes expression of IL-2
•
IMPDH Inhibitors (Inosine Monophosphate Dehydrogenase)
– Mycophenolate Mofetil (MMF)
– Inhibits guanine nucleotide synthesis
– Active metabolite is Mycophenolic acid (MPA)

31. THANKS FOR YOUR ATTENTION
&
HAVE A NICE DAY