Transplantation involves transferring living cells, tissues, or organs from one part of the body to another or from one individual to another. Major histocompatibility complex (MHC) genes encode cell surface proteins that present antigens and are involved in the body's recognition of self vs. non-self. Matching the MHC between donor and recipient reduces the risk of rejection. The immune system normally rejects transplanted tissues that are identified as foreign based on non-matching MHC proteins. Current clinical strategies aim to block this rejection response through immunosuppressive drugs.

1. Transplantation and
immunity
Shanmugham karthick raja
225-B

2. Transplantation
 Graft or
Transplant:
Transfer of living
cells, tissues and
organs from one
part of the body to
another or from
one individual to
another.

3. Nobel Prize in Physiology or
Medicine 1980
• George D. Snell (1/3), Jean Dausset (1/3)
• Discoveries concerning genetically
determined structures on the cell surface
that regulate immunological reactions
– H-genes (histocompatibility genes), H-2 gene
– Human transplantation antigens (HLA) ----MHC
Dr.T
.V.Rao MD
Great events in history of transplantation

4. Dr.T
.V.Rao MD
Definition of Transplantation
 Implantation of “non-self” tissue into the
body
 The process of taking cells, tissues, or
organs called a graft (transplant), from
one part or individual and placing them
into another (usually different individual).
 donor : the individual who provides the
graft.
 recipient or host: the individual who
receives the graft.

5. May take place between:
 different parts of the same
organism (auto grafting)
different organisms of the
same species (allografting)
 different species
(xenografting)
Methods of Transplantation:

6. Dr.T
.V.Rao MD
Classification Based on
Genetics
 Genetic basis is naming different types of
grafts
 Self to Self - Auto graft
 One individual to another – Isograft
(Identical twins) both are genetically similar
 Grafts between two genetically non
identical members of the same species are
called as allograft.

7. Dr.T
.V.Rao MD
Other names in Terminology
 Can be stored or fresh
 Transplants may be Living or Dead
 Live grafts – Kidney, Hear, also called as
Vital grafts.
 Non living – Bone, Artery
 Static or structural grafts.

8. Dr.T
.V.Rao MD
Classification of Transplants
 Based on nature of organs - Kidney, Liver,
Heart, Bone marrow, Skin
 On basis of Anatomical site – Orthotropic,
 Heterotypic
 Orthotropic – Skin graft
 Heterotypic graft 0n abnormal site eg
Thyroid gland in subcutaneous region

9. Applications of allografting
transplantation
Dr.T
.V.Rao MD

10. Dr.T
.V.Rao MD
How Grafts are accepted or
rejected.
• AA + BB
• F1 hybrid
• AB
• AB can accept graft from both AA or BB
•
• But AA or BB cannot accept the Graft from AB
•

11. Dr.T
.V.Rao MD

12. Classification of Renal
Transplantation
• Auto-RT
Cadaveric
• Allograft RT Living related
Living Donor
Living unrelated
• Xenograft RT (In experimental)
Dr.T
.V.Rao MD

13. Dr.T
.V.Rao MD
Transplants from Male to Female
• Male tissues contain xy
• When male tissue with xy grafted to female (
xx ) as females don't contain y gene
• The grafts may not be accepted
• However grafts done from female to male are
accepted.
• The Phenomenon is called as unilateral sex
linked Histocompatability is known as
EICHWALD SILMSER EFFECT.

14. Dr.T
.V.Rao MD
Transplants and the immune
system
• Discrimination between self/ nonself
• This is not good for transplants
• At first the only possible transplants
were blood transfusions
•Otherwise the grafts were disastrous
Why are blood transfusions tolerated?

15. Dr.T
.V.Rao MD
MAJOR CONCEPTS IN TRANSPLANT
IMMUNOLOGY
• How does the immune system deal with a transplant, i.e.
What are the mechanisms of rejection?
• What are the current clinical strategies to block rejection?
• What are the new and future strategies to promote
specific immune tolerance?
• What is the role of xenotransplantation?
• What is graft versus host disease?

16. Transplantation antigens
Major Histocompatibility Complex (MHC):
– gene complex whose alleles encode
polymorphic cell surface glycoproteins involved
in antigen recognition and presentation
– MHC-matching between transplant donor and
recipient greatly reduces likelihood of rejection
– nomenclature
• HLA: human leukocyte antigen
• SLA: porcine leukocyte antigen
• H-2: mouse MHC
• RT1: rat MHC

17. Transplantation antigens
Histocompatibility Complex (MHC):
–Class I antigens: constitutively expressed
on surface of most cells
–Class II antigens: expressed on cells of
lymphoid system
–Expression of MHC molecules can be
unregulated by ischemia, etc.
–nomenclature
• HLA (human) class I: A, B, C; class II: DR,
DQ
• H-2 (mouse) class I: K, D, L; class II: IA, IE

18. Dr.T
.V.Rao MD
Factors favoring Allograft Survival
• Blood group compatibility
• HLA compatibility
• HLA typing and Tissue
matching
• HLA typing identifies the
HLA antigens expressed on
the surface of leukocytes.

19. Dr.T
.V.Rao MD
Histocompatability Antigens
⚫ Immune response against
transplants depends on the
presence in the grafted tissue of
antigens that are absent in
recipient and hence recognized as
foreign

20. HLA system
Dr.T
.V.Rao MD

21. Identifying MHC polymorphisms
(‘tissue typing’)
• Formerly determined by antibodies
against MHC molecules
 HLA typing
 MLR
• Now by DNA testing: allele-specific
PCR, sequencing

22. Dr.T
.V.Rao MD
Tissue typing
• Microcytotoxicity assay
– Known antibody to WBCs of donor / recipient
– Complement mediated lysis if Ab present on cell
surface
• Mixed lymphocyte culture (MLC)
– Irradiated donor lymphocytes (stimulants)
– Incubated with recipient lymphocytes
• Flow cytometry cross typing
• DNA analysis
Genomic typing (very precise, many subtipes)

23. Dr.T
.V.Rao MD
Clinical phases of rejection
1. Hyperacute rejection (minutes to hours)
• Preexisting antibodies to donor HLA antigens
• Complement activation, macrophages
2. Accelerated rejection
3. Acute rejection (around 10 days to 30 days)
• Cellular mechanism (CD4, CD8, NK, Macrophages)
4. Chronic rejection (months to years !!)
• Mixed humoral and cellular mechanism
• CHRONIC REJECTION IS STILL HARD TO MANAGE !

24. Dr.T
.V.Rao MD
Control of Transplant Immunology
•
Transplantation immunity is
predominately by cell mediated
immunity
First response is mediated by T
lymphocytes
Humoral antibody are also
produced during Allograft
Rejection

25. Cellular and Molecular
Understandings
•Associated with graft rejections and immunosuppressive therapies
•Rejection has not been eliminated only reduced
 Hyperacute rejection
 Acute rejection
 Chronic rejection
Dr.T
.V.Rao MD