TRANSPLANTATION IMMUNOLOGY

1. Transplantation
immunology
Submitted By-
Ashutosh Sharma
Roll no. 11081
M.Sc. biotechnology
Submitted to
Dr. Menu Goyal
Assistant professor
Central university of Haryana

2. Content
• Introduction and major events
• Laws of transplantation
• Basis of Graft rejection
• Immunosuppressive therapy
• Immune tolerance to allograft
• Clinical transplantation

3. Introduction
• Transplantation is the act of transferring cells,
tissues, or organs from one site to another.
• Implantation of non-self tissues into the body.
• Donor is from which the graft is taken and recipient
is to whom graft is implanted.

4. Major Events
• The first successful identical twin transplant of a
human kidney was performed by Joseph E. Murray
in 1954 in Boston.
• The first successful liver transplant by Dr. Thomas E.
Starzl in 1967.
• The first heart transplantation by Christian Barnard
in 1967.
• The first successful bone marrow transplant by E.
Donnall Thomas in 1968.

5. Laws of transplantation
• Transplantation within inbread strains will succeed.
• Transplantation between inbread strains will fail.
• Transplants from a member of an inbread parental
strain to an F1 offspring will succeed but those in
the reverse direction will fail.

6. Continued...
• Transplants from F2 and all subsequent generations
to F1 animals will succeed.
• Transplants from inbread parental strain to F2
generation will usually, but not always,fail.

7. Basis of graft rejection

8. Types of graft
• Autograft:is self tissue transfer from one body part
to another.
• Isograft:is tissue transfer between genetically
identical individuals.
• Allograft:is tissue transfer between genetically
different members of same species.
• Xenograft:is tissue transfer between different
species.

9. Graft
acceptance and
rejection
(a) acceptance of an allograft
occurred within 12-14 days
(b)first-set of allograft rejection
begin within 7-10 days and
completed by 10-14days
(c) second-set of rejection begin
with 3-4 days, with full rejection
by 5-6 days.

10. Role of T-cell
• In 1950s, Avrion Mitchison showed in adaptive
transfer experiment that lymphocytes , but not
serum antibody could transfer allograft immunity.
• In other studies, T-cells derived from an allograft-
primed mouse were shown to transfer second set
allograft rejection to an unprimed genetically
identical recipient , as long as that recipient was
grafted with same allogeneic tissue.

12. • Analysis of T-cell subpopulations involved in allograft
rejection has implicated both CD4+ and CD8+
population.
• Mice were injected with monoclonal antibodies to
deplete one or both T-cell and rate of rejection was
measured.

14. MHC
• MHC(major histocompatibility complex) is a tightly
linked cluster of genes that are inherited as a
complete set, called haplotype.
• The organisation of MHC is called H-2 in mice and
HLA(human leucocyte antigen) in humans.
• Class I MHC
• Class II MHC
• Minor histocompatibility complex

15. Role of RBC and MHC antigens
• Differences in the blood group and major
histocompatibility antigens are responsible for the
intense graft-rejection.
• Blood group antigens are expressed on RBCs,
epithelial cells, endothelial cells.
• HLA typing is performed majorly by two methods:
1.Microcytoxicity test
2.MLR(mixed-lymphocyte reactions)

18. Cell mediated Graft rejection
• Gtaft rejection is caused principally by cell
mediated immune response to alloantigens
(primarily MHC molecules) expressed on cells of
the graft.
• The process is divided into 02 stages:
• Sensitization stage
• Effector stage

19. Sensitization stage
• CD4+ and CD8+ T-cell recognise alloantigens and
proliferate in response.
• Minor histocompatibility antigens are weak, but
sometimes combined effects can vigorous.
• Major histocompatibility antigens recognise both
MHC molecule and protein bound to it.

20. Effector stage
• Immune Destruction of graft takes place.
• A variety of effector mechanism participate in
allograft rejection. The most common are cell
mediated reactions involving DTH and CTL
mediated cytotoxicity.
• Recognition of foreign class ll alloantigens o the
graft y host CD8+ cells canclead to CTL mediated
killing.

21. • Cytokines secreted by TH cells play main role
• IL-2 IFN-ɣ and TNF-ɣβ ate important mediator of
graft rejection.
• IL-2 promotes T-cell proliferation and generally is
required to the generation of effector CTLs.

22. Types of rejection reaction
• Graft rejection reaction have various time courses
depending upon the type of tissue grafted and the
immune response involved
• Hyperacute rejection
• These reactions occur within first 24 hrs of
transplantation.
• Caused by pre-existing host serum antibodies
specific for antigen of Graft.

24. Continued....
• Acute rejection
• Begin in about 10days after transplantation
• T-cell mediated response is generated
• Chronic rejection
• Occurs from months to years after transplantation
• Includes both humoral and cell mediated response.

25. Immunosuppressive therapy
• General immunosuppressive therapy
• Specific immunosuppressive therapy

26. General immunosuppressive therapy
• Azathioprine (imuran), is a mitotic inhibitor which
diminish T-cell and B-cell proliferation by blocking
inosinic acid synthesis in S phase.
• Corticosteroids eg. Prednisone and dexamethasone
are used as anti-inflammatory agents.
• fungal metabolites like Cyclosporine A,
FK506(tacrolimus) inhibit transcription of IL-2 thus
blocking T-cell activation.

27. • Rapamycin blocks the proliferation and
differentiation of activated T-helper cells in G1
phase.
• Rapamycin and FK506 are 10-100 times stronger
than cyclosporine A.
• Lymphocytes are sensitive to X-rays thus X-
irradiation can be used to eliminate them in the
recipient before grafting.

28. • Specific immunosuppressive therapy
• Monoclonal antibodies can suppress graft-
rejection response
• Blocking co-stimulatory signals can induce
anergy

29. Immune tolerance to allograft
• Privileged sites accept antigenic mismatches:
anterior chamber of eyes, cornea, uterus, testes,
brain- absence of lymphatic vessels and in some
even blood vessels make them privileged site.
These sites does not produce immune response.
• Early exposure to alloantigens can induces specific
tolerance:

30. Clinical transplantation