a brief description about transplantation immunology.

2. •Transplantation, the term used in immunology,
refers to the act of transferring cells, tissues or
organs from one site to another.

3. •Alexis Carrel reported the first systematic study of
transformation in 1908. He interchanged both kidneys in a
series of nine cats. Some of those receiving kidneys from
other cats maintained urinary output for up to 25 days.
Although all the cats eventually died but the experiment
established that a transplanted organ could carry out its
normal function in recipient.

4. •The first human kidney transplant, attempted in 1935 by a
Russian surgeon, failed because there was a mismatch of blood
types between donor and recipient.
•The first successful human kidney transplant, which was
between identical twins, was accomplished in Boston in 1954.
•Today kidney, heart, pancreas, lung, liver bone-marrow and
cornea transplantation are performed among non identical
individuals with ever increasing frequency and success.

5. The degree of immune response to a graft varies with the
type of graft. The following terms are used to denote
different types of transplants:
1. Autograft or autogeneic graft
2. Syngraft or isograft or isogeneic graft
3. Allograft or allogeneic graft
4. Xenograft or xenogeneic graft

6. Autograft refers to a graft that takes place within the same
individual. In autograft, a tissue of an individual is removed
from one site and implanted in another site of the same
individual. Its basically used in plastic surgery and
orthopedic surgery. Transferring of healthy skin to burnt area
and use of healthy blood vessels to replace blocked
coronary arteries are examples of frequently used
autografts.
The ag present in autograft is same as that present in body.
Hence the immune system recognizes the autograft antigen
as self ag and no immune response is elicited. As a result
autrograft can survive for life long unless there is an infection
or a trauma or a blockage or circulation, that prevent the
survival of the host.

7. Isograft is a graft that takes place between two genetically
identical individuals of the same species. It is a graft
between identical twins or between inbred strains of the
same species. Like a isograft can be performed between
genetically identical twins in human (Monozygotic twins).
In isograft the histocompatibility ag’s are identical. Hence the
graft can survived and is not rejected.

8. Allograft is the transfer of tissues between two genetically
distinct members of same species. The allograft was
formerly named as homograft. In mice an allograft is
performed by transferring tissue or an organ from one strain
to another.
In allograft, the histocompatibility antigens are dissimilar.
Hence an immune response is elicited and the graft is
rejected.
In humans, organ grafts from one individual to another are
allografts unless the donor and recipient are identical twins.

9. Xenografts is a graft or transfer of tissues between two
individuals of two different species. E.g. the graft of a
baboon heart into a human. This is because of significant
shortage in donated organs.
In xenograft, the histocompatibility complex ag’s are so
different that the graft is more vigorously rejected than in
allograft.

10. •When transplantation is made between genetically
identical individuals the graft survives and lives as healthy
as it is in original place.
•When the graft tissue remains alive, it is said to be
accepted and the process is called graft acceptance.
•The graft is accepted because the antigens of the graft and
host are identical and hence there is no immune response.
Thus the graft is due to the presence of similar type of
antigens.

11. •When transplantation is made between genetically distinct
individuals, the graft tissue dies and decays. When the graft
tissue dies, the graft is said to be rejected and the process is
called graft rejection.
•The graft is rejected because the antigens of the graft and
host are different and an immune response is elicited leading
to the death of the graft tissue.
•The immune reaction leading to graft rejection may be of
two types. They are 1. graft versus host reaction and 2. host
versus graft reaction.

13. •In some instances, the graft tissue elicits an immune
response against the host antigens. This immune response
is called graft versus host reaction. The graft versus host
reaction brings about damage to the host and host cells.
•The process graft rejection can be divided into two stages:
1. a sensitization phase, in which antigen reactive
lymphocytes of the recipient proliferate in response to allo-
antigen on the graft and 2. an effector stage in which
immune destruction of the graft takes place.

14. •During the sensitization phase, CD4+ and CD8+ T cells
recognize alloantigens express on the cell of the foreign
graft and proliferate in response.
•Both major and minor histocompatibility alloantigens can be
recognized. The response to major histocompatibility
antigens involves recognition of both the donor MHC
molecule and an associated peptide ligand in the cleft of the
MHC colecule.
•A host TH cell becomes activated when it interacts with an
antigen-presenting cell that both expresses an appropiate
antigenic ligand-MHC molecule complex and provides the
requisite co-stimulatory signals.

15. •Depending on the tissue, different populations of cells
within a graft may function as APCs. Because dendritic cells
are found in most tissues and because they constitutively
express high level of class II MHC molecules, dendritic cells
generally serve as the major APC in grafts.
•APCs of host origin can also migrate into a graft and
endocytose the foreign alloantigens and present them as
processed peptide together with self MHC molecules to TH
cells.
•In some organ and tissue grafts a population of donor
APCs called passenger leukocytes has been shown to
migrate from graft to the regional lymph nodes.

16. •These passenger leukocytes are dendritic cells, which
express high levels of class II MHC molecules. But
passenger leukocytes are not only one involved in immune
stimulation.
•Recognition of the alloantigens expressed on the cells of a
graft induces vigorous T-cell proliferation in the host.
•Both dendritic cells and vascular endothelial cells from an
allogeneic graft induce host T-cell proliferation.
•The major proliferating cell is CD4+ T cell. This amplified
population of activated TH cell is thought to play the central
role in inducing the various effector mechanism of allograft
rejection.

17. •A variety of effector mechanisms participate in allograft
rejection. The most common are cell mediated reactions
involving delayed type hypersensitivity and CTL(cytotoxic T
lymphocyte) mediated cytotoxicity ; less common
mechanisms are antibody-plus-compliment lysis and
destruction by antibody dependent cell mediated cytotoxicity
(ADCC).
•The hallmark of graft rejection involving cell mediated
reactions is an influx of T-cell and macrophages into the
graft.
•Infiltration can happen by delayed type hypersensitivity
response also in which cytokines

18. produced by TDTH cells promote macrophage infiltration.
•Recognition of foreign class I alloantigens on the graft by
host CD8+ cells can lead to CTL mediated killing. In some
cases CD4+ T cells that function as class II MHC restricted
cytotoxic cells mediated graft rejection.
•In each of these mechanisms cytokines secreted by TH cells
play a central role. For example IL-2, IFN-γ, and TNF-β are
important mediator for graft rejection.
•IL-2 promotes T-cell proliferation and necessary for
generation of effector CTLs.
•IFN-γ is central to the development of a DTH response,
promoting the influx of macrophages into the graft.

19. •TNF-β has been shown to have a direct cytotoxic effect on the
cells of a graft.

20. Effector Mechanism

21. •Graft-rejection reactions have various time courses
depending upon the type of tissue or organ grafted and the
immune response involved.
Three major types of rejection reaction are:
1. Hyper acute rejection: mediated by pre-existing host serum
antibodies specific for antigens of graft.
2. Acute graft: in this TH cell and/or CTLs mediated tissue
damage is there.
3. Chronic: in this both cellular and humoral immune
components are involved provided by recepient.

22. •Xenotransplantation is transfer of tissue or organs between
individuals of purely different species. E.g., the graft of a
baboon heart into human.
•Because of the significant shortages in donated organs,
raising animals for specific purpose of serving as organ
donors for human under serious consideration.
•Alexis Carrel with Charles A. Lindberg 1st opened the way to
organ transplantation. ‘Xenos’ this greek word means
stranger.
•The earliest transplantation of Chimpanzee kidneys into
humans date back to 1964. since that time several infrequent
attempts at kidney, liver and bone marrow transplantation from
primates to humans have been made. But no attempts met
with great success.

23. •In 1993, T.E. Starzl performed two liver transplants from
baboon into liver failure patients. Both patients died, one after
26 days and another after 70 days.
•In 1994 a pig liver was transplanted into a patient of acute
hepatic failure. The liver worked only for 30 hrs. before it was
rejected by hyper acute rejection.
•In 1995, baboon bone marrow was infused into an HIV
infected man with the aim of boosting his weakened immune
system with the baboon immune cell, which do not become
infected with the virus. Although there were no complications
from the transplant, the baboon bone marrow did not appear
to established itself in the recepient.

24. •a major problem with xenotransplants is that immune rejection
is often quite vigorous, even when recipient is treated with
potent immunosuppressive drugs such as FK-506 or
rapamycin.
•The major response involves the action of humoral antibody
and compliment, leading to the development of a hyperacute
rejection.
•In addition there is general concern that xenotransplantation
has potential of spreading pathogens from donor to recipient,
these pathogens could potentially cause disease; known as
xenozoonoses which are fatal for human.

25. •Immunosuppressive therapy is dependent on immunosuppressive
agents or drugs. Immunosuppressant drugs are a class of drugs that
suppress or reduce the strength of the body’s immune system. They
are also called anti-rejection drugs. One of the primary uses of
immunosuppressant drugs is to lower the body’s ability to reject a
transplanted organ, such as a liver, heart or kidney.
•But the majority of these agents have an overall
immunosuppressive effect on body. This is the main drawback of
these therapy. Patients long term on immunosuppressive drug are at
increased risk of cancer, hypertension and bone disease.
•Azathioprine, cyclosporine, corticosteroids such as prednisone are
some of the examples of immunosuppressive drugs.