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ORGAN
TRANSPLANTATION
& TYPES
SUBMITTED BY,
AKSHAYA ANIL
S 4 M.Sc BIOCHEMISTRY
DEPT.OF BIOCHEMISTRY
KERALA UNIVERSITY
1
Is a surgical operation in which a
failure or damaged organ in body is
removed and replaced with a functioning
one
ORGAN TRANSPLANTATION
2
HISTORY
3
• Initial problem with transplantation was immune
response against the transplanted organ
• Scientists realized that the problem of rejection didn't
occur when the organ donor and recipient were
identical twins. The genetic similarity appeared to
prevent the immune response
• In the late 1960s, doctors figured out a way to
perform transplants between nonrelatives by
suppressing the recipient's immune response with
drugs like cyclosporine
4
TIME LINES
5
 1954 - Joe Murray performed successful kidney transplants
between identical twins (Boston, MA, USA)
 1962 - Roy Calne demonstrated the effiency of azathioprine
in preventing rejection of kidney allografts (Boston, MA,
USA)
 1963 - Tom Starzl performed the first human liver transplant
(Denver, CO, USA)
 1966 - Richard Lillehei and William Kelly performed first
human whole organ pancreas transplant (along with a kidney
transplant) (Minneapolis, MN, USA)
 1967 - Christian Barnard performed the first human heart
transplant (Cape Town, South Africa)
 1968 - Fritz Derom performed the first human lung transplant
(Ghent, Belgium)
 1969 - Geoff Collins developed Collins solution – a new
kidney preservation solution
6
 1974 - David Sutherland and John Najarin performed the first
human pancreatic islet transplant (Minneapolis, MN, USA)
 1978 - Roy Calne introduced ciclosporin into clinical practice
(Cambridge, UK)
 1981 - Bruce Reitz and Norman Shumway performed the first
successful human heart-lung transplant (Stanford, CA, USA)
 1987 - Fokert Belzer and colleagues developed University of
Wisconsin (UW) solution – a new liver and pancreas preservation
solution (Wisconsin, USA)
 Kidney transplant was first undertaken in Nigeria in March 2000 in
a private hospital in Lagos (St Nicholas Hospital), with another two
units (in Ile-Ife and Kano) starting 2 years later
 The feat of the first Renal Transplantation to be undertaken by a
team of indigenous surgeons in any public Institution in Nigeria
was successfully carried out in the Department of Surgery of the
Obafemi Awolowo University Teaching Hospital in May 2002
7
 1974 - David Sutherland and John Najarin performed the first
human pancreatic islet transplant (Minneapolis, MN, USA)
 1978 - Roy Calne introduced ciclosporin into clinical practice
(Cambridge, UK)
 1981 - Bruce Reitz and Norman Shumway performed the first
successful human heart-lung transplant (Stanford, CA, USA)
 1987 - Fokert Belzer and colleagues developed University of
Wisconsin (UW) solution – a new liver and pancreas preservation
solution (Wisconsin, USA)
 Kidney transplant was first undertaken in Nigeria in March 2000 in
a private hospital in Lagos (St Nicholas Hospital), with another two
units (in Ile-Ife and Kano) starting 2 years later
 The feat of the first Renal Transplantation to be undertaken by a
team of indigenous surgeons in any public Institution in Nigeria
was successfully carried out in the Department of Surgery of the
Obafemi Awolowo University Teaching Hospital in May 2002
8
Worked on graft rejection and the discovered acquired
immune tolerance, fundamental to the practice of tissue
and organ transplants. For his works in immunology he is
regarded as the "father of transplantation".
SIR PETER MEDAWAR
9
He invented the first perfusion pump with
Charles A. Lindbergh opening the way to organ transplantation
ALEXIS CARREL
10
THOMAS EARL STARZL
An American physician, researcher, and expert
on organ transplants. He performed the
first liver transplants, and has often been referred to
as "the father of modern transplantation”
11
ORGANS TRANSPLANTED
12
TISSUE TRANSPLANTED
13
TYPES OF TRANSPLANTS
14
 Is the transplantation of tissues or even
particular proteins from one part of the body to
another in the same person
 A common example is the removal of a piece of bone
(usually from the hip) and its being ground into a
paste for the reconstruction of another portion of
bone skin grafts, vein extraction
AUTOGRAFT
15
 Is the transplantation of cells, tissues, or organs to a recipient
from a genetically non-identical donor of the same species.
 An immune response against an allograft or xenograft is
termed rejection
 Joint reconstruction in the knee and ankle,reconstruction due
to cancer or trauma,ridge augmentation in dental
procedure,shoulder repair,spinal fusion,urological
procedures,skin transplants,corneal transplants,heart
transplants,heart valves,lung transplantation,intestinal
transplantation (isolated small bowel, intestine & liver,
multivisceral),liver transplants,kidney transplants,pancreas
transplantation,islet cell transplantation,bone marrow
transplants,bone allograft,ligament or tendon allograft
ALLOGRAFT
16
ISOGRAFT
 Is a graft of tissue between two individuals who are
genetically identical (i.e. monozygotic twins).
 Transplant rejection between two such individuals virtually
never occurs, making isografts particularly relevant to organ
transplanations
 Patients with organs from their identical twins are incredibly
likely to receive the organs favorably and survive.
 Monozygotic twins have the same major histocompatibility
complex, leading to the low instances of tissue rejection by
the adaptive immune system
 Furthermore, there is virtually no incidence of graft-versus-
host disease.
17
XENOTRANSPLANTATION
 Is the transplantation of living cells, tissues
or organs from one species to another.
 Xenotransplantation of human tumor cells
into immunocompromised mice is a research
technique frequently used in pre-clinical oncology
research
 Porcine heart valves, which are quite common and
successful
18
19
SPLIT TRANSPLANT
 A deceased-donor organ, usually a liver, may be
divided between two recipients, especially an adult
and a child.
 Not usually a preferred option because the
transplantation of a whole organ is more successful.
20
ORTHOTOPIC & HETEROTOPIC
GRAFT
 Orthotopic graft: a graft placed in its normal
anatomical site
 Heterotopic graft: a graft placed in a site different
from that where the organ is normally located
21
TYPES OF DONARS
22
LIVING DONOR:
 donor remains alive
 donates a renewable tissue, cell or fluid(ex: skin, blood)
or donates an organ(primarily single kidney donation,
partial donation of liver, lung lobe)
DECEASED DONOR:
 donors are people who have been declared brain-dead
and whose organs are kept viable by ventilators or other
mechanical mechanism until they can be excised for
transplantation
23
SUCCESSFUL TRANSPLANTS
 1908- First transplant of a knee
 1909- First recorded kidney transplant,animal to human
 1936- First human-to-human kidney transplant
 1953- First successful surgery using heart-lung bypass
 1954- First successful kidney transplant
 1963- First successful lung transplant
 1967- First successful liver transplant
 1968- First successful heart transplant in the U.S
 1973- First successful bone marrow transplant
 1998- First successful hand transplant
24
 The success of transplants today is due in large part
to control of the rejection process
 As with the body's reaction to an infection, graft
rejection is triggered when specific cells of the
transplant recipient, namely T and B lymphocytes,
recognize foreign antigens
25
EFFECTOR MECHANISM OF
REJECTION
26
 HLA antigens expressed by graft cells activate T cells and stimulate
them to proliferate in response to interleukin-2 (IL- 2) and other T-cell
growth factors.
 Activated CD4 T cells, through release of cytokines, play a central role
in orchestrating the various effector mechanisms responsible for graft
rejection.
 The cellular effectors of graft rejection include cytotoxic CD8 T cells,
that recognise donor HLA class I antigens expressed by the graft and
cause target cell death by releasing lytic molecules such as perforin
and granzyme.
 Graft infiltrating CD4 T cells, which recognise donor HLA class II
antigens, mediate direct target cell damage and are also able, by
releasing pro-inflammatory cytokines such as interferon-ɣ, to recruit
and activate macrophages that act as non-specific effector cells.
 Finally, CD4 T cells provide essential T-cell help for B lymphocytes
that differentiate into plasma cells and produce allo-antibodies that
bind to graft antigen and induce target cell injury directly or through
antibody-dependent, cell-mediated cytotoxicity
27
CLINICAL IMMUNOSUPPRESSION
28
Induction immunosuppression
refers to the drugs administered immediately
post transplant to induce immunosuppression
Maintenance immunosuppression
refers to the drugs administered to maintain
immunosuppression once recipients have recovered
from the operative procedure.
Individual drugs can be categorized as either biologic
or non-biologic agents.
 Biologic agents consist of antibody preparations
directed at various cells or receptors involved in the
rejection process; they generally are used in
induction (rather than maintenance) protocols.
 Non-biologic agents form the mainstay of
maintenance protocols
29
 ORGAN HARVEST
• Various organ preservative solutions are available for flushing
organs before cold storage.
• They all contain impermeants to limit cell swelling, buffers to
counter acidosis and electrolytes, the composition of which
reflects that of intracellular rather than extracellular fluid.
• Commonly used preservation solutions include University of
Wisconsin (UW) solution and Euro-Collins solution, but there are
many others.
30
IMPACT OF
TRANSPLANTATION ON
PATIENTS
31
 Infections
Attempts to suppress the immune response to avoid graft rejection a weaken the
ability of the body to combat infectious agents .
 Cancer
Suppressing the host's immune responses also increases the risk of cancer.
 Hypertension
Is common immediately after transplant. Certain anti-rejection medication
contribute to hypertension.
 Shingles
People with weakened immune systems, such as transplant recipients treated with
immunosuppressive drugs, risk developing shingles. Shingles is a painful infection
of the central nervous system
 Diabetes
Some anti-rejection medicines are known to cause high blood sugar. Although it
is typically a temporary condition after transplantation, it is more common in
patients who have a family history of diabetes and patients who are over weight.
32
33
34
35
Breeding transgenic animals
Injecting a small amount of DNA mimicking a human gene
sequence into a fertilized egg
Then implanting egg into surrogant cow
Transgenic pig produce human proteins that make it difficult
for the human immune system to identify
1,TRANSGENIC ANIMALS
36
2,TOLERANCE APPROACH
Administering pig bone marrow cells to the recipient prior
to organ transplantation
Progenitor immune cells develops into mature immune
cells in the recipient’s body
37
“Organ transplantation gives thousands of
children and adults each year a renewed chance
at living full and active lives. However, the need
for organs and tissue outweighs their availability.
Committing to be an organ donor is a generous
decision that can save the lives of up to eight
individuals, and even more if a donor can give
corneas and tissue. Almost anyone, regardless of
age, race or gender, can become an organ and
tissue donor”
38
REFERENCE
 Organ Transplantation: A Clinical Guide,edited by
Andrew A. Klein, Clive J. Lew
 A History of Organ Transplantation: Ancient
Legends to Modern Practice
Organ ,David Petechuk David
 Organ transplantation,Hamiltonis,
Joren C. Madsen
39
THANK YOU…..
40

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Organ transplantation

  • 1. ORGAN TRANSPLANTATION & TYPES SUBMITTED BY, AKSHAYA ANIL S 4 M.Sc BIOCHEMISTRY DEPT.OF BIOCHEMISTRY KERALA UNIVERSITY 1
  • 2. Is a surgical operation in which a failure or damaged organ in body is removed and replaced with a functioning one ORGAN TRANSPLANTATION 2
  • 4. • Initial problem with transplantation was immune response against the transplanted organ • Scientists realized that the problem of rejection didn't occur when the organ donor and recipient were identical twins. The genetic similarity appeared to prevent the immune response • In the late 1960s, doctors figured out a way to perform transplants between nonrelatives by suppressing the recipient's immune response with drugs like cyclosporine 4
  • 6.  1954 - Joe Murray performed successful kidney transplants between identical twins (Boston, MA, USA)  1962 - Roy Calne demonstrated the effiency of azathioprine in preventing rejection of kidney allografts (Boston, MA, USA)  1963 - Tom Starzl performed the first human liver transplant (Denver, CO, USA)  1966 - Richard Lillehei and William Kelly performed first human whole organ pancreas transplant (along with a kidney transplant) (Minneapolis, MN, USA)  1967 - Christian Barnard performed the first human heart transplant (Cape Town, South Africa)  1968 - Fritz Derom performed the first human lung transplant (Ghent, Belgium)  1969 - Geoff Collins developed Collins solution – a new kidney preservation solution 6
  • 7.  1974 - David Sutherland and John Najarin performed the first human pancreatic islet transplant (Minneapolis, MN, USA)  1978 - Roy Calne introduced ciclosporin into clinical practice (Cambridge, UK)  1981 - Bruce Reitz and Norman Shumway performed the first successful human heart-lung transplant (Stanford, CA, USA)  1987 - Fokert Belzer and colleagues developed University of Wisconsin (UW) solution – a new liver and pancreas preservation solution (Wisconsin, USA)  Kidney transplant was first undertaken in Nigeria in March 2000 in a private hospital in Lagos (St Nicholas Hospital), with another two units (in Ile-Ife and Kano) starting 2 years later  The feat of the first Renal Transplantation to be undertaken by a team of indigenous surgeons in any public Institution in Nigeria was successfully carried out in the Department of Surgery of the Obafemi Awolowo University Teaching Hospital in May 2002 7
  • 8.  1974 - David Sutherland and John Najarin performed the first human pancreatic islet transplant (Minneapolis, MN, USA)  1978 - Roy Calne introduced ciclosporin into clinical practice (Cambridge, UK)  1981 - Bruce Reitz and Norman Shumway performed the first successful human heart-lung transplant (Stanford, CA, USA)  1987 - Fokert Belzer and colleagues developed University of Wisconsin (UW) solution – a new liver and pancreas preservation solution (Wisconsin, USA)  Kidney transplant was first undertaken in Nigeria in March 2000 in a private hospital in Lagos (St Nicholas Hospital), with another two units (in Ile-Ife and Kano) starting 2 years later  The feat of the first Renal Transplantation to be undertaken by a team of indigenous surgeons in any public Institution in Nigeria was successfully carried out in the Department of Surgery of the Obafemi Awolowo University Teaching Hospital in May 2002 8
  • 9. Worked on graft rejection and the discovered acquired immune tolerance, fundamental to the practice of tissue and organ transplants. For his works in immunology he is regarded as the "father of transplantation". SIR PETER MEDAWAR 9
  • 10. He invented the first perfusion pump with Charles A. Lindbergh opening the way to organ transplantation ALEXIS CARREL 10
  • 11. THOMAS EARL STARZL An American physician, researcher, and expert on organ transplants. He performed the first liver transplants, and has often been referred to as "the father of modern transplantation” 11
  • 15.  Is the transplantation of tissues or even particular proteins from one part of the body to another in the same person  A common example is the removal of a piece of bone (usually from the hip) and its being ground into a paste for the reconstruction of another portion of bone skin grafts, vein extraction AUTOGRAFT 15
  • 16.  Is the transplantation of cells, tissues, or organs to a recipient from a genetically non-identical donor of the same species.  An immune response against an allograft or xenograft is termed rejection  Joint reconstruction in the knee and ankle,reconstruction due to cancer or trauma,ridge augmentation in dental procedure,shoulder repair,spinal fusion,urological procedures,skin transplants,corneal transplants,heart transplants,heart valves,lung transplantation,intestinal transplantation (isolated small bowel, intestine & liver, multivisceral),liver transplants,kidney transplants,pancreas transplantation,islet cell transplantation,bone marrow transplants,bone allograft,ligament or tendon allograft ALLOGRAFT 16
  • 17. ISOGRAFT  Is a graft of tissue between two individuals who are genetically identical (i.e. monozygotic twins).  Transplant rejection between two such individuals virtually never occurs, making isografts particularly relevant to organ transplanations  Patients with organs from their identical twins are incredibly likely to receive the organs favorably and survive.  Monozygotic twins have the same major histocompatibility complex, leading to the low instances of tissue rejection by the adaptive immune system  Furthermore, there is virtually no incidence of graft-versus- host disease. 17
  • 18. XENOTRANSPLANTATION  Is the transplantation of living cells, tissues or organs from one species to another.  Xenotransplantation of human tumor cells into immunocompromised mice is a research technique frequently used in pre-clinical oncology research  Porcine heart valves, which are quite common and successful 18
  • 19. 19
  • 20. SPLIT TRANSPLANT  A deceased-donor organ, usually a liver, may be divided between two recipients, especially an adult and a child.  Not usually a preferred option because the transplantation of a whole organ is more successful. 20
  • 21. ORTHOTOPIC & HETEROTOPIC GRAFT  Orthotopic graft: a graft placed in its normal anatomical site  Heterotopic graft: a graft placed in a site different from that where the organ is normally located 21
  • 23. LIVING DONOR:  donor remains alive  donates a renewable tissue, cell or fluid(ex: skin, blood) or donates an organ(primarily single kidney donation, partial donation of liver, lung lobe) DECEASED DONOR:  donors are people who have been declared brain-dead and whose organs are kept viable by ventilators or other mechanical mechanism until they can be excised for transplantation 23
  • 24. SUCCESSFUL TRANSPLANTS  1908- First transplant of a knee  1909- First recorded kidney transplant,animal to human  1936- First human-to-human kidney transplant  1953- First successful surgery using heart-lung bypass  1954- First successful kidney transplant  1963- First successful lung transplant  1967- First successful liver transplant  1968- First successful heart transplant in the U.S  1973- First successful bone marrow transplant  1998- First successful hand transplant 24
  • 25.  The success of transplants today is due in large part to control of the rejection process  As with the body's reaction to an infection, graft rejection is triggered when specific cells of the transplant recipient, namely T and B lymphocytes, recognize foreign antigens 25
  • 27.  HLA antigens expressed by graft cells activate T cells and stimulate them to proliferate in response to interleukin-2 (IL- 2) and other T-cell growth factors.  Activated CD4 T cells, through release of cytokines, play a central role in orchestrating the various effector mechanisms responsible for graft rejection.  The cellular effectors of graft rejection include cytotoxic CD8 T cells, that recognise donor HLA class I antigens expressed by the graft and cause target cell death by releasing lytic molecules such as perforin and granzyme.  Graft infiltrating CD4 T cells, which recognise donor HLA class II antigens, mediate direct target cell damage and are also able, by releasing pro-inflammatory cytokines such as interferon-ɣ, to recruit and activate macrophages that act as non-specific effector cells.  Finally, CD4 T cells provide essential T-cell help for B lymphocytes that differentiate into plasma cells and produce allo-antibodies that bind to graft antigen and induce target cell injury directly or through antibody-dependent, cell-mediated cytotoxicity 27
  • 29. Induction immunosuppression refers to the drugs administered immediately post transplant to induce immunosuppression Maintenance immunosuppression refers to the drugs administered to maintain immunosuppression once recipients have recovered from the operative procedure. Individual drugs can be categorized as either biologic or non-biologic agents.  Biologic agents consist of antibody preparations directed at various cells or receptors involved in the rejection process; they generally are used in induction (rather than maintenance) protocols.  Non-biologic agents form the mainstay of maintenance protocols 29
  • 30.  ORGAN HARVEST • Various organ preservative solutions are available for flushing organs before cold storage. • They all contain impermeants to limit cell swelling, buffers to counter acidosis and electrolytes, the composition of which reflects that of intracellular rather than extracellular fluid. • Commonly used preservation solutions include University of Wisconsin (UW) solution and Euro-Collins solution, but there are many others. 30
  • 32.  Infections Attempts to suppress the immune response to avoid graft rejection a weaken the ability of the body to combat infectious agents .  Cancer Suppressing the host's immune responses also increases the risk of cancer.  Hypertension Is common immediately after transplant. Certain anti-rejection medication contribute to hypertension.  Shingles People with weakened immune systems, such as transplant recipients treated with immunosuppressive drugs, risk developing shingles. Shingles is a painful infection of the central nervous system  Diabetes Some anti-rejection medicines are known to cause high blood sugar. Although it is typically a temporary condition after transplantation, it is more common in patients who have a family history of diabetes and patients who are over weight. 32
  • 33. 33
  • 34. 34
  • 35. 35 Breeding transgenic animals Injecting a small amount of DNA mimicking a human gene sequence into a fertilized egg Then implanting egg into surrogant cow Transgenic pig produce human proteins that make it difficult for the human immune system to identify 1,TRANSGENIC ANIMALS
  • 36. 36 2,TOLERANCE APPROACH Administering pig bone marrow cells to the recipient prior to organ transplantation Progenitor immune cells develops into mature immune cells in the recipient’s body
  • 37. 37
  • 38. “Organ transplantation gives thousands of children and adults each year a renewed chance at living full and active lives. However, the need for organs and tissue outweighs their availability. Committing to be an organ donor is a generous decision that can save the lives of up to eight individuals, and even more if a donor can give corneas and tissue. Almost anyone, regardless of age, race or gender, can become an organ and tissue donor” 38
  • 39. REFERENCE  Organ Transplantation: A Clinical Guide,edited by Andrew A. Klein, Clive J. Lew  A History of Organ Transplantation: Ancient Legends to Modern Practice Organ ,David Petechuk David  Organ transplantation,Hamiltonis, Joren C. Madsen 39