Organ transplantation involves transferring a whole or partial organ from a donor to a recipient in need of replacement of a damaged or failing organ. Major transplantable organs include the liver, kidney, heart, lungs, pancreas and intestine. Transplant rejection is a major complication that occurs when the recipient's immune system attacks the donor organ. The main types of rejection are hyperacute, acute vascular, acute cellular and chronic rejection. Rejection is combatted using immunosuppressive drugs that inhibit lymphocyte proliferation and activation such as corticosteroids, calcineurin inhibitors, antiproliferatives and anti-T cell agents. With advances in immunosuppression and organ matching, transplantation has become an established treatment for end-stage organ

1. TRANSPLANT
REJECTION
BY: RAJINA SHAKYA
MN 2ND YEAR
MNC

2. ORGAN TRANSPLANTATION
• Organ transplantation is moving of a whole or partial organ from one body
to another for purpose of replacing the recipients damaged or failing organ
with a healthy, working organ.
• Organ transplants – life saving
• Tissue transplants – life enhancing
• Donor: individual who provides organ , may be living or deceased
• Recipient : individual who receives organ

3. ORGAN TRANSPLANTATION
• Definitive treatment of end stage organ disease.
• Solid organs as well as cells (pancreatic islet cells), bowel and multi-
organ transplants
• Complications after transplantation depend upon organ transplanted,
genetic disparity between recipient and donor.

4. TRANSPLANTABLE ORGANS
• Liver
• Kidney
• Cornea
• Pancreas
• Lung
• Heart
• Intestine
• Face
• Bone marrow

5. TYPES OF TRANSPLANTATION
• Auto graft : from one site to another in same individual
• Iso-graft: transfer between genetically identical (twins)
• Allograft: transfer between genetically different but same species
• Xenograft: transfer between one species to another
• Split transplant : organ of deceased transferred to 2 recipient
• Domino transplant: complete set of organ transplant eg. Both lungs in
cystic fibrosis

6. TRANSPLANT REJECTION
• Solid organ transplantation inevitably stimulates an aggressive immune
response by the recipient, unless the transplant is between monozygotic
twins.
• Nature of rejection response is determined by
 disparity between recipient and donor
Immune status of host
Nature of tissue transplanted
Difference between donor and recipient HLA(human leucocyte antigen)
proteins

7. CNTD….
• Extensive polymorphism of HLA proteins - invariably recognized as
foreign by the recipient immune system unless active attempt has been
made to minimize incompatibility.
• Compatibility at all HLA loci decreases
Acute rejection
Improves graft survival
Allows use of less intense immunosuppressive protocols

8. TRANSPLANT REJECTION
• Components of immune system involved in transplant rejection
1. Antigen presenting cells: dendritic cells, macrophages, activated B-cells
2. B-cells and antibodies
3. T-cells
4. Other cells : natural killer cells and monocytes

9. CNTD…
• Besides rejection reaction, a peculiar problem occurring
especially in bone marrow transplantation is Graft Versus
Host.
• results when immunocompetent cells are transplanted to
an immuno-deficient recipient
• Clinical features: fever, weight loss, anemia,dermatitis,
diarrhea, pneumonia, hepatosplenomegaly.

10. MECHANISMS OF GRAFT REJECTION
Cell mediated immune reactions:
mediated by T-cells
• Recipients lymphocytes get contact with donor HLA
antigens
• T-cells get sensitized becomes cytotoxic T-cells (CD8+)
and hypersensitivity reaction initiated by Helper T-
cells(CD4+)
• Attack and destroy graft tissue.

11. CNTD…
• Humoral immune reactions:
• Preformed circulating antibodies due to pre-sensitization
before transplantation eg. Blood transfusions
• In non-sensitized, by complement dependent cytotoxicity,
antibody –dependent cell mediated cytotoxicity and
antigen-antibody complexes.

12. CLASSIFICATION OF TRANSPLANT REJECTION
Type: Time Pathological
findings
Mechanism Treatment
Hyper-acute
rejection
Minutes to
hour after hosts
blood vessels
are
anastomised
Thrombosis
necrosis
Performed antibody and
complement activation (type II
hypersensitivity
none
Acute
vascular
rejection
5-30 days Vasculitis T and B lymphocytes and
antibody
Increase
immunosuppression
Acute
cellular
rejection
5-30 days Cellular infiltration CD4 and CD8 T cells (type IV
hypersensitivity)
Increase
immunosuppression
Chronic
allograft
> 30 days Fibrosis, scarring Immune and non-immune
mechanisms
Minimize drug toxicity,
control hypertension and
hyperlipidaemia

13. HYPER-ACUTE REJECTION
• Results in rapid and irreversible destruction of the graft.
• Mediated by pre-existing recipient antibodies against donor blood
group antigens (abo incompatibility) or donor HLA antigens, which arise
as a result of previous exposure through transplantation, blood
transfusion or pregnancy.
• Very rarely seen in clinical practice as the use of abo matching, screening
for anti-hla antibodies, and pre-transplant cross-matching ensures the
prior identification of recipients with antibodies against a potential donor

14. ACUTE VASCULAR REJECTION
• Mediated by antibody formed after transplantation.
• It is more curtailed than the hyper-acute response because of the use of
inter-current immunosuppression, but it is also associated with reduced graft
survival.
• Aggressive immunosuppressive therapy is indicated,
• Physical removal of antibody through plasmapheresis may be effective.
• Not all post-transplant anti-donor antibodies cause graft damage; their
consequences are determined by specificity and ability to trigger the
complement cascade

15. ACUTE CELLULAR REJECTION
• The most common form of graft rejection.
• It is mediated by activated t lymphocytes which recognize donor antigens.
• This results in deterioration in graft function, and if allowed to progress,
may cause fever, pain and tenderness over the graft.
• Acute cellular rejection is usually amenable to increased
immunosuppressive therapy

16. CHRONIC ALLOGRAFT FAILURE
• Also known as chronic rejection, is a major cause of graft loss.
• It is associated with proliferation of transplant vascular smooth muscle,
interstitial fibrosis and scarring.
• The pathogenesis is poorly understood, but contributing factors
include immunological damage caused by subacute rejection,
hypertension, hyperlipidemia and chronic drug toxicity.

17. REJECTION TREATMENT
• Hyper –acute an acute rejections are treated by removal of tissue or
organ
• Chronic rejection is considered irreversible and can be treated only by
re-transplantation
• Immunosuppressive therapy:

18. IMMUNO-SUPPRESIVE THERAPY:
Drug Mechanism of action Major adverse effects
Anti-proliferative agents
e.g. azathioprine,
mycophenolate mofetil
Inhibit DNA synthesis: block lymphocyte
proliferation and cytokine synthesis
May be directly cytotoxic at high doses
Increased susceptibility to infection
Leucopenia
Hepatotoxicity
Calcineurin inhibitors
e.g. ciclosporin, tacrolimus
Inhibit T-cell signaling: prevent lymphocyte
activation and block cytokine transcription
Increased susceptibility to infection
Hypertension
Nephrotoxicity
Diabetogenic (especially tacrolimus)
Gingival hypertrophy, hirsutism
(ciclosporin)
Corticosteroids Decrease phagocytosis and release of
proteolytic enzymes; decrease lymphocyte
activation and proliferation; decrease
cytokine production; decrease antibody
production
Increased susceptibility to infection
Anti-T-cell induction agents
e.g. anti-thymocyte globulin
(ATG), anti-CD3 monoclonal
Depletion or blockade of T cells by
antibodies to cell surface proteins
Profound non-specific
immunosuppression
Increased susceptibility to infection

19. SUCCESSFUL TRANSPLANTATIONS
• 1905: first successful cornea transplant
• 1954: first successful kidney transplant
• 1967: first successful heart , liver transplant
• 2008: first baby born from transplanted ovary
• 2013: first successful entire face transplantation

20. • Robbins textbook of pathology
• Davidson’s principle and practice of medicine, 20 edition
• Harsh mohan. Textbook of pathology. 6th edition
• https://www.slideshare.net/rashmikumari26/organ-transplantation-59297872
• http://www.who.int/transplantation/organ/en/

21. •Thank you