TRANSPLANTATION.

1. TRANSPLANTATION
MATEEN IRFANSHA .

2. TRANSPLANTATION:-
The transfer (an organ or tissue) from one part of the body to another
or from one person (the donor) to another (the recipient).
Most common transplantation is blood transfusion.
The heart, kidneys, liver, lungs, pancreas, intestine, and thymus.
The kidneys are the most commonly transplanted organs,
followed closely by the liver and then the heart.
•TISSUES THAT CAN BETRANSPLANTED ARE:-
Tissues include bones, tendons (both referred to as
musculoskeletal grafts), cornea, skin, heart valves, and veins .
The cornea and musculoskeletal grafts are the most
commonly transplanted tissues.
•ORGANS THAT CAN BE TRANSPLANTED ARE :-

3. Classification of transplantation:-
• Autotransplantation (Autografts):-
– Grafts transplanted from one part of the body to another in
the same individual
– Sometimes this is done with surplus tissue, or tissue that
can regenerate
– E.g :- Skin grafts, Bone grafts.
• Isograft (Syngeneic grafts):-
– Grafts transplanted between two genetically identical
individuals of the same species.
– Isografts are differentiated from other types of transplants
because while they are anatomically identical to allografts,
they do not trigger an immune response..

4. • Allotransplantation (Allogeneic grafts ) :-
- Grafts transplanted between two genetically different individuals
of the same species ( living or cadaveric sources)
- Most human tissue and organ transplants are allografts. Due to the
genetic difference between the organ and the recipient, the
recipient's immune system will identify the organ as foreign and
attempt to destroy it, causing transplant rejection.
- E.g :- Kindney , Heart & Liver transplantation
•

5. •Xenotransplantation(Xenografts):-
-Grafts transplanted between individuals of
different species.
-A major barrier to xenogeneic
transplantation is the presence of natural
antibodies that cause hyperacute rejection.
-E.g:-porcine heart valve transplantation
&
fish to non-human primate transplant of
islet
•Split transplants :-
-Sometimes a deceased-donor organ, usually a liver, may
be divided between two recipients, especially an adult and a
child. This is not usually a preferred option because the
transplantation of a whole organ is more successful.

7. What is graft rejection?
The immunologic destruction of transplanted organs or tissues. The
rejection may be based on both cell-mediated and antibody-mediated
immunity against cells of the graft by a histoincompatible recipient.
• Grafts rejection is a kind of specific immune response.
• Grafts rejection:-
– First set rejection:-when skin is grafted between unrelated
or allogeneicindividuals (an allograft), the graft is initially
accepted but is then rejected about 10–13 days after grafting
(Fig.).This response is called a first-set rejection
•Allograft Rejection:-

8. -Second set rejection:- When a recipient that has previously
rejected a graft is regrafted with skin from the same donor, the
second graft is rejected more rapidly (6–8 days) in a second-set
rejection and the accelerated response is MHC-specific.

9. •Components of the Immune system involved in
graft Rejection :
1) Antigen presenting cells –
Dendritic cells
Macrophages
Activated B Cells
2) B cells and antibodies –
Preformed antibodies
Natural antibodies
Induced antibodies
3) T cells
4) Other cells –
Natural killer cells
Monocytes/Macrophages

10. Classification of Allograft Rejection:-
1. Host versus graft reaction (HVGR)
Conventional organ transplantation
2. Graft versus host reaction (GVHR)
Bone marrow transplantation
Immune cells transplantation
TYPES OF ALLOGRAFT REJECTION:-
1) Hyperacute rejection:-
.Occurrence time:-
Occurs within minutes to hours after host blood vessels are
anastomosed to graft vessels.
.Pathology :-
Thrombotic occlusion of the graft vasculature
Ischemia, denaturation, necrosis
1.Host versus graft reaction (HVGR)

11. Mechanisms:-
Preformed antibodies
1. Antibody against ABO blood type antigen
2. Antibody against VEC ( vascular endothelial cell)
antigen
3. HLA antigen

12. 2) Acute Rejection:-
Occurrence time :-
Occurs within days to 2 weeks after transplantation, 80-90% of
cases occur within 1 month.
Pathology :-
•Acute humoral rejection:-
Acute vasculitis manifested mainly by endothelial cell
damage
•Acute cellular rejection:-
Parenchymal cell necrosis along with infiltration of
lymphocytes and MΦ

13. Mechanisms
Vasculitis:-
IgG antibodies against alloantigens on endothelial cell
CDC
Parenchymal cell damage:-
•Delayed hypersensitivity mediated by CD4+Th1
•Killing of graft cells by CD8+Tc

14. 3) Chronic or late rejection:-
Occurrence time:-
Develops months or years after acute rejection reactions have
subsided

15. Mechanisms
-Not clear
-Extension and results of cell necrosis in acute rejection
-Chronic inflammation mediated by CD4+T cell/MΦ
Organ degeneration induced by non immune factors
Pathology:-
Fibrosis and vascular abnormalities with loss of graft
function

16. Transplantation antigens:-
•Major histocompatibility antigens :-
(MHC molecules, Main antigens of grafts
rejection ).
- Cause fast and strong rejection
-Difference of HLA types is the main
cause of human grafts rejection.
•Minor histocompatibility antigens:-
(Also cause grafts rejection, but slow and weak)
•Other alloantigens:-
(Human ABO blood group antigens).

17. Major Histocompatibility Complex (MHC)
•MHC Class I:-
•Three genes (HLA-A,
HLA-B, HLA-C) code
for the class- I MHC
proteins.
• Several HLA-D loci
determine the class II
MHC proteins i.e. DP,
DQ and DR
In humans, MHC resides on
the arm of chromosome 6
MHC Class I Antigens:-
•Class I MHC antigens are : HLA-A, HLA-
B and HLA-C
• These antigens are glycoproteins
found on surfaces of all nucleotide
human cells and on platelets
• Class I MHC antigens are involved of
MHC restriction of cell mediated
cytotoxicity
• Endogenously processed cytosolic
peptides in virus infected cells or tumor
cells are transported to the surface of the
cells
• They bind to MHC I molecules to be
recognized by cytotoxic T-cells which
then kill these cells
•MHC Class II:-

18. Major Histocompatibility Complex (MHC)
In humans, MHC resides on
the arm of chromosome 6
•MHC Class I:-
•Three genes (HLA-A,
HLA-B, HLA-C) code
for the class- I MHC
proteins.
• Several HLA-D loci
determine the class II
MHC proteins i.e. DP,
DQ and DR
•MHC Class II:-
•Class II antigens are: HLA-DP, HLA-
DQ, HLA-DR antigens
•These antigens are glycoproteins
found on the surface of
macrophages, B-cells, Dentritic cells,
langerhans cells of skin and activated
T cells
MHC Class II Antigens
• Helper T-cells recognize antigens on
antigen-presenting cells only when
the antigens are presented on the
surface of cells in association with
class II MHC
• Class II antigens react with the CD4
molecule on the helper T-cells which
secrete cytokines

19. Class I MHC and Class II MHC
MHC Class I MHC Class II
Nomenclature HLA-A, HLA-B, HLA-C HLA-DP, HLA-DQ,
HLA-DR
Found on All nucleated somatic
cells
Macrophages, B-cells,
Dentritic cells,
langerhans cells of skin
and activated T cells
Recognized by CD8 TC cells CD4 TH cells
Functions Presentation of Ag to TC
cells leading to
elimination of tumor or
infected host cell
Presentation of Ag to TH
cells which secrete
cytokines

20. Mechanism of graft rejection :-
1) Cell-mediated Immunity.
2) Humoral immunity.
1) Cell-mediated Immunity :-
• Recipient's T cell-mediated cellular immune response against
alloantigens on grafts.
• T cells of the recipient recognize the allogeneic MHC
molecules :
• Direct Recognition &
• Indirect Recognition

21. •Direct recognition :-
•Recognitio of an intact
MHC molecule displayed
by donor APC in the graft
•Involves both CD8+ and
CD4+ T cells. n
•Indirect recognition :-
• Donor MHC is processed
and presented by recipient
APC.
•Basically, donor MHC
molecule is handled like
any other foreign Ag.
• Involve only CD4+ T
cells.
•Antigen presentation by
class II MHC molecules.

22. Direct Recognition Indirect
Recognition
Allogeneic MHC
molecule
Intact allogeneic MHC
molecule
Peptide of allogeneic
MHC molecule
APCs Recipient APCs are not
necessary
Recipient APCs
Activated T cells CD4＋T cells and/or
CD8＋T cells
CD4＋T cells and/or
CD8＋T cells
Roles in rejection Acute rejection Chronic rejection
Degree of rejection Vigorous Weak
Difference between Direct Recognition and
Indirect Recognition

23. 2) Humoral immunity:-
– Ab’s produced against donor Ag can also mediate rejection
through two forms:
I. Hyperacute rejection:
• Immediate rejection soon after transplantation.
• Occurs when preformed antidonor Ab’s are present in
the circulation of the recipient.
II. Anti-HLA humoral Ab’s
• It develops concurrently with T-cell mediated rejection.
• Seen in recipients not previously sensitized to
transplantation antigens, exposure to the class I and class
II HLA antigens of the donor may evoke antibodies.
• The initial target of these antibodies in rejection appears to
be the graft vasculature.

24. •Caused by the reaction of grafted mature T-cells in the marrow
inoculum with alloantigens of the host.
•Acute GVHD:-
Characterized by epithelial cell death in the skin, GI tract, and
liver.
•Chronic GVHD:-
Characterized by atrophy and fibrosis of one or more of these same
target organs as well as the lungs.
Graft vs. Host Disease:-

25. Immunosuppressive Agents:-
Immunosuppression can be brought about by 3 different ways :-
1)Surgical ablation.
2)Total Lymphoid Irradiation.
3)Immunosuppressive drugs.
Immunosuppressive Drugs:-
Three main immunosuppressant drugs
1) Cyclosporins:- act by inhibiting T-cell activation, thus
preventing T-cells from attacking the transplanted organ.
2) Azathioprines:- disrupt the synthesis of DNA and RNA and
cell division.
Q.HOW TO PREVENT GRAFT REJECTION?

26. •Side-effect:-
• immunodeficiency, because the majority of them act non-selectively,
resulting in increased susceptibility to infections and
•Decreased cancer immunosurveillance.
• There are also other side-effects, such
as hypertension, dyslipidemia, hyperglycemia, peptic
ulcers, lipodystrophy, moon face, liver and kidney injury.
3) Glucocorticoids:-
•(Glucocorticoids suppress the cell-mediated immunity. They act by
inhibiting genes that code for the cytokines Interleukin 1 (IL-1), IL-
2,3,4,5,6,8, and TNF-γ,d most important of which is IL-2.
Smaller cytokine productn reduces the T cell proliferatn.
•Glucocorticoids also suppress the humoral immunity, causing B cells to
express smaller amounts of IL-2 and IL-2 receptors. This diminishes both
B cell clone expansion and antibody synthesis.

27. PRIMARY goal in organ transplantation:-
•The prevention/effective treatment of infection, d most common life-
threatening complication of long-term immunosuppressive therapy.
• immunosuppression-induced impairment of the inflammatory
response,which attenuates d sign & symptoms of invasive infection.
•Avoid the adverse effects of the antimicrobial drugs used for
prophylaxis and therapy, which result both from the duration of
therapy required and from interactions with the immunosuppressive
drugs
•Aim is to delineate the principles guiding infectious disease practice
in transplantation, emphasizing the prevention and early recognition
of infection and the avoidance of common drug-related toxic effects.

29. THANK U…..