TRANSPLANTATION GRAFT ORGAN TRANSPLANT HEART, KIDNEY, LIVER, LUNG FAILURE HISTORY TYPES OF TRANSPLANT ALLOGRAFT XENOGRAFT ISOGRAFT ALLOGRAFT TYPES OF DONOR GRAFT ACCEPTANCE GRAFT REJECTION ROLE OF T CELL GENETICS RECOGINITION OF ALLOANTIGENS EFFECT OF HLA MATCHING ROLE OF BLOOD GROUPS MECHANISM OF ACCEPTANCE MECHANISM OF REJECTION STAGES OF REJECTION GRAFT VS HOST REACTION MANIFESTATIONS PREVENTION OF REJECTION IMMUNOSUPPRESION

1. TRANSPLANTATION MEDICINE
DR PRIYANKA
ORAL MEDICINE AND RADIOLOGY

2. TRANSPLANTATION
 An act of transferring cells, tissues, or organs called GRAFT
(TRANSPLANT) from one site or individual (DONOR) into another
(usually different individual).
 Failure or damaged organ in human body is removed and replaced with
functioning one.
 Heart, kidneys, liver, lungs, pancreas, intestine and thymus
 KIDNEYS are most commonly transplanted organs followed by liver and
then heart

3. HISTORY
 SIR PETER MEDAWAR- FATHER OF TRANSPLANTATION
worked on graft rejection and acquired immune tolerance – showed that
skin allograft between two mice are rejected
 ALEXIS CARREL – awarded noble prize – worked on vascular suture
and transplantation of blood vessels and organs
 BRUCE REITZ- 1981, first successful heart lung transplant, credited
patients recovery to cyclosporine A
 DR EDUARD ZIRM – first successful corneal transplant, 1905

4. TYPES OF
TRANSPLANTS
 Autograft- transplant of tissues from one to oneself (skin graft, healthy blood
vessels to blocked coronary arteries)
 Antigen present is same as that present in body
 So immune system recognise this as a self antigen
 Autograft survive through out life
 Allograft- transplant between two genetically non identical members of same
species.
 Allograft histocompatibility antigens are dissimilar hence immune
response is elicited and graft is rejected
 Isograft- transplant from donor to genetically identical recipient (identical
twin) – don’t trigger an immune response as they are anatomically identical to
allograft
 Xenograft- transplant from one species to another- extremely dangerous
because of increased risk of non compatibility, rejection and disease carried in
tissue

6. TYPES OF
DONORS
 LIVING DONOR- donor remains alive and donates a renewable tissue,
cell or fluid (skin, blood ) or donates an organ (primarily single kidney
donation, partial donation of liver, lung lobe)
 DECEASED DONOR - deceased 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

7. GRAFT
ACCEPTANCE

8. GRAFT
REJECTION

9. IMMUNOLOGYOF
ALLOGENIC
TRANSPLANTATION
 Allo-antigens elicit both cell mediated and humoral immune response
 Recognition of transplanted cells that are self or foreign is determined by
polymorphic genes that are inherited from both parents and are
expressed co dominantly

10. GENETICS

11. IMMUNOLOGY

12. RECOGNITION
OF
ALLOANTIGENS
 DIRECT RECOGNITION
 Host T cells recognise intact allo MHC molecules on the surface on
donor cell
 Allo MHC molecule + allo peptides
 self MHC + foreign peptide and hence recognise donor tissue as
foreign
 This pathway is dominant pathway
 Leads to direct presentation
 INDIRECT RECOGNITION
 Donor MHC and presented by recipient APC (recognition of
peptides from donor HLA )
 Leads to chronic rejection

15. ACTIVATION OF
ALLOREACTIVE T
CELLSAND
REJECTION OF
ALLOGRAFTS
 Donor APCs migrate to regional lymph nodes and are recognised by
recipient’s T cells
 Alloreactive T cells in the recipient may be activated and they migrate
into graft and cause GRAFT REJECTION

16. EFFECT OF
HLA
MATCHING
 HLA are protein that are located on surface of white blood cells and
other tissue in body
 Three general groups – HLA-A, HLA-B, HLA-DR
 The effect of HLA class I and class II antigen matching on survival of
kidney grafts
 Mismatching of one or two class (HLA-A or HLA-B) antigens has little
effect on graft survival.
 Matching or mismatching of class I antigens has a lesser effect on raft
survival
 When both class I and II antigens are mismatched, rejection is
accelerated

17. ROLE OF
BLOOD
GROUPS
 Blood group antigens are expressed on vascular endothelial cells of
organs.
 Recipient’s natural antibodies may recognize antigens on graft and
cause rejection

18. MECHANISM
OF
REJECTION
 HOST VERSUS GRAFT REJECTION
 Based on histopathological features or time duration of rejection after
transplantation
 1. Hyperacute rejection
 2. Acute rejection
 3. Chronic rejection

19. HYPERACUTE
REJECTION
 Within minutes or hours
 Vascularization is rapidly destroyed
 Recipient has pre existing antibodies in circulation against graft which
could be induced by prior blood transfusion, multiple pregnancies,
prior transplantation
 Antibodies bind with HLAAg on donor endothelial cell
 Ab-Ag complex activate complement system causing migration of
neutrophil leads to inflammation and thrombosis formation in
capillaries, which prevent vascularization
 Kidney is more susceptible to hyperacute rejection

21. ACUTE
REJECTION
 antibodies that usually begin after first week of transplantation if there
is no immunosuppressant therapy
 Vascular and parenchymal injury mediated by T cells
 T cells activates and proliferates
 Massive infiltration of macrophages & lymphocytes
 Tissue destruction
 Graft rejection

22. CHRONIC
REJECTION
 Months to years after acute rejection have subsided
 Characterized by fibrosis and vascular abnormalities with loss of graft
function over a prolonged period
 Occur in most solid organ transplants – heart, kidney, lung and liver
 Invasion and accumulation of white blood cells in artery lead to wall
thickness – Arthrosclerosis
 Cell proliferates
 Blockage or closing of blood vessel – occlusion
 Graft rejection

23. STAGES
 When graft rejection occur in absence of pre existing immunity, it can
be divided in 2 stages
 1. SENSITIZATION PHASE
 Occur shortly after transplantation
 Antigen reactive lymphocyte of recipient proliferate in response to
alloantigens on graft
 2. EFFECTOR STAGE
 Immune destruction of graft takes place through immune system
mediated mechanism

24. GRAFTVS
HOST
REACTION
 In some instances, graft tissue elicits an immune response against host
antigen and that immune response is called graft versus host reaction
 Damage to host cells and host
 When graft tissue has mature t cells , they will attack host tissue leading
to GVHD

25. MECHANISM

26. SIGNSAND
SYMPTOMS
 Pain at site of transplant
 Feeling ill
 Fever
 Weight change
 Swelling
 Decrease urine output
 Drug induced gingival overgrowth
 Lichen planus
 Decreased mouth opening
 Salivary gland dysfunction

27. PALMAR ERYTHEMA
hyperpigmented lichenoid papules
and toxic epidermal necrosis-
hyperpigmented sclerotic plaques

28. MANIFESTATIONS
 STAGE 1 – PRETRANSPLANT
 Mucosal lesions
 Dental decay
 Periodontal infections
 Lymphoma
 Leukemia
 STAGE 2 –EARLY ENGRAFTMENT (10-21 DAYS)
 Mucositis
 Viral infection- HSV
 Fungal infection- candidiasis
 Xerostomia
 Hemorrhage

29.  STAGE 3- EARLY ENGRAFTMENT TO RECOVERY (21-100)
 Mucositis (resolving)
 HSV, VZV
 Candidiasis
 Recurrence of cancer
 STAGE 4- RECOVERY TO IMMUNE RECONSTITUTION (100-
365 DAYS)
 HSV, VZV, CMV
 Candidiasis
 Xerostomia
 Dental/ skeletal growth and development
 STAGE 5- LONG TERM SURVIVAL
 Xerostomia
 Second primary malignancy

30. PREVENTION
OF GRAFT
REJECTION
 BLOOD GROUPING
 CYTOTOXIC ANTIBODY TESTING
 TISSUE MATCHING (HLA MATCHING)
 IMMUNOSUPPRESSIVE DRUGS

31. IMMUNOSUPPRESIVE
DRUGS
 Inhibit or prevent activity of immune system
 Most drugs are nonspecific, resulting in generalised suppression of
response to all antigens
 Given in two phase – initial induction phase involving high dose, later
maintenance phase – involves using drug in long term at lower dose
 Combination of drugs and dosage depend on type of transplant
 If patient experience an episode of acute rejection , drug combination is
subject to change and dosage is likely to increase
 Side effects – alterative drug
 Steroid – most commonly used drugs but have adverse effects

32. Classification
 CORTICOSTEROIDS
 Prednisolone
 Hydrocortisone
 CALCINEURIN INHIBITORS
 Cyclosporine
 Tacrolimus
 ANTIPROLIFERATIVE
 Azathioprine
 Mycophenolic acid
 mTOR INHIBITOR
 Everolimus –

33. CORTICOSTEROIDS
 Reduce inflammation by inhibiting macrophage cytokine secretion
 The major elements blocked are IL-1, IL-6, IL-2, and TNF-α .
 These elements, notably IL-1, are essential for lymphocyte-APC
communication
 Corticosteroids are also able to inhibit cytokine production in
macrophages.
 Inhibits the macrophage phagocytosis and chemotaxis properties.
 Corticosteroids are also potent non-specific anti-inflammatory agents –
 administration results in an acute reduction of circulating lymphocytes
and monocytes.

34. CALCINEURIN
INHIBITORS
 Blocks T cell cytokine production by inhibiting activation of NFAT
transcription factor
 The interaction between IL-2 and the IL-2 Receptor is crucial in the
activation, differentiation, and proliferation of B and T cells.

35. ANTIPROLIFERATIVE
AGENT
 Blocks lymphocyte proliferation by inhibiting guanine nucleotide
synthesis in lymphocytes
 activated lymphocytes are selectively inhibited since they are not allowed
to proliferate once activated.

36. mTOR
INHIBITOR
 blocks the binding of accessory protein raptor

37. CONCLUSION
 The post- transplantation period is hampered by many potential
complications which can lead to morbidity and mortality.
 The most common complications include CsA-induced gingival
enlargement, GVHD, OM, viral infections like HSV infection, and
oropharyngeal candidiasis.
 Among the late complications, secondary malignancies are recognized,
with SCC being the most common.
 These changes emphasize the importance of regular oral screening.
 Most transplant centers conduct a complete oral evaluation before
transplant conditioning.
 The primary responsibilities of a health care professional are prevention
of infections and providing instruction on oral prophylaxis and
hygiene.