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overview
• History of Kidney transplantation
• Immunologic Principles of Kidney
Transplantation
• Evaluation of Donor and Recipient
• Kidney Transplant Surgery
• Immunosuppressive Therapy
• Complications of Kidney Transplantation
History of Kidney transplantation
Dr. Joseph Murray and the medical team at Boston's Peter Bent Brigham Hospital
perform the first successful long-term organ transplant, Dec. 23, 1954
History of Transplantation
Ten months after the transplant, Ronald Herrick (left) and his identical twin
Richard toast their good health.
History of Kidney Transplantation in
Bulgaria
Rejection
Main groups of cells participating in
the immune response
• APC – dendrite cells, macrophages, B-
lymphocytes – activate T-Lymphocytes
• T-lymphocytes – CD 4/+/, CD8/+/
• B-Lymphocytes – antibody production,
presence of specific B- Cell Receptor
Stages of immune response
• APC – activation
• T-Lymphocyte activation
• B-lymphocyte activation
• Damage of target organ /transplanted
kidney
• End of the immune response
The MHC
• 3 gene regions - MHCI, MHC II, MHC III
• MHC molecules – class I and class II –
involved in rejection
• Importance – present the antigen to the T-
lymphocytes
• Encoding – HLA – A,B,C/HLA- DR, DP,
DQ
• Expression of the MHC molecules
Structure of MHC molecules
Activation of APC
• Detection of donor
peptides
• Migration to
secondary lymph
organs
• Presenting the
peptide to T-
lymphocytes
HLA match/mismatch
• HLA formula donor • HLA formula recipient
HLA 1 13 HLA 1 14
A
HLA 1 13 A
A
HLA 2 11 HLA 5 11
HLA
B 2 11 B
B
HLA 15 23 HLA 15 28
HLA 15 23
DR DR
DR
HLA
HLA 0202 06 06 HLA 02 06
DQ
DQ DQ
mismatches matches
Activation of T-lymphocytes – T-cell
receptor
Activation of T-lymphocytes –
signal 1
Activation of T-lymphocytes –
signal 1
Activation of CD3
NFAT activation
Signal 2 – amplifies the immune
response
Signal 3 – proliferation of activated
cells
NFAT and NFκB
activation
Increased expression
of ILR-2 and IL2
M-TOR activation
Activated T-
Lymphocytes
proliferation
Effector functions of activated T-
cells
• Peptide molecule
• CsA levels are
monitored
• Side effects
• Dose 5mg/kg
Calcineurin inhibitors – Tacrolimus
/FK 506/
• Macrolide antibiotic
• Binds to FKBP
• Inhibits calcineurin
• Stronger
immunosuppressant
than CsA
• Dose 0.1mg/kg
M-TOR Inhibitors
• Binds to FKBP
• Blocks proliferation
of activated T-
lymphocytes
• Preparations –
Rapamune,
Everolimus
• Drug levels
monitored
Protein molecules
• Antibodies against
Lymphocytes/ Ly-
receptors
• Polyclonal/monoclonal
• Animal – horse,
rabbit,
murine/humanized
Polyclonal AB
• ATG – Thymoglobulin
• Rabbit/horse Ab
• ↓Ly count
• Indications
• Side effects – Neo, infections
Monoclonal AB – anti CD25
• CD 25 = IL-2Rα
• Humanized Ab
• Preparations –
Basiliximab,
Diclazumab
• No reduction in Ly -
count
Monoclonal AB
• Anti-CD3 – OKT3
murine antibodies
• Anti CD20 Rituximab
↓B-Ly proliferation
• Anti CD 52 –
Campath
• Anti CD40L – inhibit
signal 2
Fusion proteins CTLA4-IgG
• Laparoscopic techniques
• Open incision
Transplantation procedure
• Recurrent disease
• CsA – nephrotoxicity
• De novo glomerulonephritits
Infections
• Diabetes mellitus
• CV disease
• Osteoporosis
• Dyslipidaemia
• Malignancies
Thank You for Your Attention!!!