Immunology of transplantation
Types of transplantation
• Autotransplantation –within one organism
• Allotransplantation- between one species
• Xenotransplantation- between two
different species
Success rate of transplantation in humans
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© 2005 Elsevier
Polymorphism of HLA antigens
Co-dominant expression of HLA genes
Effect of HLA-identity on kidney graft survival
Cross match test
• Used for detection of recipient´s antibodies
against donor´s antigens (mainly HLA
antigens)
• Donor´s leukocytes + patient´s plasma
• Positivite – antibodies bind to leukocytes –
can be detected e.g. by flow cytometry
• Positivity contraindicates transplantation
Types of graft rejection
• Hyperacute - minutes to hours after
transplantation. Caused by pre-formed
recipient antibodies against HLA antigens of
the donor. Irreversible.
• Acute -several days to months after
transplantation. Mainly T-cell mediated.
Usually reversible by aggressive
immunosuppression.
• Chronic - years after transplantation.
Continuous decrease in graft function.
Irreversible. Mechanism unknown.
The most frequent types of organ
transplantation
• Heart
• Kidney
• Liver
• Lungs
• Pancreas
• Cornea
Heamatopoietic stem cells
transplantation
• Indications: malignancies, bone marrow
failure, primary immunodeficiencies.
• “Whole“ bone marrow or separated CD34+
cells can be used.
• The most significant complication: graftversus
host reaction (GVHR).
• Optimal HLA-matched donor is required.
Graft-versus host reaction (GVHR)
• Immunological reaction of transplanted T-cells
against recipients (HLA) antigens.
• Skin, liver, intestine predominantly affected.
• Milder forms can be treated by
immunosuppression, severe forms may be fatal.
• Can be induced by transfusion of non-irradiated
blood to immunodeficient patients (primary
immunodeficiencies, leukemia…).
Systemic Immunosuppression
• High-dose steroids
• Purine antagonists: Azathioprin
• Alkylating agents: Cyclophosphamide
• Anti-pholates: Methotrexate
• Calcineurin antagonists: Cyclosporine A,
Rapamycin, Tacrolymus
• Block of purins synthesis: Mycophenolate
• Monoclonal antibodies: anti-CD3, anti-CD20,
anti-CD54