Download - Organ Transplantation
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Assoc. Prof. Ma. Jennifer R. Tiburcio, MSMT
Department of Med Tech
UST Faculty of Pharmacy
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Grafting Transfer of cells One part of the body to another One individual to another
Transferred material (graft)
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TERM SOURCE OF TISSUE
EXAMPLES
Autograft Tissue is from the recipient
Autologous skin grafting, bone marrow transplants
Syngraft (Isograft)
Tissue from a genetically identical individual, i.e. identical twin
Kidney transplant, bone marrow transplant
Allograft (Homograft)
Tissue from a genetically distinct individual of the same species
Most organ transplants: kidney, heart, lungs, etc.
Xenograft (Heterograft)
Material from an animal of a different species
Baboon heart transplanted into a human
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Physical Placement1. Orthotopic – same place2. Heterotropic – different site
Growth Properties of graft1. Homostatic – no occurrence of growth
of the transplanted graft 2. Homovital – occurrence of tissue growth
after transplantation
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Most immunogenic
Bone marrow
Skin
Islet of langerhans
Heart
Transplant TissueTransplant Tissue
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Kidneys
Liver
Bone
Xenogeneic valve replacement
Least immunogenic
Cornea
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TYPE OF TISSUE
TIME OF TISSUE
DAMAGE
MECHANISM CAUSE
Hyperacute W/in minutes Humoral Preformed cytotoxic antibodies to donor antigen
Accelerated 2 to 5 days Cellular Previous sensitization to donor antigen
Acute 7 to 21 days Cellular (ADCC) Development of allogeneic rxn to donor antigen
Chronic Later than 3 months
Cellular Disturbance of host/graft tolerance
Immunopatholo-gic damage to the new organ
Later than 3 months
1. immune complex disorder2. complex formation w/ soluble antigen
Immunopathologic mechanisms rela-ted to circumstan- ces necessitating transplant
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CornealDoes not evoke rejection
Tissue does not come in contact with the immunologic system
BoneProvide mechanical function
and supportEthylene oxide or gamma radiation
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Kidney
ABO & HLACadaveric transplantation
Number of mismatches is zero or one
Liver, heart & Lungs
Problem – difficulty in detecting rejection episodes
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Heart
Transplanted within 4 hrsProspective matching
DNA typingDonors & recipients –ABO &
size of the organs
Pancreas
Islet cells – life-enhancingABO blood groupingTissue crossmatching
Matching of HLA-DR antignes
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HLA – more crucialRegenerate replacement marrow w/in 8 weeks
High doses of chemotherapy or radiation- to prevent rejection
Destroy any residual cancer cellsProvide space for the new marrow to grow
Bone marrow
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Graft-versus-host Graft-versus-host (GVH disease)(GVH disease)
Occurs when grafted immunocompetent cells from a donor mount an IR against the host tissues
Matching of the HLA-A & B and HLA-DwUse of methotrexate & cyclosporin has greatly
reduced the occurrence of this phenomenon
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Host- Versus- Graft Reaction
Graft- Versus- Host Reaction
HOST RESPONSE TO HOST RESPONSE TO TRANSPLANTATIONTRANSPLANTATION
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In Organ Transplantation: foreign HLA molecules of the graft serve as ligands (targets) for T cell receptors in the recipient, initiating an inflammatory response that leads to loss of graft function.
= GRAFT REJECTIONGRAFT REJECTION
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Graft- Versus- Host Graft- Versus- Host ReactionReaction
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Graft- Versus- Host Graft- Versus- Host ReactionReaction
Common manifestations:– Diarrhea– Erythema– Weight loss– Malaise– Fever– Joint pains– Death
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Lymphocytotoxicity TestLymphocytotoxicity Test
Used for the serological detection of MHC class 1 & class II antigens.
Once a donor has been selected, the match is confirmed by using donor’s cell &recipients serum in a repeat lymphocytotoxicity test.
If the patient’s serum is cytotoxic or the donor’s cells the transplant is not performed.
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Patients lymphocytes
incubateReagent Antibody
Add C’
Tryptan bluedye
Live cells take up no dye=Negative for that HLA Ag
Dead cells take up dye= positive for that HLA antigen
c
c
incubate
+ C’
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Mixed leukocyte reactionMixed leukocyte reaction
Detects the degree of immune cellular stimulation of the recipient’s T lymphocytes by donor cells.
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DonorLymphoctes +Recipients lymphocytes Tritiated
Day 5 Count radioactivity in cells
Lymphocyte are isolated from the whole blood of both the donor &the recipient using Ficoll-Hypaque centrifugation.The lymphocytes are incubated together at 37degrees Celsius for 5 days.
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Antigen Non-specific
Drugs: Azathioprine
Steroids
Cyclosporine
Anti-lymphocyte globulin
Radiation
Immunosuppressive TreatmentsImmunosuppressive Treatments
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Antigen specificNeonatal tolerization
Enhancing (anti-allogeneic) antibodiesAnti-idiotype antibodies to receptors on T
cellBlood transfusion in human kidney
transplant
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