Organ Transplantation
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Transcript of Organ Transplantation
Assoc. Prof. Ma. Jennifer R. Tiburcio, MSMT
Department of Med Tech
UST Faculty of Pharmacy
Grafting Transfer of cells One part of the body to another One individual to another
Transferred material (graft)
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
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
Most immunogenic
Bone marrow
Skin
Islet of langerhans
Heart
Transplant TissueTransplant Tissue
Kidneys
Liver
Bone
Xenogeneic valve replacement
Least immunogenic
Cornea
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
CornealDoes not evoke rejection
Tissue does not come in contact with the immunologic system
BoneProvide mechanical function
and supportEthylene oxide or gamma radiation
Kidney
ABO & HLACadaveric transplantation
Number of mismatches is zero or one
Liver, heart & Lungs
Problem – difficulty in detecting rejection episodes
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
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
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
Host- Versus- Graft Reaction
Graft- Versus- Host Reaction
HOST RESPONSE TO HOST RESPONSE TO TRANSPLANTATIONTRANSPLANTATION
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
Graft- Versus- Host Graft- Versus- Host ReactionReaction
Graft- Versus- Host Graft- Versus- Host ReactionReaction
Common manifestations:– Diarrhea– Erythema– Weight loss– Malaise– Fever– Joint pains– Death
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.
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’
Mixed leukocyte reactionMixed leukocyte reaction
Detects the degree of immune cellular stimulation of the recipient’s T lymphocytes by donor cells.
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.
Antigen Non-specific
Drugs: Azathioprine
Steroids
Cyclosporine
Anti-lymphocyte globulin
Radiation
Immunosuppressive TreatmentsImmunosuppressive Treatments
Antigen specificNeonatal tolerization
Enhancing (anti-allogeneic) antibodiesAnti-idiotype antibodies to receptors on T
cellBlood transfusion in human kidney
transplant