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