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
Autograft

SOURCE OF TISSUE Tissue is from the recipient Tissue from a genetically identical individual, i.e. identical twin Tissue from a genetically distinct individual of the same species

EXAMPLES Autologous skin grafting, bone marrow transplants Kidney transplant, bone marrow transplant

Syngraft (Isograft)

Allograft (Homograft)

Most organ transplants: kidney, heart, lungs, etc.

Xenograft (Heterograft)

Material from an animal of a different species

Baboon heart transplanted into a human

Physical Placement 1. Orthotopic same place 2. Heterotropic different site Growth Properties of graft 1. Homostatic no occurrence of growth of the transplanted graft 2. Homovital occurrence of tissue growth after transplantation

Transplant Tissue
Most

immunogenic Bone marrow Skin Islet of langerhans Heart

Kidneys Liver Bone Xenogeneic valve replacement

Least

immunogenic Cornea

TYPE OF TISSUE
Hyperacute

TIME OF TISSUE DAMAGE W/in minutes

MECHANISM

CAUSE

Humoral

Accelerated

2 to 5 days

Cellular

Preformed cytotoxic antibodies to donor antigen Previous sensitization to donor antigen

Acute

7 to 21 days

Cellular (ADCC)

Development of allogeneic rxn to donor antigen

Disturbance of host/graft tolerance
Immunopathologic

Chronic

Later than 3 months Later than 3 months

Cellular

Immunopathologic damage to the new organ

1. immune complex disorder 2. complex formation w/

mechanisms related to circumstances necessitating transplant

Corneal

Does not evoke rejection Tissue does not come in contact with the immunologic system

Bone

Provide mechanical function and support Ethylene oxide or gamma radiation

Kidney

ABO & HLA Cadaveric transplantation Number of mismatches is zero or one

Liver, heart & Lungs

Problem difficulty in detecting rejection episodes

Heart

Transplanted within 4 hrs Prospective matching DNA typing Donors & recipients ABO & size of the organs

Pancreas

Islet cells life-enhancing ABO blood grouping Tissue crossmatching Matching of HLA-DR antignes

Bone marrow

HLA more crucial Regenerate replacement marrow w/in 8 weeks High doses of chemotherapy or radiationto prevent rejection Destroy any residual cancer cells Provide space for the new marrow to grow

Graft-versus-host (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-Dw Use of methotrexate & cyclosporin has greatly reduced the occurrence of this phenomenon

HOST RESPONSE TO TRANSPLANTATION

Host- Versus- Graft Reaction Graft- Versus- Host Reaction

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 REJECTION

Graft- Versus- Host Reaction

Graft- Versus- Host Reaction

Common manifestations:
Diarrhea
Erythema Weight loss Malaise Fever Joint pains Death

Lymphocytotoxicity 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 donors cell &recipients serum in a repeat lymphocytotoxicity test. If the patients serum is cytotoxic or the donors cells the transplant is not performed.

Patients lymphocytes
incubate Reagent Antibody

Add C
incubate c Tryptan bluedye c Dead cells take up dye= positive for that HLA antigen
+ C

Live cells take up no dye= Negative for that HLA Ag

Mixed leukocyte reaction

Detects the degree of immune cellular stimulation of the recipients 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.

Immunosuppressive Treatments
Antigen

Non-specific
Drugs: Azathioprine Steroids Cyclosporine Anti-lymphocyte globulin Radiation

 Antigen

specific

Neonatal tolerization Enhancing (anti-allogeneic) antibodies Anti-idiotype antibodies to receptors on T cell Blood transfusion in human kidney transplant