TRANSPLANTATION XENOGRAFT (HETEROGRAFT) from animal of
End stage treatment for cancer, autoimmune
diseases, immunodeficiency, organ failure
Transfer of cell, tissue, organs from one part of
body to another in the same individual or from
one person to another
GRAFTING
GRAFT tissue transplanted
TRANSPLANTATION IMMUNOLOGY
Purpose: to substitute or replace a diseased
organ or tissue
Functional success of transplanted tissues and
organs depends on the genetic relatedness of
the donor and the recipients
TYPES OF GRAFT
BASED ON MECHANISM OF TRANSFER
AUTOGRAFT tissue from same body
o Ex. Skin graft, blood vessel, adipose tissue,
rhinoplastic surgery, hemodialysis, bone
marrow transplant
SYNGRAFT (ISOGRAFT)- organs are genetically
identical (separate inner cell mass)
o Ex. Identical/homozygotic twins from a
single egg cell: kidney transplant, bone
marrow transplant
o Chances of rejection are low since the donor
and recipient are genetically similar
ALLOGRAFT (HOMOGRAFT)
o Tissue from genetically distinct individual of
the same species
o Transplant of an organ or tissue from one
individual to another of the same species
with a different genotype
o Ex. Fraternal twins, relatives, mother-
daughter, father-son: most organ
transplants: kidney, heart, lungs, etc.
o Tissue typing, ABO Typing, and HLA
typing are performed before transplanting
tissue to ensure safe transplantation
CADAVERIC DONORS brain-dead or
kakamatay lang
o Most organ transplants
o May be a source of an allograft
another species
o Ex. Mouse-baboon
mouse-human
guinea pig-mouse
baboon-human
- Baboon heart transplanted into a human
- Usually discouraged due to transmission
of viruses
pig-human: closely related species
BASED ON PLACEMENT
ORTHOTOPIC transplant tissue is placed on
the original site where the tissue is
o Ex. Kidney, liver, lung
HETEROTOPIC placement is at different sites
o Ex. Cartilage, ligament, skin graft, adipose,
hair, bone
GROWTH OF TISSUE
HOMOSTATIC no occurrence of growth after
transplantation
HOMOVITAL if growth happens upon
transplantation
PRIVILEGED SITE where you could transplant
without fear of rejection
o Highly avascular
o Away from lymphatic circulation
o Ex. Anterior chamber of the eye
PRIVILEGED ORGAN
o Equipped with mechanism which will not
allow it to combine with other substances
o Ex.
- Testicles if nadamage, contents will
leak, it will be considered foreign once
detected by immune cells; Blood-testes
barrier
- Uterus acceptance due to compatibility
in HLA Class I (HLA-G); endometrial layer
- Brain blood-brain barrier
IMMUNOGENIC TISSUES
Most immunogenic tissues = higher risk of
rejection
o Ex. Bone marrow, Skin, Islet of Langerhans,
Heart, Kidneys, Liver, Bone, Xenogeneic valve
replacement
o Bone - Apparently modify and decrease
surface antigens (ethylene oxide or gamma
radiation)
o Kidney ABO and HLA
Cadaveric transplantation
number of mismatches is zero or one
o Liver, Heart and Lungs Problem: Difficulty
in detecting rejection episodes
o Heart transplanted within 4 hours
prospective matching
DNA typing
Donors and recipients: ABO and size of the
organs
o Pancreas Islet cells: life-enhancing
ABO blood grouping
tissue crossmatching
matching of HLA-DR Antigens
o Bone Marrow HLA: more crucial;
regenerate replacement marrow within 8
weeks
high doses of chemotherapy or radiation to
prevent radiation, destroy any residual
cancer cells, and provide space for the new
marrow to grow
Least immunogenic tissues = avascular (
o ex. Cornea Does not evoke rejection; tissue
does not come in contact with the
immunologic system
TYPES OF TISSUE REJECTION
HYPERACUTE REJECTION
o Within minutes to hours
o Mechanism: Humoral
o Vascularization rapidly destroyed
o Main mediator: individual has pre-formed
cytotoxic antibodies to donor antigen
o Binding of preformed antibodies to the
alloantigens activates the complement
cascade and clotting mechanisms and leads
to thrombus formation
o After the tissue is transplanted, as soon as
the vascular connection started between the
graft and the circulation, the temperature of
the patient immediately starts to decrease
o Chills, fever, change in color of graft
o Common in:
a) Already gone through more than one
transfusion or transplantation
- Other antigens introduced padami
nang padami ang antibodies produced
na possible na missed out sa panel
testing
b) Multiple birth (Multiparous women):
more Ag = more Ab
ACUTE REJECTION
o Primary days after rejection
o Secondary days after rejection
o Cell-mediated (ADCC)
o Development of allogenic reaction to donor
antigen
o Inflammatory reactions, discoloration,
formation of necrosis on grafted tissue
o Characterized by parenchymal and vascular
injury
o CD8 cells likely mediate cytotoxic reactions
to foreign MHC-expressing cells
o CD4 cells likely produce cytokines and
induce delayed-type hypersensitivity (DTH)
reactions
CHRONIC REJECTION
o Weeks to months to years
o Mechanism: Cellular
o Fibrosis fibrous tissue growth
o Scarring
o Mediator: Non-HLA components
Complement components (MHC Class III)
Disturbance of host/graft tolerance
o Results from a process of graft
arteriosclerosis characterized by progressive
fibrosis and scarring with narrowing of the
vessel lumen due to proliferation of smooth
muscle cells
o Factors: prolonged cold ischemia,
reperfusion, acute rejection episodes, toxicity
from immunosuppressive drugs
HLA-DR Major transplantation barrier
PROLONGING GRAFT SURVIVAL:
IMMUNOSUPPRESSIVE DRUGS
CORTICOSTEROIDS potent anti-inflammatory
and immunosuppressive agents used for
immunosuppression maintenance
o Treatment of acute rejection episodes
o Steroids block production and secretion of
cytokines, inflammatory mediators,
chemoattractants, and adhesion molecules
o May cause hypertension and diabetes
mellitus

ANTI-METABOLITE/ANTI-PROLIFERATIVE
AGENTS interfere with maturation of
lymphocytes and kill proliferating cells
o Azathioprine
o Mycophenolate mofetil

CALCINEURIN INHIBITORS
o Cyclosporine and FK-506 (tacrolimus)- block
signal transduction in T lymphocytes,
resulting in impairment in cytokine synthesis,
including IL-2, 3, 4 and interferon-gamma
o Rapamycin (sirolimus)- inhibits T-cell
proliferation by binding to specific
intracellular proteins

MONOCLONAL ANTIBODIES - bind to cell

surface molecules on lymphocytes; used as
induction agents and to treat severe rejection
episodes
o OKT3- mouse monoclonal antibody that
binds to CD3 receptor on human
lymphocytes
o Basiliximab and dacluzimab- bind the CD25
(IL-2 receptor), interfering IL-2 mediated T
cell activation
o Alemtuzumab- for induction therapy

POLYCLONAL ANTIBODIES - deplete

lymphocytes from the circulation
o Thymoglobulin- antithymocyte antibody
prepared in rabbits
o ATGAM- polyclonal antiserum prepared
from immunization of horses