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Transplantation
• therapy for terminal organ failure or tissue
damage by transfer of healthy organ or tissue
(graft)
• donor - the individual who provides the
graft is called the and is called either the
• recipient or the host - the individual who
receives the graft
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Common transplants
Organs
heart, lungs, kidney,liver, pancreas, small intestine...
Tissues & cells
cornea, skin, Langerhan’s islets, bone marrow, blood
transfusion, blood vessels, bone, heart valve...
Graft
AUTOGRAFT skin
ISOGRAFT
from genetically identical individual
ALLOGRAFT
from genetically different individual of the same species
XENOGRAFT
individual from one species to other species
Transplantation
• Autotransplantation
• Isotransplantation
• Allotransplantation
• Xenotransplantation
no immune response
or graft rejection
immune response
and graft rejection
MHC differences induce immune response
and allograft rejection
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Alloantigens (histocompatibility antigens)
graft molecules recognized as foreign and causing
rejection
Alloreactive lymphocytes, alloreactive Abs
lymphocytes and Abs reacting against alloantigens
WHAT ARE TRANSPLANTATION
ANTIGENS?
Relative degree of
Antigens
polymorphism
-----------------------------------------------------------------------------1) ABO blood group
Limited
2) Major histocompatibility
complex (MHC)
Very high
3) Minor histocompatibility
antigens (non-MHC antigens)
Limited
4) Xenoantigens
Extremely high
Direct allorecognition
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Graft rejection after direct immune recognition
Langerhansove ćelije
kožnog kalema
Migracija u lokalni LČ
i aktivacija
efektorskih T-ćelija
Efektorske T-ćelije
odlaze u kalem
Reakcija odbacivanja
Indirect allorecognition
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More T cells are activated in the immune response
to graft than in an infection
INFECTION
TRANSPLANTATION
T
foreign
peptide
self
peptide
APC
T
T
T
APC
T
T
Injury mechanisms during graft rejection
CYTOKINES
activation and
proliferation
Th
(IFN-γ)
CD4
B
NK
MF
CTL
CD8
At
free
radicals
activation and
proliferation
Elimination of graft cells
Complement activation
DC
Allograft rejection
Hyperacute (few hours)
Pre-formed Abs to blood type Ags and MHC
molecules
Acute (few days/weeks)
Chronic (several months to years)
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Allograft rejection
Hyperacute (few hours)
Pre-formed Abs to blood type Ags and MHC
molecules
Acute (few days/weeks)
Vascular (Abs to MHC molecules)
Cellular (T cells and macrophages)
Chronic (several months to years)
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© 2005 Elsevier
Allograft rejection
Hyperacute (few hours)
Pre-formed Abs to blood type Ags and MHC
molecules
Acute (few days/weeks)
Vascular (Abs to MHC molecules)
Cellular (T cells and macrophages)
Chronic (several months to years)
Tissue fibrosis and blood vessel walls thickening
(TGF-β)
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Bone marrow transplantation
Graft-versus-host disease – GVHD
in bone marrow transplantation
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Testing for donor-recipient
compatibility
• ABO blood typing
• Tissue typing: HLA matching
• Screening for the presence of preformed antibodies
• Cross-matching
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Prevention and treatment of
allograft rejection
Immunosuppressive drugs
- Corticosteroids (anti-inflammatory effect)
-Cyclosporin A, Tacrolimus... (block T cell
activation and cytokine production)
-Mycophenolate mofetil (blocks lymphocyte
proliferation by blocking guanine synthesis)
-Rapamycin (blocks lymphocyte proliferation
by inhibiting IL-2 signalling)
- Abs to TCR (CD3) and co-stimulatory
molecules (CTLA4)
1. Transplantation of tissue or organ
from gennetically different individual
from the same species is called
2. Transplantation from an individual
from different species is called
3. Antigens recognized during rejection
are
4. Main alloantigens during rejection are
a. hyperacute rejection
5. Allo-MHC molecules could be
recognized by
6. Direct alloantigen recognition means
that
7. Indirect alloantigen recognition
happen when recipient’s APC
e. MHC molecules
8. Allograft rejection due to pre-formed
recipient’s Abs is called
h. processes and presents alloantigens
9. In prevention and treatment of graft
rejection we use
10. In bone marrow transplantation
d
1.____
f
2.____
j
3.____
e
4.____
b
5.____
b. direct and indirect recognition
c. recipient’s T cells recognize allo-MHC
molekule on donor’s cells
d. allotransplantation
f. xenotransplantation
g. imunosuppressive therapy
i. donor’s T cells react to recipient MHC
molecules
j. alloantigens and xenoantigens
c
6.____
h
7.____
a
8.____
g
9.____
i
10.___