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Transcript of 1 Transplantation therapy for terminal organ failure or tissue damage by transfer of healthy organ...
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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...
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Graft
AUTOGRAFT skin
ISOGRAFTfrom genetically identical individual
ALLOGRAFTfrom genetically different individual of the same species
XENOGRAFTindividual from one species to other species
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Transplantation
• Autotransplantation
• Isotransplantation
• Allotransplantation
• Xenotransplantation
no immune response or graft rejection
immune response and graft rejection
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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
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WHAT ARE TRANSPLANTATION ANTIGENS?
Relative degree ofAntigens polymorphism------------------------------------------------------------------------------1) ABO blood group
2) Major histocompatibility complex (MHC)
3) Minor histocompatibility antigens (non-MHC antigens)
4) Xenoantigens
Limited
Very high
Limited
Extremely high
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Direct allorecognition
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© 2005 Elsevier
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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
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© 2005 Elsevier
Indirect allorecognition
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More T cells are activated in the immune response to graft than in an infection
APC
TTTT
T
TRANSPLANTATION
APC
T
INFECTION
selfpeptide
foreignpeptide
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Elimination of graft cells
CYTOKINES(IFN-γ)
free radicals
MF
DC
CTL
Th
MHC II
MHC I
CD4
CD8
activation and proliferation
activation and proliferation
B
At
Complement activation
NK
Injury mechanisms during graft rejection
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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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© 2005 Elsevier
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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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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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© 2005 Elsevier
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Bone marrow transplantation
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Graft-versus-host disease – GVHDin bone marrow transplantation
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Testing for donor-recipient compatibility
• ABO blood typing• Tissue typing: HLA matching• Screening for the presence of pre-
formed 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)
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alloantigens and xenoantigensj.In bone marrow transplantation10.
donor’s T cells react to recipient MHC molecules
i.In prevention and treatment of graft rejection we use
9.
processes and presents alloantigens h.Allograft rejection due to pre-formed recipient’s Abs is called
8.
imunosuppressive therapyg.Indirect alloantigen recognition happen when recipient’s APC
7.
xenotransplantationf.Direct alloantigen recognition means that
6.
MHC moleculese.Allo-MHC molecules could be recognized by
5.
allotransplantationd.Main alloantigens during rejection are4.
recipient’s T cells recognize allo-MHC molekule on donor’s cells
c.Antigens recognized during rejection are
3.
direct and indirect recognitionb.Transplantation from an individual from different species is called
2.
hyperacute rejectiona.Transplantation of tissue or organ from gennetically different individual from the same species is called
1.
1.____ 2.____ 3.____ 4.____ 5.____ 6.____ 7.____ 8.____ 9.____ 10.___d f j e b c h a g i