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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

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

ISOGRAFTfrom genetically identical individual

ALLOGRAFTfrom genetically different individual of the same species

XENOGRAFTindividual from one species to other species

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

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 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

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

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Indirect allorecognition

More T cells are activated in the immune response to graft than in an infection

APC

TTTT

T

TRANSPLANTATION

APC

T

INFECTION

selfpeptide

foreignpeptide

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

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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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

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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

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)

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.

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