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Immunology of transplantation

Veterinary ImmunologyVeterinary education, 3rd year

24/04/2019

Transplantation

Organ transplantation: is a medical procedure in which an organ is removed from one body and placed in the body of a recipient, to replace a damaged or missing organ. The donor and recipient may be at the same location, or organs may be transported from a (donor) site to another location (recipient).Rejection: an immune reaction against grafted tissue that resultsin failure of the graft to survive.Graft: transplantatum

Classification of Grafts

Autograft: own tissue (blood, bone marrow, skin)Syngraft, isograft: genetically identical individuals (inbred animals, twins)Allograft: different individuals of the same species (7-10 days)Xenograft: different species (pig liver to humans) (10-20 minutes)

Frequency of Organ Transplatation

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Transplantation

High demand for organs and tissues in human medicine • Split technique, not complete organs

– One from double organs (kidney)– Langerhans islets– One lobe of liver

• Artificial organs (exotransplants)• In vitro growing of organs• Xenotransplants

– Transgenic minipig skin, heart valve – Changed after 10-15 years

Xenotransplants to Humans

xeno = foreign (greek)

History• 1895: sheep pancreas – death• 1905: rabbit kidney – 16 days• 1906: pig and goat kidneys – death

primate kidney – 32 hours• 1923: sheep kidney – 9 days• 1964-1995: approximately 50 primate organs transplanted into humans

– Survival: 1 day-4 months– 1 exception: baboon bone marrow (1995-2007)

Xenoreactive antibodies in humans• Induced by bacteria in the gut after birth• Cross reacts with gal1α Atg of the endothelium• Atg not present in non-vascularized organs (heart valve)

Xenotransplantatio

• Based on the ever increasing shortage of suitable donor organs, the research of xenotransplantation grew more intensive than ever before

• The problems associated with xenotransplantation can be divided into four categories 1. Immunological2. Physiological3. Infectious-microbiological4. Ethical

Donor Animal

Primates• Advantages

– Immunological closeness– Physiological relatedness– Phylogenetically closest to humans

• Disadvantage– Endangered species– Difficult to propagate– Organized social societies– Self-conscious – Keeping in aseptic conditions not solved– Genetic manipulation techniques not developed– Size of organs– Chances of zoonotic infections

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Donor Animal Donor Animal

Is it unimaginable? Xenotransplants to Humans

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Not Rejected Tissues

• Cornea, brain: no direct connection to the lymphoid system• Highly differentiated tissues: no MHC expression (heart valve)• Sperm: no MHC Atg, immunosuppressive chemicals• Embryo: 50% allograft, no MHC expression until implantation• Immunosuppressiv substances produced by the fetus– Prostaglandin– α-fetoprotein– β2 microglobulin

• Trophoblast cells– No MHCI vagy II– MHCI-like proteins (to fool NK)

• Blocking antibodies (covering the placenta)

Host versus Graft

Rejection• Hyperacute: minutes

– Allografts: ongoing active response– Xenografts: Ab, complement

• Acute: 2-5 days– Secondary immune response

• Late acute: 7-21 days– Primary immune response– Delayed type hypersensitivity (DTH)

• Chronic– After immunosuppression– DTH

Graft Rejection Usual Mechanism of Rejection

• Soluble MHC Atg carried to lymph nodes

• Activation (and chemotaxis)– Macrophages– NK, T and B

• Cytotoxic reactions– Tc, NK

• Ab production– ADCC, Cpl activation

• Cell and tissue damage

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Hyperacute Rejection Acute and Late Acute Rejection

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Chronic Rejection Graft versus Host

• Graft Versus Host (GVH) reaction– In immunosuppressed recipients– Bone marrow transplants– Skin lesions, anaemia, diarrhoea, icterus

• MHC and mHC antigens– mHC: any polimorph Atg– Advance rejection with MHC

• Tc and NK cells• Th and B cells

• Atg presentation– Direct: graft cell MHCI and II– Indirect: degraded graft components (Atg) presented by host MHC

Outcome of TransplantationDepends on

1. MHC, mHC compatibility• MLR (mixed lymphocyte reaction)• Serology• PCR

2. Immunosupression of the recipient

3. Graft preparation• Removal of MHC or MHC rich cells

HaematopoeticStem Cell

Transplantation

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Thank you foryour attention!