lecture 11 tpl immunology
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8/13/2019 Lecture 11 Tpl Immunology
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Transplantation Immunology
Lucian P. Jiga, MD, PhD
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3rd century, AD
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9th century, AD
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1818 - 1st successful blood transfusion
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1831 - Frankenstein published
1st documentation for use ............................... of cadaver parts/organs
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20th century - Tx becomes realityEduard K. Zirm - 1905 - 1st cornea Tx
A. Carrel - 1902-1908 - vascular suture
P. Medawar & FM. Burnet - 1940 - acquired immune tolerance
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Acquired immunity
Strain A - Donor
Strain B - Recipient
Strain B - Recipient
Strain B - Recipient
10 days
3 days
3 days
ADAPTIVITY
MEMORY
LYMPHOCYTES
Acute rejection - 1set kinetics
Hyperacute rejection - 2 set kinetics
Hyperacute rejection - 2 set kinetics
10 days
Acute rejection - 1set kinetics
SPECIFICITY
Strain C - Donor
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Immunological tolerance
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Immunological tolerance
SKIN GRAFT
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Immunological tolerance
ACCEPTANCE
SKIN GRAFT
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Immunological tolerance
SKIN GRAFT
ACCEPTANCE
SKIN GRAFT
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Immunological tolerance
SKIN GRAFT
ACCEPTANCE
REJECTION
SKIN GRAFT
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Immunological tolerance
SKIN GRAFT
ACCEPTANCE
REJECTION
CELL PRECONDITIONING
SKIN GRAFT
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Immunological tolerance
SKIN GRAFT
SKIN GRAFT
ACCEPTANCE
REJECTION
CELL PRECONDITIONING
SKIN GRAFT
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Immunological tolerance
SKIN GRAFT
SKIN GRAFT
ACCEPTANCE
REJECTION
ACCEPTANCE
CELL PRECONDITIONING
SKIN GRAFT
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...the rest is history
J. Hardy - 1963
T. Starzl - 1967
C. Barnard - 1967
AZA & CyA - 1962 - 1970 (1983 - FDA approved)
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...the rest is history
1984 - Baby Fae receives a baboon hear t
1992 - 1st baboon to human liver Tx
1993 - 2nd baboon to human liver Tx
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...the rest is history
1998 - 1st hand transplant
2005 - 1st part-face Tx 2011 - 1st full-face Tx in USA
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...so what happens after Tx
1. Alloantigen recognition
2. T-cell activation
3. Allograft destruction
In the absence of immunosuppression
ACUTE REJECTION
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Alloantigen recognition
Tx between the same inbred strain will never be rejected
Tx between individuals of different inbred strains will almost always be rejected
Offspring of 2 different inbred strains (F1 hybrid) will never reject grafts from either parents
an F1-derived graft will almost always be rejected by either parents
polymorphic codominantly expressed molecules................are responsible for rejection
Polymorphism= graft antigens differ among individuals/species
Codominance= (AxB)F1 accepts A-B parental grafts
Codominance= A or B parents will reject (AxB)F1 grafts
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Alloantigen recognition
MHC molecules are responsible for acute rejection after Tx
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Alloantigen recognition
MHC molecules are responsible for acute rejection after Tx
Graft-infiltrating APCs
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Alloantigen recognition
MHC molecules are responsible for acute rejection after Tx
Graft-infiltrating APCs
Recipient APCs
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Alloreactive T cell activation
http://www-ermm.cbcu.cam.ac.uk
remember MHC & Antigen processing course!!
http://www-ermm.cbcu.cam.ac.uk/http://www-ermm.cbcu.cam.ac.uk/ -
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types of rejection
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types of rejection
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types of rejection
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The fate of allografts
www.ctstransplant.org
http://www.ctstransplant/http://www.ctstransplant/ -
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The fate of allografts
n = 131985
www.ctstransplant.org
http://www.ctstransplant/http://www.ctstransplant/ -
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The fate of allografts
n = 131985
www.ctstransplant.org
http://www.ctstransplant/http://www.ctstransplant/ -
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The fate of allografts
www.ctstransplant.org
http://www.ctstransplant/http://www.ctstransplant/ -
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The fate of allografts
www.ctstransplant.org
http://www.ctstransplant/http://www.ctstransplant/ -
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The fate of allografts
www.ctstransplant.org
http://www.ctstransplant/http://www.ctstransplant/ -
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The fate of allografts
www.ctstransplant.org
http://www.ctstransplant/http://www.ctstransplant/ -
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The fate of allografts
www.ctstransplant.org
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Ways to induce tolerance
CD80/86 (B7.1/
B7.2)
CD28
Janeway CA et al - Immunobiology, 5th edition
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Ways to induce tolerance
CD80/86 (B7.1/
B7.2)
CD28
TransgenicIDO, TGFb, IL10, CTLA4, PD-1
Selective OGN
Immature DCs
VDR/1.25-(OH)(2)D3
Janeway CA et al - Immunobiology, 5th edition
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Ways to induce tolerance
CD80/86 (B7.1/
B7.2)
CD28
TransgenicIDO, TGFb, IL10, CTLA4, PD-1
Selective OGN
Immature DCs
VDR/1.25-(OH)(2)D3
FoxP3 Tregs
TRP depletion
HAA, Ky, 3-OH-Ky
costim. blockade
Janeway CA et al - Immunobiology, 5th edition
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Ways to induce tolerance
CD80/86 (B7.1/
B7.2)
CD28
TransgenicIDO, TGFb, IL10, CTLA4, PD-1
Selective OGN
Immature DCs
VDR/1.25-(OH)(2)D3
FoxP3 Tregs
TRP depletion
HAA, Ky, 3-OH-Ky
costim. blockade
Janeway CA et al - Immunobiology, 5th edition
-
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Ways to induce tolerance
CD80/86 (B7.1/
B7.2)
CD28
TransgenicIDO, TGFb, IL10, CTLA4, PD-1
Selective OGN
Immature DCs
VDR/1.25-(OH)(2)D3
FoxP3 Tregs
TRP depletion
HAA, Ky, 3-OH-Ky
costim. blockade
T cell anergy
Janeway CA et al - Immunobiology, 5th edition
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The future............
In-vitro organ manufacturing
Xenotransplantation - GT-knockout pig
http://www.youtube.com/watch?v=ibtXFG2c42A
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