Lecture 11 Tpl Immunology

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



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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SKIN GRAFT


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ACCEPTANCE

SKIN GRAFT


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SKIN GRAFT

ACCEPTANCE

SKIN GRAFT


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SKIN GRAFT

ACCEPTANCE

REJECTION

SKIN GRAFT


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SKIN GRAFT

ACCEPTANCE

REJECTION

CELL PRECONDITIONING

SKIN GRAFT


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SKIN GRAFT

SKIN GRAFT

ACCEPTANCE

REJECTION


SKIN GRAFT


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SKIN GRAFT

SKIN GRAFT

ACCEPTANCE

REJECTION

ACCEPTANCE


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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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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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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MHC molecules are responsible for acute rejection after Tx


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Graft-infiltrating APCs


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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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n = 131985



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n = 131985



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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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CD80/86 (B7.1/

B7.2)

CD28

TransgenicIDO, TGFb, IL10, CTLA4, PD-1

Selective OGN

Immature DCs

VDR/1.25-(OH)(2)D3



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CD80/86 (B7.1/

B7.2)

CD28


Selective OGN

Immature DCs

VDR/1.25-(OH)(2)D3

FoxP3 Tregs

TRP depletion

HAA, Ky, 3-OH-Ky

costim. blockade



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CD80/86 (B7.1/

B7.2)

CD28


Selective OGN

Immature DCs

VDR/1.25-(OH)(2)D3

FoxP3 Tregs

TRP depletion

HAA, Ky, 3-OH-Ky

costim. blockade



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CD80/86 (B7.1/

B7.2)

CD28


Selective OGN

Immature DCs

VDR/1.25-(OH)(2)D3

FoxP3 Tregs

TRP depletion

HAA, Ky, 3-OH-Ky

costim. blockade

T cell anergy



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The future............

In-vitro organ manufacturing

Xenotransplantation - GT-knockout pig
http://www.youtube.com/watch?v=ibtXFG2c42A

Lecture 11 Tpl Immunology

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