Summary Solid organ transplant

Solid Organ Transplant

Transplant

 Exclusion – over 85 years, cancer, transmissible spongiform encephalopathy, TB
or HIV
 Grafts:
 Xenograft – between different species
 Autograft – from one part of the body to another
 Isograft – between genetically identical people
 Allograft – between members of the same species (rejection depends on
histocompatibility)

Immunology

 Histocompatibility antigens – major histocompatibility complex
 Human leukocyte antigen (HLA)
 MHC I – expressed on nucleated cells and present antigens to CD8 CTL
 MHC II – expressed on APCs to activate macrophages and B cells by presenting
extracellular antigens
 Adaptive and innate immune response

Drug Targets

 Signal 1:
 Interaction between TCR and MHC presented antigen
 Drugs – Anti-CD3 MAB
 Signal 2:
 Co-stimulation of receptor between T cell and APC (CD80/CD86/CD40)
 Pathways – calcium – calcineurin, mitogen activated protein (MAP) kinase or
protein kinase C (PKC) nuclear factor kappa B
 Signal 3:
 Growth signals activating the cell cycle
 Pathway – activation of PI-3K and mTOR

HLA Compatibility

 Minimise rejection by HLA compatibility and immunosuppression
 HLA-DR biggest determinant

Immunosuppression

 Induction – corticosteroids, Basiliximab, Alemtuzumab and ATG
 Maintenance – Ciclosporin, Tacrolimus, Azathioprine, Mycophenolate, Balatacept
and Sirolimus

Induction

 Basiliximab:
 Chimeric IL-2-R antagonist
 MOA – inhibits differentiation and proliferation of CD25 activate T cells
 Given 3-4 days after surgery
 Alemtuzumab: