Transplantation of tissues and organs

Historical surgery sedatives

Opium, ether, nitrous oxides, ketamin (1950s), then fluranes (1960s).

Problem with transplants

Immune system or immune response

1905

First successful cornea transplant

1908

First attempted knee transplant

1909

First pig to human kidney transplant

1936

First human to human kidney transplant

Sir Medawar (1944)

Showed that skin allografts between mice do not work.

1954

Kidney transplant between twins (who both lived for an additional 8 years)

1963

Lung transplant

1967

First heart transplant. First successful liver transplant (patient lived for a few more months as cancer spread to new liver.)

1968

Bone marrow transplant between siblings.

1973

Bone marrow transplant between non-related people.

1981

First combo heart and lung transplant

Autologous

Self transplant (from patient back to patient)

Syngenic

Transplants between identical twins

Allogenic

Transplant between same species

Xenogenic

Transplant between species (ex. pig to human)

Organ evaluation (deceased donor)

did the donor have any: blood/liquid-born diseases, cardiovascular issues, exposure to viruses or other pathogens, or organ damage? Also consider size of organ.

Organ evaluation (Live donor)

Tolerance of removal: will they survive surgery and can body compensate? Cardiovascular health, cancer screening, and pathology.

HLA (Human leukocyte antigen) Typing

Proteins on the cell surface to tell the immune system not to attack it. Expression pattern is codominance. Class I-A, Class I-B, and Class-DR is linked to successful kidney transplants.

Hyperacute rejection

Antibody-driven, which activates the complement cascade where floating proteins bind to it and cause thrombosis. HLA or ABO rejection, occurs within 24 hours of transplant.

Acute/ delayed onset rejection

No initial response, but macrophages identify it as foreign and the adaptive immune system (T cells mount response and kill the organ). Occurs within 10 to 30 days.

Chronic inflammation/ foreign body response

Joint or artificial implants. Happens over months or years. T cells never accept organs (and symptoms similar to autoimmune disease). Local fibroblasts activate, generating fibrotic tissue around, typically calcifying the transplant.

Graft vs Host Disease (GVHD)

Occurs mainly in bone marrow transplant. T cells of donor attacks the cells of host.

Immunosuppressants

For all allograft recipients. Azathioprine - blocks DNA synthesis (taken before surgery).

Corticosteroids - Decreases transcription. Blocks immune system, but anti-inflammatory. Side effects on other tissues.

Cyclosporine and Tacrolimus - Specifically inhibit T cell activation (long term)

Donor incompatible transplants

Recipient has chemo or radiation to deplete their immune system and kill bone marrow. Get organ and myeloid stem cell transplant from donor.

Alpha Gal

Gene silenced in old-world primates, but expressed in other animals. Triggers immune system as hardcore foreign (leading to hyperacute rejection).

Alpha Gal Knockout Pigs

Four genes specifically knocked out to avoid hyperacute rejection.