Kidney Transplantation: Past, Present, and Future

Primitive, Primary and Potent
The Complement System Kills Strangers, But Gets Little Respect
 Mention "immune system," and most people think of the antibodies, and of B- and T-lymphocytes which guard us against nasty strangers. (A loss of kind of T-lymphocyte, or T cells, causes the decline in immunity we call AIDS).

 But there's another part of the immune system that's just as deadly -- and much quicker on the draw. It's called "complement," and it's a key obstacle to plans to transplant organs between species. What is complement? It's an ancient defense mechanism that uses at least 30 proteins in the blood. It was named "complement" because the system helps antibody (defined) kill invaders.

 How does complement "recognize" strangers?It marks any cell which do not have certainprotective proteinson their outsides. The antibody system, in contrast, recognizes and locks on to specific foreign proteins on the outside of foreign cells, and, in many cases, activates complement.

What happens then?The complement's markers, with or without antibody, attracts certain white blood cells called phagocytes, and they destroy the invader. The difference between thehumoral-mediated immune systemand the cell-mediated system, says John Atkinson of the School of Medicine at Washington University in St. Louis, is "how the foreign cell is recognized, not in the final pathway of destruction."

 Tell me more about the proteins that protect a cell against deadly complement attack...The genes in practically every human cell which is in contact with the bloodstream make at least three protective proteins. These proteins appear on the cell membrane:

• One, called MCP , prevents complement molecules from attaching to the cell.

 Another, called DAF, destroys any complement which does manage to bind to the cell.

 If that sounds complicated, maybethis diagram will help.

 What does a complement attack look like?Complement causes hyperacute rejection (defined) which kills foreign bodies much faster than a cell-mediated immune attack. Within minutes of the arrival of an invader, complement gloms onto it, clogging the blood supply, and causing the invader to turn blue or black. In some cases, the complement calls in phagocytes (white blood cells which digest invaders). In other cases, complement does the killing by itself, by breaking the cell mebrane of the invader.Almost as Deadly as a Corny JokeIf the complement attack is so fast and furious, how can anybody consider transplanting organs from pigs? Wouldn't they be dead within minutes?Perhaps not -- if scientists can "fool" the complement system by genetically modifying pigs so their cells produce those protective proteins on their outsides. In fact, scientists have already done this with pigs, which will probably be used to supply transplant organs within the next year or so.

 Why doesn't the complement system attack the baboon cells that were transplanted to Jeff Getty?Because baboons are so similar, genetically, to humans, that their cells display similar protective proteins (defined).

 What happens when the complement system screws up?It can cause grave diseases like acute hemolytic anemia -- in which complement and antibodies attack the red blood cells. Or, if the body cannot get rid of accumulated complement and immune cells after the immune system wins a battle, the result can be rheumatoid arthritis, or a kidney disease called glomerulonephritis.

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