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The evolution of complement and the alternative pathway
Published on June 29, 2017 34 min
Other Talks in the Series: The Complement System
Complement 3 glomerulopathy (C3G) and haemolytic uraemic syndrome (HUS)
- Prof. David Kavanagh
- National Renal Complement Therapeutics Service, UK
"The Evolution of Complement and the Alternative Pathway." I am Peter Lachmann, Emeritus Sheila Joan Smith Professor of Immunology in the University of Cambridge.
There are two ways to look at complement evolutionary history. The first is to look at the sequence in which complement was discovered, and that starts from the classical pathway, long before the alternative pathway. On the other hand, one can look at the evolutionary history, and that is different, starting from the alternative pathway, and the classical pathway being evolutionarily restricted to vertebrates.
That goes back to the late 19th century, when a number of workers, von Fodor, Nuttall, Buchner, observed bactericidal activity in normal serum. In 1894, Pfeiffer and Issaeff showed that you could lyse Vibrio Cholerae in the peritoneum of immune guinea pigs and also normal guinea pigs when they are given antibodies intraperitoneally. But the real discoverer of complement is Bordet in Belgium, who showed that when you add normal serum to a mixture of Vibrios and heated immune serum, this gives you lysis in vitro. He then went on to show, as well as Ehrlich and Morgenroth similarly had shown, that erythrocytes in the presence of antibody can be lysed by normal serum containing complement. He called it alexin - Ehrlich called it complement. The critical experiment was done in 1901, when Bordet and Gengou described complement fixation, thereby showing for the first time that complement is not just an activity, but was actually a substance.