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Printable Handouts
Navigable Slide Index
- Introduction
- Two ways to look at complement evolution
- The historical evolution of complement
- Jules Bordet
- Complement components
- One hit theory of complement lysis
- Leon Rosenberg, 1965
- Molecular basis of complement action
- Identification of C3 as β1c globulin
- Hans Muller Eberhard
- Structure of C3
- Mechanisms of complement fixation
- The thioester reactions
- C3 coating bacterial flagella
- Archeo - complement system
- Structure of mosquito TEP1r vs. Human C3
- Primitive feedback
- Novel coping features of vertebrate complement
- C3b feedback and breakdown
- The properdin system
- 2nd coming of the alternative pathway
- The alternative pathway mechanism
- Absence of C3b breakdown
- The C3 tickover
- Initiation of alternative complement pathway
- How to inhibit C3b breakdown
- C3b bound to protective surfaces
- How to amplify feedback
- Nephritic factors
- Nef and disease
- Partial lipodystrophy
- Hyperinflammatory complement type
- C3bi+CR3 and inflammation
- iC3b
- Inflammation
- Neutrophils are essential for humoral inflammation
- Complement Receptor CR3
- Structure and domains of CR3
- iC3b reactions with CR3/CR4
- What does complement do?
- Thank you
Topics Covered
- History of discovery of the complement system
- Evolution of complement
- The alternative complement pathway
- Defects and diseases associated with complement
- Complement and inflammation
Links
Series:
Categories:
Therapeutic Areas:
Talk Citation
Lachmann, P. (2017, June 29). The evolution of complement and the alternative pathway [Video file]. In The Biomedical & Life Sciences Collection, Henry Stewart Talks. Retrieved September 1, 2024, from https://doi.org/10.69645/CKRF9447.Export Citation (RIS)
Publication History
Financial Disclosures
- Prof. Sir Peter Lachmann, Consultant: Gyroscope Therapeutics (no longer), Ionis
Other Talks in the Series: The Complement System
Transcript
Please wait while the transcript is being prepared...
0:00
"The Evolution of Complement and the Alternative Pathway."
I am Peter Lachmann, Emeritus Sheila Joan Smith
Professor of Immunology in the University of Cambridge.
0:12
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.
0:39
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.