immunological big bang

[mattbimbo]

i thought i'd go fishing for any ideas that people may have regarding the evolution of adaptive immunity.

 

for those who don't know what adaptive immunity is, it is the part of the immune system that is involved with pathogen processing and specific recognition. within our lifetime, our immune systems undergo evolution, of course its capacity to do so does ultimately influence our final evolution.

 

from a thread last week, i raised the point that the first appearance of molecules which are central to the adaptive immune response date back 400-450 million years ago/the Devonshire period in sharks/cartilaginous fish. in this same thread, another writer pointed out that acorn worms might precede the sharks.

 

why an adaptive immune system first appears in sharks is considered to be a result of increased predation and absorbance of pathogens. (can anyone tell me if internal reproduction begins with the sharks too? because this could be a driving force for the evolution of adaptive immunity too.)

 

why acorn worms may (still waiting for sequencing of its genome) have an adaptive immune system is because they evolved the first circulatory system which would disperse pathogens within an organism.

 

but a recent article published in PNAS suggests sea urchins may be first.

 

any ideas anyone?

[Halucigenia]

I have just been reading this: Evolvability

from Marc Kirschner and John Gerhart (of The Plausibility of Life fame)

 

I have been interested in their theories since reading The Plausibility of Life.

 

I don’t know if it's what you are after, but it goes a long way (for me) in explaining how the immune system has evolved.

 

Here's the relevant bit, but the whole thing is well worth a read.

 

The best known of the exploratory systems is vertebrate

adaptive immunity' date=' which can produce any one of 1 million

different antibodies with high affinity for any of an even larger

number of antigens, without the animal’s foreknowledge of the

universe of antigens. In this system, variation in T cell receptors

is achieved by random recombination and sloppy joining

among several genes. Each T cell expresses a single recombinant

T cell receptor that is activated by an antigen-presenting

cell with the appropriate antigen, and therefore, the cell is

stimulated to proliferate. Here, variation (by recombination)

comes first, followed by selection (reaction with the antigenic

peptide presented on another cell). Similar considerations

hold for the generation of diverse IgGs of B cells.[/quote']

 

It seems, to me, to be saying that adaptive immunity is exploratory in the sense of exploring the possible “antigen space” and when it hits on something that works it can then produce specific antibodies. Also that evolution has preserved this “sloppy” joining, that is to say imperfect replication, as it is a successful adaptive trait i.e. its good for organisms to do a bad job in replicating these genes thus facilitating variation in the immune system (facilitated variation being one of their “catch phrases”).

 

My guess is that not only is adaptive immunity an exploratory process, but it is also a conserved core process (another of their terms), so it should have been about for a very long time. Conserved Variability to coin a new term?

[mattbimbo]

i read the article. Although neither of the authors are dedicated immunologists they consider adaptive immunity to be a prime proof of their system biology hypotheses. But many of their ideas are in fact borrowed, from L Pauling who laid the initial ideas of antigen space to N Jerne who proposed the idiotype network; Both of whom won Nobel Prizes. In fact they reference themselves a little too much for my liking. But most of all to my disliking is that they don't include any reference to research which shows that the adaptive immune system is constantly sensing self - and creating tolerizing immune responses to itself.

 

Your attempt to discuss the genetic side of adaptive immunity was good but the reality is much more deep. The hyperrecombination of antibody and TCR genes is mediated by specific enzymes, the RAG recombinases which may exist in sea urchins but certainly existed in sharks 400-450 million years ago, which recognise specific targets; Nothing 'sloppy' at all. It has to be a highly controlled process, a non-specific recombinase would destroy genetic integrity.

 

I'd recommend having a read of the mechanisms of hyperrecombination, they are very impressive.

 

I like the term 'conserved variability' , it might be one for the future.

 

And thanks for replying, but I am most interested in what ideas people have for the evolutionary events which led to AI.

 

For instance, the reason I'd like to know of cartiliginous fish had their offspring via intrauterine mechanisms, might explain the need for tolerance as a factor in promoting the development of AI. Think of it, sperm as a potential pathogen.