UKC

Ive seen a couple of books on amazon that are £50-80+, im interested but not THAT interested in it!

Can anyone point me in the direction of some resources or books on the topic of how the immune system, WBCs etc came about in early organisms. Ive got a decent understanding of human physiology but dont know at what period of history it started to develop and how. Its not essential I know but its something thats intrigued me for a while.

In reply to Pesda potato:
This was the subject of my PhD!

The earliest extant organisms to have an adaptive immune system based on immunoglobulins (like ours) are elasmobranchs (sharks, skates and rays). Lamprey and hagfish are slightly older and also have an adaptive immune system but its architecture is very different, based around molecules called VLRs (variable lymphocyte receptors) which have a leucine-rich repeat motif. These seem to be functionally homologous to our immunoglobulin-based molecules but aren't well understood. It seems likely that the two systems arose independently of each other (convergent evolution) and the immunogloblin system flourished while the other didn't do so well.

Innate immunity is found much further back, with most organisms having some rudimentary form of innate immunity. A good example is sponges, which exhibit something that looks a lot like graft vs host disease if you force two unrelated sponges together. Plants also have quite sophisticated innate immunity.

Feel free to message me privately if you want to know anything else

In reply to kathrync:


Thank goodness - now I don't feel obliged to try to remember it all! Shark and camel antibodies are quite interesting, and useful.

In reply to Pesda potato:

UKC is an amazing place

In reply to Dave Garnett:


Yes, and another fascinating example of convergent evolution. I spent a while working on a project using shark antibodies to target drugs more accurately. They have advantages over mammalian antibodies for this purpose because they are smaller and the antigen binding site is single-domain so they are easier to engineer. Also the shark ones in particular have a long protrusion in the binding domain that can bind epitopes in pockets - the disadvantage is that the human immune system sees them as inherently foreign and tends to mount a response against them - humanising them tends to rob them of their special properties so I think it will be a while before we see these coming into clinical use (although there are already some therapies in use that use mammalian antibodies in this way).

In reply to kathrync:

... but we are using camelid single chain ABs in the lab (Lama, I think...), precisely because they are easily engineered and even expressed inside cells from a single transgene.

To Pesda potato:

Innate immunity is reasonably well conserved from flies to humans, so must have been present in our last common ancestor, some sort of worm that lived 550 My or so ago. In fact, the 2011 Nobel for medicine was given to a bunch of fly researchers because so many principles could be worked out by looking at a simple model organism.
There are differences, though, as one key class of immune receptors binds directly to structures e.g. in bacterial cell walls, while the fly versions use adapter molecules.

CB

In reply to cb294:


Oh, yeah - they are great in the lab - just not so good if you try to stick them into a mammal

In reply to kathrync:

With immunoglobulin-like domains occurring in so many other contexts apart from antibodies, it could be argued that it's V/J/D gene rearrangement and somatic hypermutation that make them special in the context of the immune system. If so, that would narrow Pesda potato's question down to the origins of those two diversification mechanisms.

Or perhaps it's helpful to think about the question at the level of cells - take one of those cell-lineage charts that immunologists like to stick on their freezer-doors, and cautiously apply the unfashionable notion of "ontology recapitulates phylogeny".

In reply to tev:

>... the unfashionable notion of "ontology recapitulates phylogeny".

That then leads to the even more deeply unfashionable notion that the reason they do so is that they are both, in some deeply logical (and un-Darwinian) sense, goal-orientated. And they are bound to behave/develop/evolve - at hugely different time scales - in rather similar ways. I.e the cells can't do otherwise. ... [[too late at night to get into such a vast subject!]]

In reply to tev:


Ig domains are useful stable domains providing a nice rigid structural module, why wouldn't they turn up in a variety of other receptors, especially in cells of the immune system where they are being actively expressed and recombined? In some situations where an adaptive immune response requires hypermutibility, that's what was selected for. Where they are stable building blocks as required in invariable receptor-ligand pairs, that's what you get. No mystery.


Eh?!

In reply to tev:

And as per my original answer, the phylogenetically oldest extant group in which V/D/J arrangement can be observed is elasmobranchs.

However, be wary with this because while some organisms use somatic hypermutation for this (which is what is usually taught at undergrad level), other organisms use other methods to achieve V/D/J rearrangement - for example many bird maintain pseudogenes and use a gene conversion mechanism instead. in other words, while V/D/J rearrangement is conserved from elasmobranchs, the mechanism for achieving it is not.

In reply to Pesda potato:

You can spend a lifetime looking at immunology, it is an immense subject. I don't know your background, but if you are interested to learn more generally then the BSI do a set of pages called bite-sized immunology http://bitesized.immunology.org which you might be handy.

Although immunology trained I can't really answer your question, but do remember that the platelets are important in immune defence in caterpillars! Many animals and fish have pathogen recognition receptors, like our Toll-like receptors which recognise bacterial or other 'harmful' material and may cause a direct response to push the adaptive immune system to respond in a given way.