Our T and B cells, and our antibody molecules
Evolved four hundred fifty million years ago, as tools, (1)
Protecting from the microbes plaguing early vertebrates,
Perhaps in some Ostracoderm, or even tunicates.
Motility of creatures in the late Devonian: (2)
Tiktaalik, on its lobe fins, might have been the early one, (3)
To wriggle from the sea to shore, where brand new microbes dwelled.
Survival would require that these new pathogens be quelled.
(There are some types of fish that wriggle on the land today.
“Mudskippers” live in shallow waters and crawl out to play
On land, where males do mating dances, hoping to impress
A fertile female, who will lay her eggs; but I digress.)
As “bugs” mutated, the immune response had to adapt.
Without such adaptation, vertebrates might have been scrapped.
Both cellular and humoral immunity arose,
For quick responses to evolving microscopic foes.
A thymus grew for T cells and a bursa for the B;
Cooperation ‘twixt the two turned microbes to debris.
When complement was activated, pathogens were doomed. (4)
For that marked them as foreign, which our phagocytes consumed.
“Hooray!” you say. Hold your applause, for there were side effects.
Control of inflammation has turned out to be complex.
Although it’s advantageous when it’s fighting off disease,
When errant, it kills normal cells or leads to allergies.
Some processes escape control. Autoimmunity
Occurs when antibodies misdirect affinity
And stick to our “self” antigens; then tissues are destroyed
When phagocytes munch on the cells discretion would avoid.
An anti-bug response is good, but when it goes awry,
Immune complexes may get stuck in our glomeruli, (5)
Or small blood vessels anywhere and tissues get inflamed.
Our immunologists say errant Tregs should be blamed. (6)
An autoantibody may be made to anything:
To any tissue, molecule, (or venom of bee sting.)
To DNA or RNA or antibodies, too, (7)
No limits to the mischief the immune response can do.
So, once again, the good and bad both started hand in hand
Before old lobe-finned creatures wriggled from the sea to land.
For, as life was evolving, we now know mistakes were made.
The best that evolution earns is just a B+ grade.
(1) This is our best estimate, based on rates of mutation in similar immune associated molecules of different species and our constructed family trees.
(2) The Devonian Age: about 420-360 million years ago.
(3) Tiktaalik Roseae, a fossil of a tetrapod estimated to have lived about 375 million years ago. Tiktaalik fossils were first discovered near Nunavut, Canada in 2004 by Neil Shubin. The name, Tiktaalik, meaning, “large, freshwater fish,” comes from the local, Inuktitut language.
(4) Complement is a cascade of molecules activated by antigens to which antibodies have bound. Such complexes are recognized as signals inviting phagocytes to eat.
(5) Glomerulonephritis is a common complication of circulating immune complexes.
(6) Tregs, a type of CD4+ T cell normally suppress B cells that might make autoantibodies.
(7) Antibodies to nucleic acids produce Lupus Erythematosus and related diseases. Rheumatoid factor is an antibody against another antibody molecule. One antibody is the antigen, the other the antibody. These circulating complexes in both classes of disease can damage glomeruli.