Evolution of Adaptive Immunity II–Building on Innate Immunity
This is another installment in my response to chapter 6 of Darwin’s Black Box.
The first mouse Toll gene isolated turned out to be defective in two mouse strains that cannot respond to bacterial lipopolysaccharide (LPS), one of the pathogen-associated molecular patterns, or PAMPs, recognized by innate immune system pattern recognition receptors. These mice lack TLR-4 [Toll-like receptor-4] function; in one strain the defect is due to a point mutation in the so-called TIR domain (Toll/IL-1 receptor domain, since it is found in both Toll and IL-1 receptors), while in the other strain it is due to a null mutation that abolishes expression of the gene altogether. These mice are exceptionally susceptible to infection with gram-negative bacteria, which carry LPS on their surface, and cannot mount an adaptive immune response against them. This was, in a sense, the first proof that the loss of innate immunity had a discernible effect on the adaptive immune response, and served as a proof in principle that the adaptive immune response depended on an effective innate immune response, at least in some cases. The question remaining is: How general is this basic principle? Evolution of the innate immune system
And the answer is, the dependency of the “adaptive immune system” upon the “innate immune system” is very general. Just as the eukaryotic flagellum/cilium depends upon previously-existing transport structures which are shared by both the flagellum and cytoplasmic transfer machines, the adaptive immune system is, and apparently was from the beginning, part of and dependent upon the earlier-evolved innate immune system. Of course the “innate immune system” has also evolved in vertebrates, yet it continues to function much as it did in the past, while also priming and signaling the adaptive system to begin defending the body days after the initial response by the innate system.
As typical, my point is not to belabor the details, it is to give a sense of how the “irreducibly complex” adaptive immune system arose from and depends upon the innate system, while details are made available through links. The evolution of molecules is not the focus now, rather it is the fact that adaptive immunity reveals the characteristic and predicted evolutionary expectations of having been built into, and from the parts of, previously existing systems and structures. Some of the specific links to the past will come later, as some parts of adaptive immunity do not seem to have much (if any) role in innate immunity at the present time.
In my last post in this category, I pointed out that Toll and “Toll-like receptors” (TLRs) have evolved in the patterns expected of microevolution, or any other kind. The fact that other molecules of the immune system (adaptive and innate) reveal essentially the same patterns was also pointed out. But the fact is that Toll and the other “innate immune system” proteins are not simply to be found in the “innate” systems of vertebrates as well as in, for instance, fruit flies, they continue to utilize basically the same pathways–and they regulate and inform the adaptive response. All except the last part is borne out in the following quote:
In fruit flies, there is a very strict order of Toll pathway gene products starting with Toll and going on to dMyD88, Pelle, Cactus, and Dif/Relish, all of which are cytoplasmic proteins involved in the transmission of the signal from Toll, a cell-surface receptor, to the nucleus to induce the activation of specific sets of genes. The same order is found in the homologues of the Toll pathway found in the innate immune system in vertebrates(Fig. 1). The plant genes do not seem to be arranged in the same order. However, if one examines the plant genome carefully, there are signs of all these signaling elements. Evolution of the innate immune system
I included both the link to the figure, which shows the striking similarities between fruit fly and human immune systems (not including adaptive immunity, of course, which the fly lacks) and the part about similar parts but different order in plants, because the accidents of heredity have left an indelible mark on even the plants. Significant differences between animal and plant pathways do not seem surprising at all, because we split from plants very early.
However, so far in this post I have written little about adaptive immunity. The figure linked just above shows how close some of the innate signaling is in humans and in fruit flies, this link (picture and caption) shows how the human innate signaling pathway interfaces with adaptive immunity. Notice the TLRs (1-11), which are homologs with fruit fly Toll receptors, and MyD88 which also appeared in the previously linked figure in both humans and in fruit flies. As one may see from the illustration, the TLRs of the innate system signal infection (often via interleukins, ILs, or MyD88) in order to produce T helper cells (Th’s) in the adaptive immune system. The article from which this illustration comes goes into great detail about how the adaptive immune system relies upon the “irreducibly complex” (as Behe would have it) pathways of the innate immune system–which are little changed between humans and flies (which, one should recall, diverged before the “Cambrian explosion” that fills IDist chatter).
This puts the Toll-like receptors into perspective, as evolved molecules which retain something close to (but not identical with) the functions that Toll receptors perform in insects, and even in plants. These proteins are crucial to the function of our adaptive immune system, which surely is not to be ascribed to anything other than accidents of heredity, mutation, and environment (especially to heredity). No design function is served by the evolution of such a conservative complexity–and of course other aspects of our adaptive immune system are not at all conservative, when compared to the divergent and independent evolution of agnathan (lampreys and hagfish) adaptive immunity. And even if we may have shared the agnathan adaptive immunity, or vice-versa, clearly an independent evolution occurred in one line or the other one.
In keeping with my desire not to bog down in details covered well by others (see here for a reasonably good discussion of the immune system, and the basics of its evolvability), I will allow the linked illustrations to carry the argument that adaptive immunity evolved just as evolutionary theory predicts, by co-opting existing pathways and (in Behe’s phrase) “physical precursors.” Yet before closing I would like to note another generally neglected aspect of the “irreducibly complex” adaptive immune system, which is that it did not simply become complex at once and then not evolve (as Behe implies), rather adaptive immunity has evolved greater complexity while conserving its core structure (another commonality of evolution):
While increasing complexity of the adaptive immune system is evident with vertebrate evolution, the same basic construction of the adaptive immune system is conserved throughout the gnathostome [jawed vertebrate] radiations. The Evolution of Adaptive Immune Systems
So it is not as if the adaptive immune system was created in peak complexity, which did not evolve, instead it evolved its basic structure early, and then it evolved further. This should not be the case if such complexity could not evolve in the first place, for how would the irreducibly complex system evolve even more non-trivial complexity? A degenerate complexity might evolve under an ID scenario, but not the adaptive complexity that has evolved in adaptive immunity.
Of course one may tweak one’s “design theory” endlessly to have the unconstrained “designer” do whatever has happened, including the manipulation of mutations and natural selection. The trouble is that one needs constraints and entailed “predictions” if one is to do science at all, and evolution is what is constrained to produce the patterns we see (roughly the same in either microevolution and in macroevolution, at least in the aspects discussed here), while all known design constraints, like rationality and purpose, have the advantage of surpassing the limitations of evolution. The effects of such a transcending intelligence is not seen in life, except where humans have genetically modified organisms.
For instance, there is nothing at all in design that suggests that adaptive immunity should use the same pathways as innate immunity does in both humans and in fruit flies, and the same “physical precursors,” while evolution requires both (or at least modifications of the mentioned pathways–given the developmental constraints imposed prior to our divergence from the ancestors of fruit flies, that is). Evolution predicts the bridges that we see between the prior innate immunity and the later adaptive immunity, while one of the values of using intelligence to design a system is precisely so that one bypasses such constraints.
It is absurd to claim that design was necessary to make all of the rather small (very small by design standards) steps predicted by evolution, when in fact leaps are to be expected of intelligence. Future posts will discuss more of the evidence of small steps, which in fact produced two complex adaptive immune systems, simply because in vertebrate evolution no complex biochemical system can be transferred to a divergent line, while another complex evolution of a needed biochemical system is possible. A quote from one of the above sources well summarizes the matter:
This consistency of function, structure, order, and purpose over such a wide evolutionary range is a most impressive example of the evolution of a biological function, save for essential processes such as DNA and RNA replication and cell division. Evolution of the innate immune system
This is part of a series of posts that I am combining into one long post, which may be found at Darwin’s Black Box.