 The adaptive immune response, at least the version practiced by humans, appears to be a novel development that is restricted to vertebrates. Innate immunity, on the other hand, is found in all organisms, but only vertebrates seem to have developed a sophisticated mechanism that is able to recognize nearly every molecule that enters their domain, an apparatus that remembers past events and can marshal an "improved" response upon encountering an invader for a second (and later) time. This state of the art form of immunity is widely distributed in the vertebrate kingdom, and even "primitive" fish, like sharks and rays, share this same system with their more "advanced" cousins. But is it true that only vertebrates have managed to develop an adaptive immune system? Perhaps not. A recent article suggests that fruit flies, my favorite organism, seem to make use of an adaptive response of sorts when faced with viral infection. Although the mechanism that they use for defense against this kind of attack is quite different than that of vertebrates, it does result in a kind of immunological memory that is characteristic of vertebrate immunity. There are other examples. For instance, there is some evidence that snails can synthesize a diverse group of proteins that that have antibacterial activity. Even bacteria and archaea, organisms that are considered near the bottom of the evolutionary tree, make use of CRISPR to mount a specific defense against invading viruses, incorporating viral DNA into their genomes so that their response can target a specific marauder. One other fascinating (to me) point is worth discussing before I get off the subject of the possible diversity of adaptive immunity. There is a tiny group of living vertebrates, one that includes hagfish and lampreys, that do adaptive immunity differently. These jawless fish (all other vertebrates have jaws and are placed in a separate superclass) don't employ immunoglobulins (see below for a definition of this term) in their immune system. Instead, they make use of an entirely different protein in the construction of the molecules they use for defense. What this indicates to me is that the adaptive response can be fashioned in quite different ways, and that it may very well be that the scientific community may have missed finding adaptive immune systems in groups other than vertebrates because they may be so different than the systems we know about. Of course that's only a guess from a relatively uninformed observer. OK. Let's dig in. Adaptive immunity can be divided into two parts. There's the humoral response and there's cellular immunity. I wondered about the first term. It doesn't mean that this branch of immunity is funny. The word "humoral" has roots that go back to the fourteenth century when physicians thought that one's state of health was dictated by bodily fluids, the humors. The word now means fluid-based. In the current context it indicates that the responsible parties for humoral immunity occur in the non-cellular portion of the blood. The main players in the humoral system are antibodies, a term that was coined in 1891 by the legendary physician/microbiologist/immunologist and Nobel Prize winner, Paul Ehrlich. Antibodies are proteins, immunoglobulins, that are specialized for sticking to entities called "antigens" - meaning any molecule that upon capture by an antibody can induce an immune response. A cartoon version of an antibody shown in the act of binding to an antigen is depicted at the right. Below it is a more detailed and realistic picture sans antigen. Notice that this particular antibody consists of four chains, two longer "heavy" chains, and two shorter "light" chains, all of which bind rather tightly together to make a functional molecule. I should say a bit about the bottom part of the illustration at the right. What you're looking is a three dimensional rendering of the surface of an antibody. It was produced using two resources. The first is a collection of all the "solved" protein (and nucleic acid) structures in the universe. Solved in this case means that the position in three dimensions of virtually all the atoms in the molecule have been worked out. These coordinates, essentially a series of numbers assigned to each atom, are stored in the PDB, the Protein Data Bank, a public facility managed by Rutgers University and the University of California, San Diego. I searched the PDB for an antibody and found the one pictured. In order to display the structure and to manipulate it, I made use of a second public resource, "UCSF Chimera", a computer program from the University of California in San Francisco. It takes the raw data from a PDB file and creates a three dimensional depiction that can be manipulated on a computer screen. There are several such programs, but I've gotten to know Chimera fairly well and I use it often despite the fact that it rather complicated. If you'd like to explore the structure of antibodies and other proteins using a simpler program, look up "molecular modeling software" in a search engine. Or simply go to the PDB site (the URL is above) and use the modeling program found there. Antibodies are unique. All other proteins bear a specific sequence of amino acids, the monomeric units from which proteins are constructed. The amino acid sequence of a protein is dictated by a corresponding gene. In any particular organism, for any specific protein, there may be minor differences in the gene that codes for the amino acid sequence, but in general these are limited to one or two substitutions. Antibodies by contrast, occur in millions of forms, each with a different amino acid sequence, each one with the capability of binding a different antigen, each one dictated by the sequence of a different gene. The complex story of how this vast assembly of proteins is generated is the subject of the next posting.
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