I would like to share with you some knowledge that very few people in the world have. The topic is a very hearty one; Immunology, considered to be one of the most difficult in the health sciences. However, the immune system is of critical importance not only in defeating pathogens such as bacteria and viruses, but also in clearing the body of damaged tissue and eliminating cancerous growths. I will introduce some vocabulary for the simple reason that without it, this post would become very long, even for me. It is said that a picture is worth a thousand words, well, in Immunology, some words are worth about the same.
In a short series of posts, I will introduce an immune system process with the impressive title; Somatic Recombination, or, in this context, V(D)J Recombination. This process is significant for many reasons outside its critical and sole function; to build receptors. These receptors, also called antibodies, or Immunoglobulins, are capable of recognizing bits and pieces of invading pathogens and other substances that might harm the body. Of particular significance, the building process has potentially dangerous ends because it includes not only the cutting out and elimination of sections of an individual's DNA, but also the intentional introduction of mutations into the recombined DNA strands. Also, the process, when viewed across many Immune System cells, is an example of selection. It is not the same, of course, as natural selection occurring at a macroscopic level, but at the basic level, it does as it involves the survival and proliferation of those cells with receptors containing the sequence of amino acids that will best bind to a given antigen; the name given to the bits and pieces which stimulate our immune system into action.
Another interesting note about this process is that it is closely related to the process by which retroviruses insert their genetic information into the DNA of their host cells, i.e. human cells, which in turn can cause disease. In fact, the RAG (Recombination-Activating Gene) protein which directs the process is arranged differently from other human genes suggesting that it was evolutionarily adapted into our genome making Somatic Recombination possible.
I have often felt, during my studies that humans seem to be fabric into which is woven parts of many different molecules and organisms that probably coexisted in mutually beneficial societies, a social symbiosis. I am of the opinion that this symbiosis is the key to the successful evolution of life rather than the necessary but misinterpreted “survival of the fittest” notion to which evolution is so often tied.
The Immune System, so far in my study, looks to me like a living model through which the evolution of life on Earth can be seen. First, it was necessary for me to resist the compulsion to anthropomorphize. The Macrophage, a staple cell of the Immune System, was so named because it was seen as a “big eater”. I think this view is detrimental to a clear understanding and research path because we are essentially speaking of energetically favorable reactions not cells with a hankering for vittles. When I remove this lens, I see the symbiotic relationship with mitochondria as possibly allowing the re-tasking of complex energy seeking molecules to protective capacities and the establishment of self at the cellular level. I see that it's not a matter of destroying non-self, there is actually more non-self-inside us than self, it’s a matter of information dissemination, examination, and a resultant action. To illustrate, consider that molecules called MHC which present pathogen derived peptides to T cells and elicit an immuno-protective response. These MHC molecules will present peptides from the individual’s own healthy proteins in the same manor if an infection is not present. This presentation should, it would seem, result in no action by the T cells, but considering auto-immune disorders of unknown pathogenesis, perhaps this is not always the case. Pathogenesis is the origination and development of a disease.
This is just the very tip of a large and fascinating iceberg. I hope my explanation of Somatic Recombination in antibody production serves well in sparking interest in a study which has saved countless lives and may yet shed light on the evolution of life itself.