Strictly speaking, the evolutionary development of the immune system should be the first topic of discussion, but I postponed it to after Blog #5 so as to initially provide a review of the molecular biology that is a significant part of the immune system’s evolution. I actually scattered evolution discussions throughout the book rather than a dedicated chapter and in retrospect, after doing some post-publication research on immune evolution and realizing its profound relevance, I could have kicked myself.
Next edition, I assure you it will warrant a full chapter, but in the meantime, the next two blogs will cover some of the most germane information on evolution and the immune system.
Around 600 million years ago (Neoproterozoic Era), multicellular organisms (metazoans) began to form followed by a remarkable diversification in such a relatively short time period (just a few million years) that it has been theorized as the “immunologic big bang” with the evolution of clonal selection, antigen receptors of lymphocytes, antigen-specific dominant immune tolerance (mediated by regulatory T cells), transcription factors, miRNAs and more, all following Darwinian selection. Innate mechanisms of self-defense were acquired during this evolutionary period producing generic surface receptors that recognize patterns on different classes of pathogens to trigger an inflammatory response to limit pathogen invasion. Vertebrates with jaws (gnathostomes) also developed an “adaptive” immune system that can recognize and initiate a protective response against potentially lethal pathogens. This evolutionary phylogeny occurred through Darwin’s process of “natural selection.” Another theory of immune system evolution was proposed in 1801 as Lamarckian’s “Theory of Inheritance of Acquired Characteristics” postulating that an organism can pass on physical characteristics to its offspring that the parent organism acquired through use or disuse during its lifetime. But this was refuted until the more recent development of a new generation of genome editing tools (e.g., CRISPR - lots more in Blog #32) that we are now experiencing. In these procedures the modified DNA inserts are passed on to other cells.
Most healthy humans have the capacity to turn on type 1 TH cells, interferons, inflammasome activation, and a multitude of other immune functions. But individuals differ in the degree at birth, during aging, sex differentiations, and when encountering new environmental factors. The origin of this diversity is rooted in our evolutionary pasts, with genes that control immune traits being among the most divergent in archaic genomes. The evolutionary roots of sex variants between males and females are directly related to the risks for immune-related diseases, including those linked to autoimmunity and viral infection.
Microbes (viruses, bacteria ,and archaea [prokaryotes], fungi, protists [eukaryotes]) existed in the cosmic environment prior to human evolution, 3 billion years (or so) ago. Thus, the human genome (host) was colonized by microbes creating the human microbiome (Blog #13). The ecosystem of coexistent environmental microbes along with the human microbiome (referred to as the “second genome”) having evolved through natural selection, is referred to as a holobiont (a discrete symbiotic ecological unit consisting of a host and other species living in or around it [Margulis, 1970]). Collectively, its genetic material is referred to as a hologenome. In that the phenotype of a holobiont is the result of the integrated activities of both the host and all of its microbiome inhabitants, evolution acts at the level of the holobiont to produce changes in the hologenome. More on this phenomenon in the embryology and pregnancy blog #8. But first, let’s continue with Part 2 of evolutionary development in Blog #7.
Discussion Questions:
Do you believe that the gene editing procedures (e.g., CRISPR) that can pass on the edits to other evolving cells is proof of concept for the Lamarckian theory of evolution?
Given that the hologenome is the genetic material of the holobiont, environmental microbes plus the microbiome, did it have an influence on immune system evolution, and if so, how and what effects?
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