Basically, the evolutionary process explains how our innate and adaptive immune system protects us against all foreign, non-self-antigens, never before encountered by our bodies. This amazing feature of our genetic code derived from evolutionary biology is called the “antibody-encoding gene.”
The immune system is also pivotal to human survival, and thus, evolution. Critical physiological and developmental systems require resources, and natural selection should favor the optimal allocation of resources across these systems. The life-history theory is the branch of evolutionary thought concerned with variation in these allocation strategies. It uses the “allocation rule” to invest a portion of its energy to any single function and then stores excess energy resources for future use (Partridge, 1988). Such a role requires the evolution of a natural selection process to optimize biological resources. This anthropologic concept includes ontogenetic immunity over both a lifespan and across generations (McDade, 2005).
It is now believed that women have an evolutionarily tendency toward enhanced B-cell activation and thus, production of higher levels of antibodies and serum immunoglobin resulting in increased incidence of antibody driven autoimmune diseases. It is further proffered that this increased B-cell activation and antibody production in women is not an accident but rather an evolutionary advance to protect offspring from infectious diseases. It has also been reported that men may have fewer circulating T cells than women, further supporting a T cell-driven mechanism for the autoimmune sex bias (Kverneland, et al. 2016). A recent study showed that women have not only more antibodies in general, but also autoantibodies. This finding is significant, as autoantibodies are responsible for many autoimmune diseases. Evolution seems to preserve any mechanism to reduce the chance of infections, regardless of the cost. Although autoimmune disease may harm the mother, the reduced infection risk likely enhances their offspring's survival in classic Darwinian fashion.
Immunological (anamnestic) memory is another important evolutionary trait that improves host survival upon reinfection. Memory is a characteristic recognized within both the innate and adaptive arms of the immune system. Innate immune responses are traditionally thought to be non-specific and without the capacity to adapt, whereas adaptive immune responses recognize with great precision different pathogens (antibody-encoding genes) using gene recombination processes in the immunoglobulin gene family, and subsequently build immunological memory. Innate immunity has been termed “primed or trained immunity” and represents a de facto T-cell innate immune memory (Burnet, 1959). Adaptive immune memory is a relatively new evolutionary trait based in the immunoglobulin family and cells such as B and T-lymphocytes. It remembers previous pathogen encounters and can either repel a second invasion or quickly eliminate the recurrent invader by mobilizing a faster and more efficient immune response. Such an increased level of B-cells and resultant B-memory cells with persisting B-cell activation may also contribute to increased adaptive immune memory in females (Mihai, et al. 2019).
Specific adaptive immunity, depends upon the somatic diversification of antigen-receptor genes to generate a vast repertoire of cells, each of which express different antigen receptors. These lymphocytes, the specialized cell type of the adaptive immune system, use their cell-surface receptors to recognize antigenic configurations of specific pathogens and then respond to the antigen triggering by clonal amplification, cellular differentiation, and production of antibodies with the same antigen binding specificity. At birth, females have greater levels of B-cell activating factor (BAFF) while boys having greater proportions of immature/naïve CD5+ B cells from birth to 36 months (Lundell, et al. 2015). This contributes to a greater humoral immunity in females than males. It also suggests that sex differences in the humoral immune response may be present at birth with boys having a more immature/naïve immune system in general. The number of these developmental immunologic changes are conserved over time (Darwinian) producing greater basal immunoglobulin levels and higher B cell numbers in females potentially resulting in less infectious disease. Such examples of natural selection in the evolutionary development of the human immune system are numerous.
Discussion Questions:
If the evolution of innate immune cells, cytokines, antigen-presenting receptors preceded the evolution of the adaptive immune system, phylogenetically that should we consider the stronger immune component
Since the sex and gender biases presented in this discussion are evolutionary in nature, should they be considered the primal factors in sexual dimorphism? (Yet again, a loaded question without the additional discussion scheduled for Blog #19, but one worth considering now and again at Blog #19)?
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