The hard problems in immunology are not in the changes that have been identified and studied as specific immune responses and their regulation, but rather in global patterns (profiles) of activity which remain invariant amid ceaseless structural variation. The age of easy questions and answers may be over (Nicholson, 2014; Gilbert, Sapp and Tauber, 2012; Gilbert, Bosch & Ledon-Rettig, 2015).
As Anderson and Mackay (2014) tell us, Burnet moved autoimmunity from the fringes of immunology to the center of attentions. But, in Burnetian (clonal) immunology, the organism is only the place or dimension in which immune responses take place. Presently, however, the organism has returned to Biology as a fundamental explanatory concept and there is a renewed interest in the nature of life as a genuine scientific problem (Maturana, 2002: Nicholson, 2014).
After several decades of new findings in virtually every area of experimental biology, we may have reached conditions that allow a better understanding of autoimmune diseases, not as derived from the expansion of forbidden clones, but as disturbances of quite different origins in which lymphocytes come to play an important, central role. These disturbances may result from congenital abnormalities in organogenesis. For example, defects in Hox11 may change the pancreas, salivary and tear glands, the cochlea and the tongue and, secondarily, lead to type-1 diabetes (Lonyai et al., 2007); or, single gene inborn defects of the immune system itself that lead to complex autoimmune syndromes (Carneiro-Sampaio and Coutinho, 2006).
Allergic and autoimmune diseases may derive from functional mutations that change the permeability of the skin (Thyssen & Kezic, 2014) or in the permeability of the gut (Tripathi et al., 2009; Vanuytsel et al., 2013). As claimed by Parnes (2003) there is no essential distinction between allergic and autoimmune pathologies. Differences in the severity of infectious diseases may be related to the same processes involved in allergic and autoimmune diseases, such as oligoclonal T cell expansions (Vaz and Carvalho, 2015). Diseases may be seen as reductions in the flexibility of the organism that weakens its ability to face other forms of stress (Bateson, 1972). In this sense, ageing is the most common and inevitable change in the life cycle of metazoa and the collapse of immune activity is part of it.
Anderson, W., & Mackay, I. R. (2014). Fashioning the immunological self: the biological individuality of F. Macfarlane Burnet. J Hist Biol, 47(1), 147-175. DOI: 10.1007/s10739-013-9352-1
Bateson, G. (1972). The role of somatic change in evolution (pp. 346-363). New York: Ballantine.
Carneiro-Sampaio, M., & Coutinho, A. (2007). Tolerance and Autoimmunity: Lessons at the bed-side of Primary Immunodeficiencies. Advances in Immunology, 5I-81. DOI: dx.doi.org/10.1016/S0065-2776(07)95002-6
Nelson M. Vaz (2015). Self-tolerance revisited. Studies in History and Philosophy of Science, Available online. DOI: http://dx.doi.org/10.1016/j.shpsc.2015.11.006.
Nelson M. Vaz, Claudia R. Carvalho (2015). On the origin of immunopathology, Journal of Theoretical Biology, 375(1), 61-70. DOI: http://dx.doi.org/10.1016/j.jtbi.2014.06.006.
Post by Nelson Vaz, professor emérito do ICB/UFMG