Immaturity, Ageing and Oral Tolerance

Abstract

Vaz NM, Faria AMC, Verdolin BA, Carvalho CR. Immaturity, Ageing and Oral Tolerance. Scand J Immunol 1997;46:225-229 Founding studies of cellular immunology emphasized that tolerance to allografts could only be achieved early in the embryonic or neonatal period, suggesting that the establishment of self-tolerance, a main event in the organization of the immune system, would necessarily take place in immature hosts. Contradicting these ideas, oral tolerance is a common, daily phenomenon, easily achieved by a physiological route in adult immunocompetent animals. Furthermore, there is solid evidence that, after the neonatal period, the susceptibility to oral tolerance induction also wanes and that it may be restored by adoptive transfer of cells from young hosts. These findings are briefly reviewed here to emphasize that immunological activity is a continuous and ongoing epigenesis extending throughout the entire life of the organism, far beyond the early phases of ontogenesis. Nelson M. Vaz, Department of Biochemistry and Immunology, CP 486, Instituto de Ciências Biológicas, Universidade Federal de Minas Gevais 30161-970, Belo Horizonte, MG, Brazil THE DOMINANT IMMUNOLOGICAL PARADIGMWe refer to the 'dominant immunological paradigm' [1] as a large interlaced set of terms and notions based on the concept of specific immunological recognition of foreign epitopes (immunity) and its complement, the notion of self-tolerance (self/nonself discrimination). The current version of the paradigm is based in different versions of the Clonal Selection Theory of Antibody Formation [2]. An alternative paradigm should be able to define, discuss and explain immunological activities and immunological phenomena without relying on the distinction between foreign and familiar materials (self/non-self discrimination) or on the notion of self-tolerance (self-ignorance). Up to this moment, we are not aware of such an alternative being fully formulated.In a previous essay [3], we pointed to a confusion of domains of description inherent to the current paradigm, which confounds the structural dynamics of the immune system (its physiology) with immunological phenomena (such as specific immune responses) which take place in the domain of interactions of the organism acting as a whole 1 . In the present essay, we use the same way of seeing to describe the set of phenomena currently described as 'oral tolerance'. We will show that these phenomena are not explained by the current paradigm and require alternative systemic notions to explain them. SELF-TOLERANCE AND IMMATURITYCreated in the early 1960s, the current immunological paradigm was heavily influenced by experimental findings on bovine twins' natural allogeneic chimeras [4], the rejection of allografts in mice [5,6] and chickens [7,8] and the adoptive transfer of immunological competence by lymphocytes [9][10][11][12]. The Clonal Selection Theory hinged around the notions of self/non-self discrimination (self-tolerance) already emphasized in a previous book by Burnet & Fenner [13], exp...

Aging and immunoglobulin isotype patterns in oral tolerance

“…We believe, however, that the discussion on the effect of aging on oral tolerance invokes the very mechanisms responsible for its induction and maintenance (33).…”

“…increase in their susceptibility to systemic oral immunization following repeated (intermittent) oral exposures to antigens (12,15,32,33).…”

The conservative physiology of the immune system

“…When higher doses of antigen are used in the oral (or nasal) pretreatment, the animals respond feebly to subsequent parenteral immunizations and are said to be orally tolerant (24,25). However, with lower doses of antigen, animals that become partially tolerant may form significant titers of specific antibodies upon parenteral immunizations, although lower than in control animals without mucosal pretreatment.…”

Alteration of secretory IgA in human breast milk and stool samples after the intake of a probiotic — report of 2 cases

“…Identifiable experimental variables include: genetics; age, dose and timing of postnatal antigen feeding; antigenic structure and composition; epithelial barrier integrity, and the degree of concurrent local immune activation as reflected by micro-environmental cytokine profiles and the expression of co-stimulatory molecules on antigen presenting cells (APC) in the gut. The development of oral tolerance to food antigens and resident gut microbiota is of extreme importance for the development of the local and systemic immune response in infants [1][2][3].…”