The conservative physiology of the immune system

Abstract

Current immunological opinion disdains the necessity to define global interconnections between lymphocytes and regards natural autoantibodies and autoreactive T cells as intrinsically pathogenic. Immunological theories address the recognition of foreignness by independent clones of lymphocytes, not the relations among lymphocytes or between lymphocytes and the organism. However, although extremely variable in cellular/molecular composition, the immune system preserves as invariant a set of essential relations among its components and constantly enacts contacts with the organism of which it is a component. These invariant relations are reflected, for example, in the life-long stability of profiles of reactivity of immunoglobulins formed by normal organisms (natural antibodies). Oral contacts with dietary proteins and the intestinal microbiota also result in steady states that lack the progressive quality of secondary-type reactivity. Autoreactivity (natural autoantibody and autoreactive T cell formation) is also stable and lacks the progressive quality of clonal expansion. Specific immune responses, currently regarded as the fundament of the operation of the immune system, may actually result from transient interruptions in this stable connectivity among lymphocytes. More permanent deficits in interconnectivity result in oligoclonal expansions of T lymphocytes, as seen in Omenn s syndrome and in the experimental transplantation of a suboptimal diversity of syngeneic T cells to immunodeficient hosts, which also have pathogenic consequences. Contrary to theories that forbid autoreactivity as potentially pathogenic, the physiology of the immune system is conservative and autoreactive. Pathology derives from failures of these conservative mechanisms.

Long-term anergy in orally tolerized mice is linked to decreased B7.2 expression on B cells

“…Oral tolerance induction in naive status is a wellestablished phenomenon that depends on the type, timing and dose of Ag and the genetic background concerned (Faria and Weiner, 1999;Vaz et al, 2003).…”

From the diet to the nucleus: Vitamin A and TGF-β join efforts at the mucosal interface of the intestine

“…Such harmless non-self antigens are abundant in the intestine where numerous, often beneficial commensal bacteria colonize the colon and where digested food is continuously absorbed via the small intestine epithelium. An effective immune-regulation is a condition sine qua non for the gut physiology [12-15] and the importance of Treg cells to control and prevent aberrant immune responses directed towards self or non-self antigens and to establish tolerance has been demonstrated at length [16]. …”

Visita à imunologia

“…The mechanism proposed for "autoimmune diseases" was based on the emergence of self-reactive clones. However, these clones are present and activated in healthy organisms; they just do not show the progressive reactivity which is characteristic of the secondary immune responses -the so-called immune "memory" 14 . We are exposed to allergenic materials, however only some of us become allergic.…”

“…However, the interactions with antigenic materials are only able to trigger changes determined (specified, guided) by the structure of the immune system at that moment 14,28,29 .…”