ABSTRACT The immune system is usually seen as a collection of independent (specific) lymphocyte clones. Randomly generated and activated at random, these lymphocytes follow only their individual, clonal history. Thus, in traditional descriptions, immunological activity is neither systemic nor historical and is never âphysiologicalâ. However, recent descriptions show an abundant "auto"-reactivity in healthy organisms, an evidence of internal connectivity. The two major sources of immunogenic contacts, namely, dietary proteins and products of the autochthonous microbiota fail to induce progressive "secondary-type" clonal expansions (or "memory"). Natural IgM may arise in âantigen-freeâ organisms as they do in conventionally raised animals; actually, clonal receptors of both T and B lymphocytes are formed in antigen-free intracellular environments and are not driven by antigen exposure. Early in ontogenesis natural immunoglobulins are organized in characteristic patterns of reactivity which are robustly stable throughout healthy living; these patterns depend on genes known to be important in immunological activity. Predictable (not-random) variations on these patterns occur during infectious and autoimmune diseases, both in humans and experimental animals, which are correlated with different clinical states of these diseases. All this is incompatible with a random process driven by independent lymphocytes. In different pathological conditions, ranging from immunodeficiencies to parasite, allergic and autoimmune diseases, the organism develops oligoclonal expansions of T lymphocytes. In addition, oligoclonality is associated with high IgE titers and eosinophilia. We propose, therefore, that the physiology of the immune system is conservative and remains stable throughout healthy living. In several types of experimental and clinical diseases, this stability is broken by oligoclonal expansions of T cells. Specific immune responses, understood as the progressive expansion of oligoclonal lymphocytes, are expressions of immunopathology rather than immune physiology. A new explanation of the protective effects of anti-infectious vaccination is offered.