Arthur M. Silverstein

Developmental Aspects of Immunity

Publisher Summary The chapter focuses on the developmental aspects of immunity. The ontogenetic development of immune responses in the immature animal and the developmental cellular stages of the immune response in the adult animal are discussed in this chapter. The cellular mechanisms underlying the several immune responses have not received the full attention either to the evolutionary principles underlying the development of all biological systems or to the broad biological rules that govern the proliferative and differentiate activities of cells in any biologically functioning system. The chapter reviews the immunological status of fetal and neonatal mammals as well as several aspects of the ontogeny of the immune response when examined by the most sensitive technique presently available. Developmental stages of immune reactions and their mutual relationships such as relationship of phagocytosis to specific cellular reactions, relationship of delayed hypersensitivity to antibody formation, and dynamics of antibody formation are also presented in this chapter. The increase of immunological capacity with age and the appearance of natural antibodies result solely from specific antigenic stimulation; the chapter discusses the Unitarian concept of cell differentiation and proliferation underlying any form of immunological response. Several methods for studying developmental aspects of immunity and immunological development are also discussed in this chapter.

Immunologic Maturation in utero: Kinetics of the Primary Antibody Response in the Fetal Lamb

The kinetics of the primary antibody response to bacteriophage φX174 have been studied in the fetal lamnb in utero after permanent indwelling catheterization of the fetal blood vessels. The initial antibody response by the developing fetus to this form of antigenic stimulus is comparable to that found in adult animals and shows none of the characteristics of the immature immunologic response that have generally been ascribed to fetal and neonatal animals.

Autoimmunity versus horror autotoxicus: The struggle for recognition

Historical insight: Paul Ehrlichs dictum of horror autotoxicus and the changing orientation of the field inhibited acceptance of the reality of autoimmune disease.

On the mystique of the immunological self

Since the time of Paul Ehrlich 100 years ago, we have known that the immunological apparatus somehow inhibits most damaging autoimmune responses while permitting a response to exogenous immunogens. With the discovery of tolerance, the concept of immunological surveillance, and especially with the discovery of HLA restriction of T‐cell recognition, the term “the immunological self” and the phrase “self‐nonself discrimination” have gained wide currency. Immunology has been called The Science of Self, and self‐nonself discrimination has been assigned as the driving force for its complex evolution. The concept of self has thus been given such mystical trappings since the time of Macfarlane Burnet that recent workers have felt free to pronounce it the central paradigm of modern immunology, and to claim to overthrow it! In this article, we challenge some of the more egregious claims about the immunological self by recalling important historical findings, by reviewing the mechanisms of Darwinian evolution, and by remembering that the general pathology of immunogenic inflammation shows that the immune response cannot discriminate between the benign and the noxious.

Clemens Freiherr von Pirquet: Explaining immune complex disease in 1906

What only one person accomplish in a lifetime? Pirquet, an exceedingly curious pediatrician with acute powers of observation and deduction, not only solved the riddle of serum sickness and developed the concept of allergy, but also made contributions to the study of nutrition and aging.

Darwinism and immunology: from Metchnikoff to Burnet.

Historical Insight: During those periods when immunology was oriented toward medical or biological subjects, Darwinian concepts predominated. These included Metchnikoffs phagocytic theory and Ehrlichs receptor theory during the early years and Burnets clonal selection theory after the 1950s. During the immunochemically oriented interim, instruction theories were not so much anti- as a-Darwinian.

The Clonal Selection Theory: what it really is and why modern challenges are misplaced

Historical insight: The clonal selection theory of antibody formation has recently been subjected to challenge from many quarters. A review of its history and that of scientific theories in general points to the importance of distinguishing between the central hypotheses of a theory and its subsidiary implications.

Cellular versus humoral immunology: a century-long dispute

Historical insight: Immunologys founding fathers argued fiercely about whether Metchnikoffs phagocytes or Ehrlichs antibodies were the most important mediators of immunity. Antibodies won out, but even after lymphocytes re-established cellular immunology, the humoralist-cellularist divide persisted.

The lymphocyte in immunology: from James B. Murphy to James L. Gowans.

Historical insight: Between 1912 and 1921, James Murphy established conclusively the role of the lymphocyte in tissue and tumor graft rejection and in protection against infection. Contemporary mainstream immunology paid little attention to these findings, until the lymphocyte was “rediscovered” with the advent of modern cellular immunology after the mid-1950s.

Visna Virus Infection of American Lambs

Random-bred fetal and 4-week-old American lambs, inoculated intracerebrally with visna virus, developed a persistent infection in the brain and sometimes in the lung. The pathologic changes present in these lambs were similar to the early lesions of visna in Icelandic sheep, thus providing a possible model for the study of virus-induced demyelinating disease.