Normergic and allergic inflammation

Abstract The first, ordinary or normergic response of the body to a foreign protein (pollen, vegetable protein, bacteria, foreign animal protein) that has penetrated the body tissues varies from a negligible reaction to a severe inflammation depending upon the inherent toxicity of the substance and upon the dose. The body is then more or less sensitized to the foreign substance, and upon repeated exposure to it the inflammatory response differs from the original reaction in that the onset is more rapid, the course more violent, and the resolution of the process slower. Hyperergic reactions of this sort analogous in many respects to conditioned reflexes occur not only in the clinical allergies but also in other forms of anaphylaxis, in idiosyncrasy, and in immunity. In contrast to the hyperergic state of allergy there is a hypoergic or anergic state in which the body fails to react to an excitant, a condition not to be confused with acquired immunity. As is well known, allergic reactions are influenced by the number and size of the sensitizing and shocking doses and by the time intervals. They vary from functional, vascular responses and hypertonus or spasm of smooth muscle to the severe necrotizing inflammation characterizing the Arthus phenomenon. Under certain circumstances specific granulomatous lesions result. Although it is possible that all the cells in the body may be sensitized, allergic reactions are ordinarily exhibited by the arterial system, connective and lymphoid tissues, and synovial, ectodermal and entodermal membranes, whereas the parenchymatous tissues are usually spared. Evidence is accumulating that many of the drug idiosyncrasies with reversible and irreversible tissue changes are in reality true hyperergic allergic reactions, the drug as such or the drug as modified by the body acting as a hapten. The hyperergic reactions in immunity are completed without injury to the body health. They represent a perfect adaptation of the body to the various antigens. A further complicating factor influencing certain inflammations is the reaction of specifically sensitized tissues to a nonspecific allergen. A typical example of this sort is the transitory positive tuberculin reaction in certain individuals following vaccination with cowpox virus. Moro and Keller consider such reactions to be parallergic. Other parallergic reactions are likewise involved in mixed infections, superinfections, and complications of infections. The severe hemorrhagic lesions experimentally produced in the Sanarelli and Shwartzman phenomena are likewise parallergic reactions, as are also the severe vascular lesions with thrombosis and gangrene produced by Marcus and Schmidt-Weyland in rabbits sensitized with certain bacteria or bacterial toxins and then injected repeatedly with adrenalin. It is possible likewise that the hemorrhagic necrotic lesions in the liver in eclampsia may result from the action of pituitary hormone in excess after sensitization of the individual by some foreign excitant. In analyzing the tissue changes of inflammation the role of the factors outlined by Rossle and appearing above in diagrammatic form must be considered.