The effect of serum‐sensitiveness and precipitin formation upon the efficacy of diphtheria toxoid and toxinantitoxin mixtures in promoting antitoxin production

Abstract

EARLIER work on the subject of passive immunity has shown that antitoxin given to a sensitive animal is rapidly lost from the circulating blood. The rate of disappearance has been traced in rabbits previously sensitised by small doses of serum such as are present in 1.0 C.C. of toxin-antitoxin mixtures used for human immunisation (Glenny and Hopkins, 1922). It became evident that this rate of loss might have an important bearing upon the effect of an injection, in a sensitised animal, of a toxin-antitoxin mixture, causing possibly the rapid elimination of either the antitoxin alone or the mixture as a whole. It was also considered that, apart from the question of direct loss of material injected, the cellular activity and the precipitin formation which follow the injection of serum into a sensitive animal might inhibit or interfere with the immunising power both of toxoid and toxin-antitoxin mixtures as primary and secondary stimuli. I n this paper, we shall deal with experimental work directed to investigate these two aspects of the subject.The possibility of a rapid elimination of the antitoxin from a toxinantitoxin mixture when injected into a serum sensitive animal was investigated on guinea-pigs. These animals were given toxin-an titoxin mixtures in doses sufficiently large that if the antitoxin alone were lost, there would remain in the circulation several lethal doses of toxin ; guinea-pigs not previously sensitised were used as controls. The serum-sensitive animals did not succumb to the injection, and produced no larger swellings than did the control pigs. It was therefore concluded that if any elimination had taken place, both the toxin and an titoxin had been eliminated from the circulation. Table I. and charts 1 and 2 show the results of an experiment upon the influence of precipitin formation upon the antigenic effect of a toxin-antitoxin mixture (T.A.M.) given as a secondary stimulus.Previous experiments had shown that in a normal rabbit precipitin production begins about the seventh day and is thus less rapid than in a sensitive animal in which rapid production begins four days after the injection of serum, so that the injection of a toxin-antitoxin mixture, preceded four days by serum, would probably be unable to produce any immunity response if rapid elimination 805

Attempts to Induce Immunological Tolerance to Tetanus Toxoid and Xenogeneic Lymphoid Cells in Normal and Neonatally Thymectomized Mice

“…The 'crowding-out' phenom enon between several antigens has been previously described by Hopkins et al Diphtheria antitoxin responses were repressed in rabbits when normal horse serum was injected 4 days prior to immunization with diphtheria toxoid. They proposed that the observed phenomenon was due to a saturation of cellular activity by precipitin formation to horse serum (14). Nevertheless, it is reasonable to assume, in view of many previous negative experi ments with xenogeneic donor-host combinations, that the develop ment of a degree of tolerance by injection of newborn animals with lymphoid cells and antigen extracts of these cells would be demonstrable if antibody formation could be elicited to a specific antigen from donor cells.…”

The Effect of Antigenic Competition on Various Manifestations of Humoral Antibody Formation and Cellular Immunity

“…The initial description of the phenomenon was referred to as a "crowdingout" of the response by competition (2). Subsequently, the effect was considered to be mediated at an early inductive stage of the immune response but probably not at the level of the phagocytic cell (16).…”

Competition of Antigens as Influenced by Spacing of Heterologous Antigen Injections.

“…In some cases a crowding out has been shown to occur when an antigen is injected into an animal actively undergoing antibody formation against a previously injected antigen (6)(7)(8)(9). In some cases a crowding out has been shown to occur when an antigen is injected into an animal actively undergoing antibody formation against a previously injected antigen (6)(7)(8)(9).…”

“…In some cases a crowding out has been shown to occur when an antigen is injected into an animal actively undergoing antibody formation against a previously injected antigen (6)(7)(8)(9). Glenny et a L ( 8 ) found a crowding out of the response to diphtheria toxdd in guinea pigs when the toxoid was injected simultaneously with, or 2, 4, or 6 days after, an injection of normal horse serum. Glenny et a L ( 8 ) found a crowding out of the response to diphtheria toxdd in guinea pigs when the toxoid was injected simultaneously with, or 2, 4, or 6 days after, an injection of normal horse serum.…”