Jonathan W. Uhr

Regulatory Effect of Antibody on the Immune Response

Publisher Summary This chapter deals with the regulatory effect of antibody on antibody formation. It is possible to analyze those factors that influence the process of antibody synthesis. Certainly antibody, the end product of the process, is among the most potent and specific of inhibitors of antibody synthesis. That this inhibition results from the interaction of antibody with antigen neutralizing the immunogenicity of the latter seems likely, and the evidence for this is critically presented. The potential use of this mechanism is suggested by its effectiveness in the enhancement of tissue grafts, its use in the therapeutic prevention of anti-D antibody responses in mothers of Rh-incompatible fetuses, and its possible role in the induction of some types of immunological tolerance. The immune response represents a predictable series of events, characterized by the sequential appearance of several classes of γ-globulin antibody molecules and the expression of various cell-mediated immune reactions. One mechanism is described for regulating the concentration of immunoglobulin (IgG) in the circulation. The mechanism operates by increasing the catabolic rate of IgG when the serum concentration is abnormally increased as, for example, in multiple myeloma. Two mechanisms are described both of which regulate the immune response. These are alteration of antigenic stimulation and suppression of the immune response by passive transfer of specific antibodies prior to or shortly after administration of antigen.

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.

IN VITRO SENSITIZATION OF PHAGOCYTES AND LYMPHOCYTES BY ANTIGEN‐ANTIBODY COMPLEXES*

There are two recognized mechanisms by which lymphoid cells can acquire antibody activity on their surface. First, antibody-forming cells themselves may show such surface activity, as has been shown by Makela and Nossal.’ Secondly, Boyden and Sorkin2 have described the capacity of certain antiserums to sensitize macrophages passively. They have interpreted this phenomenon as being due to cytophilic antibody and have indicated that formation of such antibody is favored by the use of complete Freund’s adjuvant in the immunizing injection. In the studies to be reported, we extend earlier observations3 which indicate that there are two additional methods of passive sensitization: (1) Antigen-antibody-C‘ complexes can bind to the surface of small lymphocytes and passively sensitize such cells; and (2) Antigen-antibody complexes without C’ can passively sensitize macrophages and polymorphonuclear leucocytes (polymorphs). By passive sensitization of cells, we mean that such cells can bind “free” antigen further. Materials and Methods

A Model for the Regulation of Antibody Synthesis by Serum Antibody

Publisher Summary This chapter discusses a model for the regulation of antibody synthesis by serum antibody. The immune response (ImR) after removal of specific antibody was studied. In these experiments, antibody was removed specifically in two ways: (1) by successive exposure of aliquots of plasma of immunized animals to solid phase immunoadsorbents followed by return of the adsorbed plasma to them; (2) by exchange transfusion of animals immunized to two antigens with blood containing antibody of one specificity only, thereby depleting the other antibody specifically. Following the removal, there was a marked rise in serum levels of specific antibody, which frequently reached peak titers exceeding those prior to removal. The assay used in these studies was phage neutralization which is affected by the binding affinity of antibody. These experiments were repeated using an antibody assay that would allow estimation in molar terms. The results obtained support a model in which the level of serum antibody regulates the ImR by means of equilibrium with antibody in an immunogen-containing compartment.

Antibody Response to Bacteriophage ΦX 174 in Non-Mammalian Vertebrates.

Discussion and Summary After a single injection of 108–10 bacteriophage ΦX 174, the chicken, frog and goldfish were shown to produce approximately the same levels of neutralizing, rapidly sedimenting, γ-globulin antibodies as those previously obtained in analogously immunized mammals(5,6). Repeated injections of bacteriophage in the frog and goldfish, at intervals of 2–4 weeks, did not elicit an anamnestic antibody response. However, higher levels of antibody, mainly in the slowly sedimenting γ-globulin fraction were produced after immunization with bacteriophage in complete Freunds adjuvant, and, in the case of the goldfish, after further elevation of the environmental temperature to 32°C. Thus, in 3 classes of non-mammalian vertebrates a change was observed in the sedimentation properties of antibody γ-globulins produced during immunization. This change appeared similar to the replacement of 19S by 7S antibodies in the circulation of immunized mammals. These findings suggest that the mechanisms responsible for this phenomenon were present in the most recent common ancestors of terrestrial vertebrates and bony fish and that formation of rapidly sedimenting antibody is an integral and important part of the immune mechanism.

The use of glucose oxidase as a generator of H2O2 in the enzymatic radioiodination of components of cell surfaces

Glucose oxidase generates H2O2 via the conversion of glucose to gluconolactone in the presence of molecular oxygen. Coupling of this reaction to the lactoperoxidase-catalyzed substitution of iodine for hydrogen on the phenolic side chains of proteins present on the surfaces of murine myeloma cells leads to a very marked increase in incorporation of radioactivity as well as a significant improvement of cell survival.

Isolation and characterization of H-2 and TL alloantigens from the surface of mouse lymphocytes☆

Abstract H-2 and TL alloantigens were isolated from the surface of mouse spleen and thymus cells, respectively, by surface radioiodination followed by specific precipitation of a cell lysate. A major radioactive peak was obtained on acrylamide gel electrophoresis using anti H-2 and anti TL sera prepared in congenic strains of mice.

ACTINOMYCIN D: ITS EFFECT ON ANTIBODY FORMATION IN VITRO.

The formation of antibodies to bacteriophage T2 in vitro was inhibited by 5 X 10-8M actinomycin D. This result is consistent with the concept that antibody formation depends upon DNA-dependent RNA synthesis.

Functional Ribosomal Unit of Gamma-Globulin Synthesis

Nascent protein synthesis is associated with polyribosomes in extracts of lymph node cells removed from hyperimmunized rabbits, if the ribonuclease activity in such extracts is inhibited. Prior treatment of the cells with actinomycin D markedly decreases protein synthesis by polyribosomes.

Acute Hypervitaminosis A in Guinea Pigs. I. Effects on Acid Hydrolases.

Summary Acute hypervitaminosis A was induced in guinea pigs by oral administration of Vit. A. This treatment caused much of the activity of acid phosphatase, beta-glucuronidase and cathepsin to become unsedimentable at 15,000 g in homogenates prepared in 0.25M sucrose. Lysosome-rich fractions of hypervitaminotic livers released beta-glucuronidase and cathepsin more readily into the incubation medium in vitro than did control fractions. These events were accompanied by increases of serum beta-glucuronidase, and are compatible with a direct effect of excess Vit. A on lysosomes.