Kinetics of Antibody Formation and Regulatory Aspects of Immunity

This paper, which is to be read in conjunction with that of Dr. J. F. A. P. Miller earlier in this volume, addresses itself to the kinetics of antibody production and to the regulation of the immune response. It is divided into four main sections. The first examines the kinetics of antibody production to a single, strong challenge injection of antigen. The cellular events involved in the latent period and the subsequent exponential phase of antibody production are examined from the viewpoint of four key concepts: triggering, clonal expansion, IgM to IgG switch and affinity maturation. The second section examines the major regulatory influences and feedback loops in immunity. Antigen is discussed as an agent capable of causing tolerance as well as triggering. Antibody is considered an important regulator, and the mechanisms of IgM-positive feedback, IgG-negative feedback, and tolerance and blockade effects of immune complexes are outlined. Immunological memory, the opposite phenomenon to tolerance, is briefly described, as is the importance of genetic factors. The third sections looks at more complex models of the immune response, and in particular at the lessons to be learnt from tumour progression. The importance of three different kinds of cell-mediated killing is discussed, as is the combinatorial influence of B and T cell activation. Attention is drawn to the reasons for believing that tumour progression eventually will lead to immunological non-reactivity, and to the fact that there are analogies between growth of tumours, starting from a single cell, and growth of foetuses. The fourth section finally poses the question of the immunological privilege of the developing foetus. While there are more questions than answers in this field, anatomical barriers and antigen as a blocking factor probably both play important roles.