Project Title: 14, Scope: Effects of Radiation on Living Organisms Radiosensitivity of Immune Responses and Mechanisms of Jmmune Reactions _ RX-03-O1-(b) (Cont'd.) responses, as compared with the same antigen (tetanus toxoid} administered either in soluble or adsorbed form, In order to provide a broad basis for the observed efficacy of primary immunization with complexed antigens, three additional and unrelated antigens, bovine serum albumin (BSA), horseradish peroxidase (HRP) and glucose oxidase (GOX) im comparative experiments. from Aspergillus niger are used Present findings show a close correlation between an increased number of germinal centers in lymph nodes, as well as their earlier appearance and rapid proliferation of cellular elements, and the appearance of serum antibody. Germinal centers show both an increase in number and proliferate faster when mice are immunized with complexes of antigen and antibody as compared with the same amount of antigen only. Immune defects in so-called immphologic deficiency syndromes in man may result from developmental disorders of immunologically active tissues, Developmental failure of lymphoid tissues may result in a functional deficiency, absence of one or more immunoglobulins, and in morphologically detectable defects. Although germinal centers contain immunoglobulins as shown by immunofluorescent methods, it is apparent that most immunoglobulins lie on the surface of cells or in reticulum cells within germinal centers. Present findings with HRP antigen provide evidence for antibody formation by lymphoid germinal. center cells as well as persistence of antigen and/or HRP-antibody complexes between dendritic reticular cells. : Increasing emphasis will be given to primary immunization with antigenantibody complexes prepared with gammaimmunoglobulins (IgG). Complexes of tetanus toxoid and specific human IgG have been prepared for primary immunization studies in man. The long-range purpose of this research is to | extend the principles of enhanced immunization demonstrated with the present complexed antigens to situations where antigens of bacterial, viral, protozoan. and parasitic origin are poorly antigenic. Previous work in this laboratory has demonstrated an increased susceptibility of irradiated animals to fatal anaphylactic shock. Since enhanced antibody responses are obtained in both normal and irradiated mice immunized with antigen-antibody complexes, the anaphylactogenic properties of complexes will be explored when complexes are prepared in antigen excess, equivalence, and antibody excess, The scope of this research has been enlarged to include a study of the In collaborcontrol of antibody responses in many strains of mice. genegite atiogswith the Jackson Laboratory, Bar Harbor, Maine, more than 140 strains of miceSiteh known genetic constitutions are being made available at no expense. The retative capacity of these various strains of mice to produce primary and secondary tetanus antitoxin responses is being tested. When significant differences in antibody responses are observed, The Jackson Laboratory will develop new recombinant inbred lines for immunologic studies. Immunogenetics has a direct bearing on the genetic control of the gene locus involved in the (See Continuation Sheet) 1119269 RX-176