M. G. Hanna

Effect of antigen dose on lymphatic tissue germinal center changes.

Summary Investigations were performed on the effect of various doses of sheep erythrocyte antigen on spleen germinal center changes. These changes were correlated with the production of specific serum antibody during the first 30 days after primary antigen stimulation. The results indicate a dose-response relationship between antigen dose and germinal center changes. A correlation was observed between the germinal center changes and specific serum antibody production.

Reduced Immune Potential of Aged Mice Significance of Morphologic Changes in Lymphatic Tissue.

Summary Hemagglutinin responding capacity to sheep erythrocyte antigen in 3-year-old BC3F1 mice was approximately 10% of the response in normal young adult mice. The reduction in primary antibody-forming capacity was determined in aged animals that had no specific lesion of lymphatic tissue such as lymphoma, lymphosarcoma, suggesting that the reduction was primarily due to unspecific atrophy or degenerative changes. Results of splenectomy in the aged mice suggest that the spleen is the major source of immunological competence in the aged animals and that the reduced immune capacity in these mice is not due simply to failing spleen function.

Efficacy of intralesional bcg therapy in guinea pigs with disseminated tumor

It has been previously demonstrated that transplanted syngeneic tumors established in the skin of inbred (strain‐2) guinea pigs regressed and regional lymph node metastases were eliminated after intralesional injection of viable Mycobacterium bovis (BCG). During the course of this reaction there is the development of tumor‐specific immunity. This experimental model was further manipulated in order that it would more closely approximate a clinical reality. In the present study an evaluation was made of the effectiveness of the developing tumor‐specific immunity in this BCG therapy model, to abrogate artifically induced distant tumor deposits and to assess the requirement for tumor‐specific immunity in the local BCG‐mediated tumor regression. During BCG‐mediated regression of established intradermal tumor, the developing tumor‐specific immunity inhibited the growth of artificially induced vascular metastases in animals receiving a 10* or 105 tumor cell dose. However, there is a direct causal relationship between the distant tumor burden and the escape of skin tumor and regional lymph node metastases from BCG‐mediated regression. Thus, multiple tumor deposits as low as 10* cells are capable of competing for or preempting tumor‐specific immune reactivity, which must be a requirement during some phase of the intralesional BCG‐mediated therapy of established tumor and regional lymph node metastases. Thus, a significant therapeutic effect could be achieved in guinea pigs with established skin tumors and limited vascular metastases when the modality of therapy included BCG intralesional injection, followed 6 weeks later by surgery of the treated skin tumor and regional lymph node.

Modulation of the Immune Response of Guinea Pigs by Repeated BCG Scarification

Summary Immune competence to sheep erythrocytes, skin allografts, and antigenic tumor transplants was studied in random-bred CFDH as well as inbred (syngeneic) strain-2 guinea pigs receiving repeated BCG scarification. Peripheral blood leucocyte (PBL) changes and histopathological alterations of the skin site and regional lymph nodes were also evaluated during the course of treatment. The results demonstrate that in this experimental model BCG scarification depresses humoral immune competence and augments cellular immunity. Elevation of the PBL counts was also indicative of an acute systemic effect resulting from repeated BCG treatment. Flaring of previous scarification sites, activation and enlargement of draining nodes, and progressive responsiveness of nodes draining sites of previous scarification were also observed.

Histoproliferative effect of rauscher leukemia virus on lymphatic tissue. II. Antigen-stimulated germfree and conventional balb/c mice.

Summary Normal and antigenically stimulated germfree BALB/c young adult mice were used as a test system for studying the role of the nonthymus-dependent and thymus-dependent lymphoid tissue in Rauscher leukemia virus infection. It was considered that the splenomegaly of Rauscher disease within a germfree population would be enhanced by the establishment of active germinal centers in the nonthymus-dependent region of the lymphatic nodules of mice previously immunized with sterile sheep erythrocytes (SRBC). Similar comparisons were made in conventional BALB/c mice in which SRBC and lactic dehydrogenase virus were used as the test antigens. Results of these studies demonstrate the necessary, if not essential, role of the antigen-retaining reticular cells and immunoblasts of lymphatic tissue germinal centers in the early lymphoblastosis and subsequent splenomegaly of Rauscher disease. In addition, morphologic results strongly suggest the differential effect of the Rauscher preparation on the thymus- and nonthymus-dependent regions of the lymphatic tissue.

A Comparative Study of the Immune Reaction in Germfree and Conventional Mice

In recent years considerable attention has been devoted to the germinal centers of lymphatic tissue, particularly as these structures relate to the immune reaction (see reviews by Thorbecke and Hurlimann, 1965, and Congdon and Hanna, 1967). Results of various studies have demonstrated 1) that an antigen-stimulated proliferation of large pyroninophilic cells occurs in germinal centers (Hanna, 1964; Cottier et al., 1967), and this proliferation is antigen dose dependent (Hanna et al., 1966); 2) that the sensitized immune cell compartment develops first in lymphatic nodules at the time of germinal center hyperplasia (Thorbecke et al., 1964); and 3) that during the course of an immune reaction, antigen is localized and retained extracellularly in plasma membrane infoldings of specialized reticular cells which constitute the fixed stroma of the germinal center (Szakal and Hanna, 1968, Nossal et al. , 1968).

TIME RELATIONSHIP OF INJECTION OF ACTINOMYCIN D AND ANTIGEN TO THE IMMUNE RESPONSE.

Summary Large basophilic cells in the lymphoid nodule of spleen are damaged when actinomycin D is given before, with, or after injection of sheep erythrocytes. The severity of cytotoxicity is dependent upon the time the drug is given in relation to injection of antigen. Consonant with the relative degree of damage is delay in appearance of circulating hemagglutinin. The time for injection of animals for maximal delay in appearance of hemagglutinin and coincident maximal cytotoxicity is 4 to 8 hours before injection of antigen.