THE REACTIVATION OF THE IMMUNE RESPONSE IN IMMUNOLOGICALLY SUPPRESSED ANIMALS
Attempts were made to restore antibody production in x-irradiated rats and in rabbits made tolerant to protein antigen by 6-mercaptopurine. A restorative factor from normal spleen cells was analyzed, and the kinetics of restoration, mainly in x-irradiated rats, were studied. Rats, aged 21/2 to 31/2 months, were used in most of the x-irradiation experiments, and sheep red blood cells were used as the test antigen. X irradiation of rats was carried out in most experinents with a total-body dose of 550 r given at a dose rate of 56 r/min. In some experiments the rats were exposed to 500 r. Injections of antigens and the cellular preparations in the reactivation experiments were carried out 24 hr after x irradiation. The cell suspensions were obtained by mechanical dissocation of spleen, liver, regenerating liver (six days after hepatectomy), and thymus. Evaluation of the restoration of agglutinin production in x- irradiated rats showed that normal rat spleen injected with the antigen restored the immune response and that the agglutinins obtained represented antibody formation by the irradiated recipient cells. The restoration was manifested in a shortening of the lag period and in incidence of reactive animals. The restorative activity resides in spleen cell nuclei, spleen DNA, and DNase-treated DNA. Studies of changes of DNA content of spleens of irradiated and reactivated animals and of the histologic picture of such spleens indicate that the restorative factors do not elicit a general nonspecific regeneration of the depleted cell population of the antibody-forming organs. Restoration, obtained by similar methods, was also studied in rabbits made tolerant to human serum albumin by 6-mercaptopurine treatment. After a discussion of the results in relation to the clonal concept of antibody formation and suppression, it was concluded that immunologic unresponsiveness is not a result of elimination of immunologically reactive cells but of the presence of nonreactive cells. Two alternative hypotheses are considered: the elective theory, which postulates that every cell is genetically predetermined to form every type of antibody; and the instructive theories of antibody production. Available data favors the elective theory, it is suggested. (BBB)
- Research Organization:
- Weizmann Inst. of Science, Rehovoth, Israel
- NSA Number:
- NSA-18-019722
- OSTI ID:
- 4023041
- Journal Information:
- Sym. Fundamental Cancer Res., 16th, Houston, 1962, Other Information: Orig. Receipt Date: 31-DEC-64
- Country of Publication:
- Country unknown/Code not available
- Language:
- English
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Related Subjects
AGE
AGGLUTININS
ANIMAL CELLS
ANTIBODIES
ANTIGENS
BODY
CELL NUCLEI
CYTOLOGY
DNA
DRUGS
ENZYMES
ERYTHROCYTES
HETEROCYCLICS
IMMUNITY
IRRADIATION
LIVER
NUCLEIC ACIDS
ORGANIC NITROGEN COMPOUNDS
ORGANIC SULFUR COMPOUNDS
PERFORMANCE
PHYSIOLOGY
PRECIPITATION
PREPARATION
PROTEINS
PURINES
RABBITS
RADIATION DOSES
RADIATION EFFECTS
RATS
RECOVERY
REGENERATION
SENSITIVITY
SPLEEN
SUSPENSIONS
TESTING
THYMUS
TISSUES
VARIATIONS
X RADIATION