130 The Lymphocyte and Lymphocytic Tissue 



of lymph nodes may be followed by lymphopenia and a decrease in size of 

 other lymph nodes. The question of indirect effects has been critically re- 

 viewed by several investigators' 10 who concluded that indirect effects have 

 not been definitely proved and are probably not an important factor. 



In this review I shall assume the point of view that the chief action of 

 x-rays on lymphoid tissue in vivo is twofold: (1) a direct, destructive action 

 on lymphocytes and (2) an inhibitory action on the production of these 

 cells. 



Under proper conditions four stages of reaction are observed in response 

 to irradiation: (1) an initial, acute destruction, (2) an abortive recovery, 

 (3) chronic lymphocytic depression, and (4) recovery. 



Initial Destructive Stage 



The early effects of irradiation on lymphocytes were studied by Ross, 

 Furth, and Bigelow 4 "' who collected the lymphatic fluid from the thoracic 

 duct of rats before and after irradiation. Three to eight hours after irradi- 

 ation of the whole animal with 750 r, the lymphcytes were found to have 

 various denegerative changes including small vacuoles in the nucleus and 

 cytoplasm, binucleated and multinucleated cells, cells with "lumped" 

 chromatin, and finally dead cells with pyknotic and fragmented nuclei. By 

 ten hours most of the injured cells and debris had disappeared, and the 

 number of lymphocytes were reduced. It would seem that most of the 

 lymphocytes died in vivo by the development of intranuclear vacuoles and 

 pyknosis. In addition, the binucleated and multinucleated cells and cells 

 with lumped chromatin may be cells that were dying by delayed fixation. 

 This and other studies indicate that irradiated lymphocytes undergo the 

 same two types of degenerative changes in vivo as in vitro, i.e., death by intra- 

 nuclear vacuolization and death by delayed fixation. 



Lymphoid Tissue. The first change in irradiated lymphoid tissue of 

 animals is degeneration and death of lymphocytes as indicated by pyknosis 

 and fragmentation of nuclei. This change is seen after total body irradia- 

 tion or after local irradiation of lymphoid tissue. Some of the degenerating 

 lymphocytes have intranuclear vacuoles. 1 ' 4S ' ,i4 Irradiation of rabbits and 

 other animals with 25 r produces a perceptible effect on lymph nodes. The 

 destruction of lymphocytes with the formation of cellular debris is seen 

 particularly in the secondary centers of lymphoid follicles of lymph nodes, 

 in the cortex of the thymus, and in the Malpighian bodies of the spleen. 

 A lesser amount of necrotic debris is seen in the medullary cords of lymph 

 nodes and in the medulla of the thymus. The dead cells and the cellular 

 debris arc rapidly phagocytized by macrophages. The debris-laden cells are 

 seen almost as soon as degeneration occurs and persist for about 24 hours in 

 the rabbit. 



