Joanne Finstad

Interactions between endotoxic lipopolysaccharides and the complement system in the sera of lower vertebrates.

Summary Endotoxic lipopolysaccharides (LPS) have potent ability to consume complement (C) components and generate biologically active peptides from the C system in normal mammalian serum. The present investigation shows that LPS derived from Escherichia coli has potent ability to consume hemolytic C in all vertebrate species in which C activity is detectable, including species as low phylogenetically as representative Chon-drichthyes (horned shark, nurse shark), Os-teichthyes (paddlensh, carp), Amphibia (bull frog, marine frog), and Reptilia (cobra, turtle). Hence, the consumption of C components in response to this ubiquitous bacterial product is a characteristic of vertebrate serum virtually throughout vertebrate evolution.

THE THYMUS IN IMMUNOBIOLOGY: WITH SPECIAL REFERENCE TO AUTOIMMUNE DISEASE*

The thymus has become a subject of intense interest and activity in biology and in clinical medicine in recent years.’ However, interest in the thymus is not only of recent origin. Indeed, many outstanding investigations were carried out on this organ before the turn of the century. Viewed in the perspective of our current knowledge, some of the earlier investigations were most incisive and contributory. Perhaps, unfortunately, these observations captured the imagination of certain clinicians and the concept of status thymicolymphaticus evolved. In retrospect, it would seem that this concept, erroneous in substance, set back investigations on the thymus. Thus, for a period, studies of the thymus seem to have fallen into disrepute. During the thirties and forties few significant contributions were made. Consequently, we feel it is entirely appropriate that a t least some of the energies for the current surge of study, investigations and enthusiasm for the thymus should have derived from the clinic.’ ” The authors hope in this publication to show tha t already the intensive laboratory effort is having a positive feedback to the clinic and already may be making contributions to our understanding of clinical disease. Our interest in the thymus in Minneapolis developed in 1953 when Good and Varco‘.’ had the opportunity to investigate an unusual person, a man who had severe deficiency of his immunological reactions and lacked gamma globulin. He had apparently developed this deficiency during adult life and could be defined as one of the patients with “acquired agammaglobulinemia.” An interesting aspect of this patient was that he also suffered from rheumatoid arthritis of a moderately severe type. He had developed this combination of diseases in apparent temporal association with the development of a huge tumor in the anterior chest. This huge mass in the mediastinum turned out to be a benign thymoma which was composed almost entirely of epithelial and stromal cells. I t seemed to us unusual that two such rare diseases as benign

Specific Immunoglobulin Synthesis in Lower Vertebrates Lacking Germinal Centers

The lymphoid system and capability for adaptive immune responses evolved in the lower vertebrates. We have previously defined adaptive immune responsiveness as ability to: make specific antibody, show immunologic memory upon repeated injection of antigen, reject homografts of skin or scale, exhibit second-set rejection reaction, and show proliferation of cells involved in the immune response [1, 2, 3, 4, 5].

The Development of Lymphoid Systems: Immune Response and Radiation Sensitivity in Lower Vertebrates

Extensive prior investigations have revealed that certain mammalian lymphocytes are extraordinarily susceptible to irradiation [1, 2], Other lymphoid cells show considerably greater resistance to destructive effects both of ionizing irradiation and of certain alkylating agents [3, 4, 5, 6, 7]. Among the cells known to be highly susceptible to irradiation are mammalian small lymphocytes, including lymphocytes residing within the thymus.

The Amphibian as a Key Step in the Evolution of Lymphoid Tissue and Diverse Immunoglobulin Classes

Numerous studies have revealed that the lymphoid tissue of the chicken comprises two distinct peripheral components with basically separate functions. If newly hatched chicks are subjected to complete extirpation of the bursa of Fabricius plus near lethal total body irradiation, these chickens grow up as immunological cripples unable to produce demonstrable amounts of circulating antibodies (1, 2). Such chickens lack both of the known immunoglobulins, IgM and IgG. Nevertheless, even though grossly defective in ability to synthesize antibody and gamma globulin, such chickens have normal or essentially normal ability to develop and express cell-mediated immunity. In contrast, chickens subjected to total body irradiation and complete thymic extirpation grow up as immunological cripples unable to execute the cell-mediated immunities; i.e., delayed allergy, homograft immunity, and capacity to execute the graft-versus-host reactions. This division of immunological functions on the basis of influence of two separate central lymphoid organs is reflected in specialization of structure in the peripheral lymphoid organs; e.g., spleen, lymph nodes, skin, and intestinal lymphoid aggregates. Chickens irradiated and bursectomized in the newly hatched period completely lack plasma cells and germinal centers, but possess normal numbers of circulating small lymphocytes and normal aggregates of lymphocytes in the spleen, lymph nodes and other lymphoid cell organs and tissues. The thymus-dependent lymphocyte population is responsible for the cell-mediated immune reaction while the bursa-dependent germinal centers and plasma cells are responsible for the synthesis of immunoglobulin and antibody.

Influence of aldosterone and angiotensin II on endotoxin shock in the primate.

Summary Severe endotoxin shock in monkeys resulted in hypotension, oliguria or anuria, hyperkalemia and death. No characteristic electrocardiographic findings were elicited. Aldosterone and angiotensin II were employed alone and in combination in attempts to reverse the shock. The most favorable results were obtained with a combination of the steroid and pressor drug. As in canine endotoxin shock, aldosterone markedly potentiated the pressor action of angiotensin II. Optimum results were correlated with the amount of aldosterone administered.