Variability of natural killer cell activity in anuran amphibians.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to E L Cooper.
Explore the source record for details and available documents.
We have previously shown that social confrontation between aggressive fish (e.g., Tilapia) produces a suppression of several immunological parameters--nonspecific cytotoxicity and mitogen-stimulated proliferation in pronephric leukocytes--in the subordinate fish. By using the opioid antagonist, naltrexone, we now demonstrate indirectly that this immunosuppression is in part mediated by the endogenous opioid system. Evidence is presented that naltrexone-mediated reversal of immunosuppression may be limited to the populations of the cytotoxic and T-cell lineages. The proliferation response to lipopolysaccharide is unaffected by naltrexone. Our data also demonstrate that serum from subordinate (immunosuppressed) fish is immunosuppressive in normal fish--an effect that can be reversed by naltrexone. These results support a link between the neuroendocrine and immune systems in fish, the lowest vertebrate.
To test the hypothesis that there are circannual differences in mitotic activity in males and females, normal human peripheral blood lymphocytes were stimulated with suboptimal concentrations of Phytohemagglutinin (PHA), Concanavalin A (Con A) and Poke weed mitogen (PWM) over two summer/winter cycles. Lymphocyte responses for the entire population were significantly higher in the summer than in the winter. The same results were observed when responses were compared between a summer and a successive winter. However, when male and child-bearing age female responses were compared, females showed a higher significant difference for PHA and Con A between summer and winter, but not for PWM. These different responses due to season may reflect a relationship between the neuroendocrine and immune systems. At the cell level, these results suggest that an inherent difference exists between female and male lymphocytes and that these lymphocytes are sensitive to seasonal changes.
Explore the source record for details and available documents.
Exposure of C. lazera to sublethal concentrations of the molluscicide, Bayluscide, for a 6-month period induced 14% (0.1 ppm) and 95% (0.3 ppm) mortalities. In addition, there was a depletion of hemopoeitic tissue in the mesonephros and spleen, an increased susceptibility to pathogens and appearance of nodules containing infectious organisms. Surviving fish produced lower titers of antibodies against injected antigens than controls and the number of corpuscles of Stannius increased in proportion to the concentration and duration of exposure to the Bayluscide. Long term exposure probably induced immunosuppression in C. lazera which caused these changes.
Natural agglutinins against human, guinea pig, and rat erythrocytes (RBC) and bacteria Bacillus thuringiensis were readily detected in hemolymph of final instar larvae with resulting titers of 0-9 (log2). Titers were independent of sex and season but varied conspicuously and reproducibly with age. Moreover, response of hemagglutinins to heating varied with age being heat-labile in younger larvae, yet totally resistant to heating for 30 min at 70 degrees C in older ones. Bacterial agglutinins were uniformly resistant at all larval ages. The study thus reveals that the amounts and physico-chemical properties of P. ricini agglutinins change with larval development. Therefore, larval age should be taken into close consideration before reporting on the occurrence and properties of agglutinins in insects.
Leukocytes of the earthworm, Lumbricus terrestris, secrete agglutinins in vitro, as shown by measuring agglutinin titers of the culture medium and by observing secretory rosette formation by leukocytes with erythrocytes. Leukocytes form the highest percentages of secretory rosettes with rabbit erythrocytes (RBC) and with other RBC species in the order: rat, guinea pig, mouse, calf, sheep, horse, goat. Leukocytes displayed allotypic specificity by forming rosettes selectively with erythrocytes from different individual rabbits. Eight sugars inhibited rosette formation, along with the polysaccharide mannan and the glycoproteins thyroglobulin and bovine submaxillary mucin. Cyclohexamide did not affect rosette formation, suggesting that agglutinins may be preformed and stored in leukocytes prior to secretion. Leukocytes also formed E-type rosettes with erythrocytes, but apparently utilized different receptors from those of secretory rosettes since they were not inhibited by the same sugars.
Our earlier observations revealed that social stress causes drastic effects on different physiological mechanisms and degenerative changes in leucocytes. In this preliminary work, we analyzed the effect of social aggressiveness on functional activities of leucocytes emphasizing (NCC) activity in Tilapia. At 10 hr post stress induction, fish could be differentiated into three categories: 1) dominants; 2) subordinates; and 3) indeterminants. Results of NCC as indicated by 4 hr. 51Cr-release assay, demonstrated a significant suppression in cytotoxic reactivity in the subordinates and indeterminants compared to dominants. This suppression appears to be due to a decrease in the binding capacity of effector cells to YAC-1 target cells as indicated by the decreased number of conjugate forming cells. This binding process is a key event in activating the fish equivalent of NK cells in mammals. Decreased NCC-activity in stressed fish suggests that aberrations in cell mediated immunity result from social aggressiveness.
Substances known to inhibit mammalian NK cell activity during the first stage of lysis (i.e., effector cell-target cell binding) will also inhibit frog SK cell activity. We analyzed target cell lysis after conjugate formation between one target cell and at least one effector cell. Using frog SK effector cells and frog allogeneic and mammalian tumor target cells, we demonstrated that EDTA, the Ca+2 and Mg+2 chelating agent, but not EGTA, the Ca+2 chelating agent, inhibited binding. Thus, Mg+2 is required for conjugate formation. The inhibitory effects of EDTA were at least partially reversible following removal of EDTA. Binding also required membrane fluidity since pretreatment of targets with glutaraldehyde prevented effector cell binding. Adding glutaraldehyde after conjugate formation increased lysis. Modification of target cell surface proteins by DMSO and trypsin also inhibited binding of effector and target cells. Substances inhibiting binding decreased lysis as measured by 51Cr-release from target cells. Inhibition of binding between SK effector and target cells adds further support to our view that natural or spontaneous killing of foreign cells may be one of the most primitive immuno-defense mechanisms.
Explore the source record for details and available documents.
We present similarities between mammalian natural killer (NK) cells and (anuran amphibian) frog spontaneous killer (SK) cells. A cytotoxic assay utilizing allogeneic erythrocytes as target cells was used and lysis assessed by measuring release of hemoglobin. SK effector cells, just as mammalian NK cells, are not sensitive to cycloheximide nor most simple sugars (50 mM glucose, glucose-6-phosphate, galactose, fucose, mannose). However, SK activity is inhibited by chloroquine, colchicine and mannose-6-phosphate. When SK cells were co-incubated with mammalian tumor cells, they were able to lyse only the NK-sensitive target YAC-1, but not other mammalian tumor cell targets including K562, Molt-4, Raji, P815 and EL4. Lysis of YAC-1 cells was also inhibited by colchicine and chloroquine. These results allow speculation on the evolution of cell mediated cytotoxicity since natural cytotoxic cells are present in ectothermic vertebrates.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
The biological roles of invertebrate agglutinins have been and remain an unresolved subject of controversy. Classical studies on agglutinins, beginning with the pioneer work of Noguchi (1903) on Limulus polyphemus and Homarus americanus have emphasized their hemagglutinating properties, an approach that has been criticized for its lack of biological relevance. While erythrocyte agglutination has proven useful for determining various properties of invertebrate agglutinins, it does not address the question of their natural function. More recently, invertebrate agglutinins have been investigated for their ability to interact with pathogenic agents such as bacteria (for review, see Pistole, 1982), yeast (Van der Knapp et al., 1982; Renwrantz and Stahmer, 1983) and parasitic protozoans (Ingram et al., 1984). In addition, the possible relationship of agglutinins to defense mechanisms of both vertebrates and invertebrates has been indicated by the observation that limulin, the major agglutinin of Limulus polyphemus, bears a number of similarities to vertebrate C-reactive proteins (Robey and Liu, 1981). In annelids, there have been no studies on bacterial agglutinins prior to our work with Lumbricus (Stein et al., 1985; Stein et al., submitted). Earthworms are particularly appropriate for studying bacterial agglutinins since their coelomic fluid contains constant low levels of bacteria and fungal spores, and their agglutinins are both naturally occurring and inducible. Although our initial studies on Lumbricus agglutinins were directed toward their hemagglutinating properties, our recent observations using bacteria have allowed us to reach the following conclusions: 1) Lumbricus coelomic fluid normally contains agglutinins against both erythrocytes and bacteria. After injecting worms with either erythrocytes or bacteria, agglutinin titers increase in coelomic fluid. This increase appears to be due to both an increase in numbers of agglutinins as well as levels of specific agglutinins. 2) Absorption studies, temperature effects and sugar inhibition analyses suggest that agglutinins which bind to erythrocytes are identical to bacterial agglutinins, but there are additional agglutinins capable of reacting only with bacteria. 3) The inducibility and bacterial binding properties of Lumbricus agglutinins suggest that they serve an immune function by participating in the earthworm's defense against bacterial infection. In this sense, the agglutinins serve as a humoral surveillance system that entraps and prevents the multiplication of pathogenic bacteria.
Explore the source record for details and available documents.
Morphology and development of the thymus in fish Oryzias latipes was studied in response to corticosteroids. Adult fish were subjected to different concentrations of two corticosteroids, deoxycorticosterone acetate (DOCA) and cortisone acetate (CA). Histology of the thymus and thymocyte counts in treated fish were compared to normal ones. There was no change in histology of thymus due to CA treatment even those subjected to 10 mg/l water which is a lethal dose of DOCA. In contrast, the effect of DOCA at low doses (0.01 and 0.1 mg/l water) was examined and resulted in reduction of thymus volume due to depopulation of thymocytes from the entire gland. Thymus subjected to DOCA at a high dose (1 mg/l water) caused destruction of all thymocytes and reticular cells resulting in complete disappearance of the thymus. There was dose dependent mortality associated with DOCA. The maximum lethal dose was 10 mg/l causing death of all treated fish within a few hours. This information is relevant to the use of CS in fish therapy in response to stress.
This inclusive review describes essentially the findings of the author and his colleagues on the responses of earthworm coelomocytes to wounding and parasite infection and the responses of the earthworms themselves to second-set tissue grafts.