scholarly journals STUDIES ON THE MECHANISM OF FEVER ACCOMPANYING DELAYED HYPERSENSITIVITY

1972 ◽  
Vol 135 (5) ◽  
pp. 1113-1132 ◽  
Author(s):  
Elisha Atkins ◽  
Joseph D. Feldman ◽  
Lorraine Francis ◽  
Ellen Hursh
Keyword(s):  
Serum Albumin ◽  
Lymph Nodes ◽  
Specific Antigen ◽  
In Vitro Release ◽  
Biologically Active ◽  
Delayed Hypersensitivity ◽  
Normal Blood ◽  
Blood Leukocytes ◽  
Draining Lymph Nodes

Experiments have been carried out to investigate the possible role of the sensitized lymphocyte in mediating the fevers of delayed hypersensitivity. Rabbits were made delayed hypersensitive to one of several heterologous proteins (bovine gamma globulin, bovine serum albumin, or human serum albumin) by footpad injection of antigen or antigen conjugated with dinitrophenol and incorporated in complete Freund's adjuvant. At intervals after sensitization, various tissues were removed, and single cell suspensions were incubated overnight with either carrier protein or conjugate in vitro. Release of an endogenous pyrogen (EP) was assayed by intravenous injection of the supernatant fluid into unsensitized rabbits. Of the tissues tested only those containing both lymphocytes and pyrogen-producing cells, blood, spleen, and draining lymph nodes, released detectable amounts of EP when incubated with antigen in vitro. Incubation of normal blood cells with specifically sensitized lymphocytes and antigen also resulted in significant release of pyrogen. Similarly, blood leukocytes released EP in vitro after mixture with supernates derived from incubation of sensitized lymphocytes and antigen. Cells and supernatant fluids from draining lymph nodes were usually effective in activating normal blood leukocytes earlier after sensitization than were those from mesenteric lymph nodes, suggesting that such cells, or antigen, had migrated from the original site of sensitization. The activator was soluble, nonpyrogenic in the dosages tested, and required incubation of viable cells with specific antigen for its production. These properties suggest that it may belong to the class of "lymphokines," biologically active agents released from lymphocytes that have been activated by immunologic or certain nonimmunologic stimuli.

scholarly journals HETEROGENEITY OF ANTIBODY-FORMING CELLS

1969 ◽  
Vol 129 (5) ◽  
pp. 1029-1044 ◽  
Author(s):  
Cesare Bosman ◽  
Joseph D. Feldman ◽  
Edgar Pick
Keyword(s):  
Lymph Nodes ◽  
Plasma Cells ◽  
Specific Antigen ◽  
Cell Suspensions ◽  
Electron Microscopic ◽  
Cytoplasmic Vacuoles ◽  
Draining Lymph Nodes

Cell suspensions from draining lymph nodes of immune and nonimmune rats were reacted in vitro with 125I-labeled antigens. In light microscopic radioautographs of smears, 17% of the immunized cells were tagged by specific antigen; 2.0% of control cells were positive. In electron microscopic radioautographs, 90% of the labeled elements from immune donors were lymphocytes, blast and plasma cells; 10% were monocytes-macrophages or other elements, including naked nuclei. 15% of the labeled cells from control materials were lymphocytes and plasma cells, while 85% were monocytes-macrophages and naked nuclei. Within cell suspensions derived from immunized animals there were almost twice as many lymphocytes marked by isotope as plasma cells, and the lymphocytes ranged in morphology from mature monoribosomal elements to immature polyribosomal cells. Antibody-forming cells fixed labeled antigen at their surfaces. The monocyte-macrophage class was distinguished by a high mean grain count and by distribution of grains within cytoplasmic vacuoles and lysosomes.

scholarly journals Indigenous enteric eosinophils control DCs to initiate a primary Th2 immune response in vivo

2014 ◽  
Vol 211 (8) ◽  
pp. 1657-1672 ◽  
Author(s):  
Derek K. Chu ◽  
Rodrigo Jimenez-Saiz ◽  
Christopher P. Verschoor ◽  
Tina D. Walker ◽  
Susanna Goncharova ◽  
...  
Keyword(s):  
Lymph Nodes ◽  
Eosinophil Peroxidase ◽  
Th2 Immune Response ◽  
Intestinal Immune System ◽  
Eosinophil Activation ◽  
And Migration ◽  
Deficient Mice ◽  
Draining Lymph Nodes

Eosinophils natively inhabit the small intestine, but a functional role for them there has remained elusive. Here, we show that eosinophil-deficient mice were protected from induction of Th2-mediated peanut food allergy and anaphylaxis, and Th2 priming was restored by reconstitution with il4+/+ or il4−/− eosinophils. Eosinophils controlled CD103+ dendritic cell (DC) activation and migration from the intestine to draining lymph nodes, events necessary for Th2 priming. Eosinophil activation in vitro and in vivo led to degranulation of eosinophil peroxidase, a granule protein whose enzymatic activity promoted DC activation in mice and humans in vitro, and intestinal and extraintestinal mouse DC activation and mobilization to lymph nodes in vivo. Further, eosinophil peroxidase enhanced responses to ovalbumin seen after immunization. Thus, eosinophils can be critical contributors to the intestinal immune system, and granule-mediated shaping of DC responses can promote both intestinal and extraintestinal adaptive immunity.

scholarly journals CYTOTOXICITY MEDIATED BY SOLUBLE ANTIGEN AND LYMPHOCYTES IN DELAYED HYPERSENSITIVITY

1968 ◽  
Vol 128 (6) ◽  
pp. 1255-1265 ◽  
Author(s):  
Nancy H. Ruddle ◽  
Byron H. Waksman
Keyword(s):  
Lymph Node ◽  
Cytotoxic Effect ◽  
Specific Antigen ◽  
Delayed Hypersensitivity ◽  
Soluble Antigen ◽  
Heterologous Proteins ◽  
Rat Embryo ◽  
Protein Carrier ◽  
Lymph Node Cells

Damage of rat embryo fibroblasts in the presence of sensitized lymph node cells reacting with specific antigen was shown to be closely correlated with delayed hypersensitivity in the animals from which the lymph node cells were taken. The phenomenon was not correlated with Arthus reactivity. In. animals sensitized with picryl conjugates of ovalbumin or human serum albumin, skin reactivity and the in vitro cytotoxic effect could be elicited only with the homologous conjugate or the protein carrier alone and not with picryl conjugates of heterologous proteins. Lewis rats developed more intense delayed sensitivity than BN rats, and Lewis lymph node cells were correspondingly more effective in producing specific damage of both syngeneic and allogeneic fibroblasts.

scholarly journals Biomimetic Gradient Scaffolds Containing Hyaluronic Acid and Sr/Zn Folates for Osteochondral Tissue Engineering

Polymers ◽  
2021 ◽  
Vol 14 (1) ◽  
pp. 12
Author(s):  
Gerardo Asensio ◽  
Lorena Benito-Garzón ◽  
Rosa Ana Ramírez-Jiménez ◽  
Yasmina Guadilla ◽  
Julian Gonzalez-Rubio ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Hyaluronic Acid ◽  
Folic Acid ◽  
In Vitro Release ◽  
Biologically Active ◽  
Human Articular Cartilage ◽  
Promising Alternative ◽  
Osteochondral Tissue

Regenerative therapies based on tissue engineering are becoming the most promising alternative for the treatment of osteoarthritis and rheumatoid arthritis. However, regeneration of full-thickness articular osteochondral defects that reproduces the complexity of native cartilage and osteochondral interface still remains challenging. Hence, in this work, we present the fabrication, physic-chemical characterization, and in vitro and in vivo evaluation of biomimetic hierarchical scaffolds that mimic both the spatial organization and composition of cartilage and the osteochondral interface. The scaffold is composed of a composite porous support obtained by cryopolymerization of poly(ethylene glycol) dimethacrylate (PEGDMA) in the presence of biodegradable poly(D,L-lactide-co-glycolide) (PLGA), bioactive tricalcium phosphate β-TCP and the bone promoting strontium folate (SrFO), with a gradient biomimetic photo-polymerized methacrylated hyaluronic acid (HAMA) based hydrogel containing the bioactive zinc folic acid derivative (ZnFO). Microscopical analysis of hierarchical scaffolds showed an open interconnected porous open microstructure and the in vitro behaviour results indicated high swelling capacity with a sustained degradation rate. In vitro release studies during 3 weeks indicated the sustained leaching of bioactive compounds, i.e., Sr2+, Zn2+ and folic acid, within a biologically active range without negative effects on human osteoblast cells (hOBs) and human articular cartilage cells (hACs) cultures. In vitro co-cultures of hOBs and hACs revealed guided cell colonization and proliferation according to the matrix microstructure and composition. In vivo rabbit-condyle experiments in a critical-sized defect model showed the ability of the biomimetic scaffold to promote the regeneration of cartilage-like tissue over the scaffold and neoformation of osteochondral tissue.

scholarly journals THE X-Y-Z SCHEME OF IMMUNOCYTE MATURATION

1968 ◽  
Vol 128 (4) ◽  
pp. 715-728 ◽  
Author(s):  
Vera S. Byers ◽  
Eli E. Sercarz
Keyword(s):  
Bovine Serum Albumin ◽  
Antibody Response ◽  
Serum Albumin ◽  
Lymph Nodes ◽  
Bovine Serum ◽  
Antibody Formation ◽  
Memory Cell ◽  
Secondary Response ◽  
Antigen Concentration

A concentration of 5 mg/ml bovine serum albumin (BSA) prevents the in vitro elicitation of a secondary response in primed rabbit popliteal lymph nodes, if it is left in contact with the node fragments for the first 6 days of culture. No antibody formation can be detected at any time during the culture period in most cases, although occasional fragments are resistant to inhibition. Reducing the exposure time to the first 3 days of culture delays the peak of the antibody response. The inhibition is antigen specific. Reconstruction experiments demonstrate that the inhibition is not due to antigen masking of the antibody. Even shortly after optimal stimulation, the addition of 5 mg/ml BSA to the fragments was not able to prevent a normal antibody response. The implications of these findings are that (a) a high antigen concentration suspends the memory cell in a reversibly paralyzed state, (b) memory cells have a heterogeneous susceptibility to inhibition, (c) once induced, the antibody response cannot be inhibited by antigen overloading, (d) unresponsiveness in a primed animal can be due to either exhaustion of the memory cell population or paralysis of the memory cell.

scholarly journals THE IN VITRO DESENSITIZATION OF SENSITIVE CELLS BY TRYPSIN

1964 ◽  
Vol 120 (6) ◽  
pp. 1189-1200 ◽  
Author(s):  
John R. David ◽  
H. S. Lawrence ◽  
L. Thomas
Keyword(s):  
Trypsin Inhibitor ◽  
Specific Antigen ◽  
Peritoneal Exudate ◽  
Soybean Trypsin Inhibitor ◽  
Delayed Hypersensitivity ◽  
Peritoneal Exudate Cells ◽  
Peritoneal Cells

Peritoneal exudate cells from animals exhibiting delayed hypersensitivity are inhibited from migrating in vitro by specific antigen. This inhibition is completely abolished by pretreatment of the sensitive cells with trypsin. The action of trypsin is prevented by soybean trypsin inhibitor. The results of experiments with mixtures of normal and sensitive cells suggest that trypsin alters an immunologic capacity of the sensitive cells. Trypsinized sensitive cells are capable of passively transferring delayed hypersensitivity and peritoneal cells taken from recipient animals are inhibited from migrating in vitro by specific antigen. These results suggest that the cells rapidly resynthesize the material removed by trypsin. The possible nature of the material removed by trypsin is discussed.

scholarly journals SUPPRESSION OF DELAYED HYPERSENSITIVITY IN VITRO BY INHIBITION OF PROTEIN SYNTHESIS

1965 ◽  
Vol 122 (6) ◽  
pp. 1125-1134 ◽  
Author(s):  
John R. David
Keyword(s):  
Protein Synthesis ◽  
Culture Medium ◽  
Specific Antigen ◽  
Delayed Hypersensitivity ◽  
Cell Protein ◽  
Sensitive Cell ◽  
Active Protein ◽  
Inhibit Protein Synthesis ◽  
Inhibition Of Protein Synthesis

Peritoneal cells from guinea pigs exhibiting delayed hypersensitivity are inhibited from migrating in vitro by specific antigen. This inhibition is prevented by the addition of puromycin to the culture medium. The amount of puromycin necessary to prevent the inhibition by antigen also suppressed the incorporation of C14-leucine into peritoneal cell protein. Additional evidence that the action of puromycin is due to its inhibition of protein synthesis has been obtained with analogues of puromycin; those that inhibit protein synthesis also prevent the action of antigen on the cells, while those analogues that do not inhibit protein synthesis have no effect. Actinomycin also prevents the inhibition of sensitive cells by antigen while chloramphenicol has no effect. The data indicate that the inhibition of sensitive cell migration by antigen requires active protein synthesis. The possible mechanisms by which inhibition of protein synthesis may influence the in vitro reactions of delayed hypersensitivity are discussed.

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