scholarly journals SPECIFICITY OF PASSIVELY TRANSFERRED DELAYED HYPERSENSITIVITY

1963 ◽  
Vol 118 (3) ◽  
pp. 341-352 ◽  
Author(s):  
John S. Najarian ◽  
Joseph D. Feldman
Keyword(s):  
Skin Lesion ◽  
Guinea Pigs ◽  
Specific Antigen ◽  
Test Site ◽  
Total Radioactivity ◽  
Lymphoid Cells ◽  
Delayed Hypersensitivity ◽  
Specific Test ◽  
Autoradiographic Analysis ◽  
Reciprocal Arrangement

Guinea pigs were injected intravenously with lymphoid cells sensitized to tubercle bacilli (TBC cells) and with lymphoid cells sensitized by contact to a simple chemical, dinitrofluorobenzene (DNFB cells). In each transfer, either the TBC cells or the DNFB cells were labeled with H3-thymidine. Immediately after transfusion, each recipient was skin tested with PPD and DNFB. 24 hours later these lesions were removed for determination of total radioactivity and for autoradiographic analysis. When TBC cells labeled with H3-thymidine were transferred with DNFB cells without an isotopic marker, the total radioactivity and the concentration per gram of skin lesion were greater in the PPD test sites. In the reciprocal arrangement, when DNFB cells labeled with H3-thymidine were transfused with TBC cells without an isotopic tag, the total radioactivity and the concentration per gram of skin lesion were greater in the DNFB test site. Similar results were obtained in guinea pigs which were actively immunized by tubercle bacilli and passively by transfer of DNFB cells. Autoradiographic analysis of test sites from guinea pigs passively transferred with both types of sensitized cells confirmed these findings. By calculation, only a very small number of transferred sensitized cells reached the specific test lesion. Most of the cellular infiltrate was derived from the responding host. The specificity of the reaction of delayed hypersensitivity was apparently achieved by retention of the sensitized cells after they had arrived by chance at the specific antigen depot and was not due to a non-specific stickiness of sensitized or inflamed lymphoid cells.

scholarly journals DELAYED HYPERSENSITIVITY

1958 ◽  
Vol 108 (6) ◽  
pp. 905-924 ◽  
Author(s):  
Jonathan W. Uhr ◽  
M. W. Brandriss
Keyword(s):  
Guinea Pigs ◽  
Serum Antibody ◽  
Specific Antigen ◽  
Endotoxin Tolerance ◽  
Delayed Hypersensitivity ◽  
Febrile Response ◽  
Protein Antigens ◽  
Skin Reactivity ◽  
Highly Sensitive ◽  
Specific Challenge

Guinea pigs with delayed hypersensitivity to protein antigens show a specific febrile response accompanied by a lymphopenia following injection of a desensitizing dose of specific antigen. No signs of shock are observed in highly sensitive animals following this injection. The response is not prevented in sensitive guinea pigs by inducing endotoxin tolerance or by pretreating with cortisone before specific challenge. Using a suitable antigen in sufficiently sensitive animals as little as 100 µg. can elicit a pronounced febrile response. Injection of a desensitizing dose of antigen specifically abolishes systemic as well as skin reactivity for several days. Normal or hypersensitive (delayed-type) animals passively sensitized with sufficient amounts of serum antibody show hypothermia after specific challenge and may show a delayed type of fatal shock. Differences were noted between their systemic reactivities, however, and the reactivity seen in specifically challenged tuberculous animals.

scholarly journals PASSIVE TRANSFER OF TUBERCULIN SENSITIVITY BY TRITIATED THYMIDINE-LABELED LYMPHOID CELLS

1961 ◽  
Vol 114 (5) ◽  
pp. 779-790 ◽  
Author(s):  
John S. Najarian ◽  
Joseph D. Feldman
Keyword(s):  
Tritiated Thymidine ◽  
Specific Antigen ◽  
Test Site ◽  
Passive Transfer ◽  
Lymphoid Cells ◽  
Skin Tests ◽  
Skin Reactions ◽  
Positive Skin ◽  
Spleen And Lymph Nodes ◽  
Immature Cells

Passive transfer of tritiated thymidine-labeled BCG sensitized lymphoid cells into homologous guinea pigs resulted in positive tuberculin skin reactions 24 hours after testing with PPD. Labeled cells were found specifically attracted to these sites. Labeled non-sensitized lymphoid cells did not appear at PPD injection sites, nor did labeled sensitized cells accumulate in non-specific inflammatory lesions. The specifically reacting tritiated cells were small, medium, and large lymphocytes and stem or immature cells of the lymphoid series. In the homologous system employed, positive skin tests were either minimal or absent 3 days after transfusion of activated cells. The injected labeled sensitized cells were rapidly cleared from the circulating blood and lodged in the lungs, spleen, and lymph nodes. Upon application of specific antigen they reappeared at the skin test site at 6 hours and then increased in number for the next 18 hours.

scholarly journals STUDIES ON NORMAL AND IMMUNE LYMPHOCYTE TRANSFER REACTIONS IN GUINEA PIGS, WITH SPECIAL REFERENCE TO THE CELLULAR CONTRIBUTION OF THE HOST

1972 ◽  
Vol 136 (6) ◽  
pp. 1545-1563 ◽  
Author(s):  
Siraik Zakarian ◽  
R. E. Billingham
Keyword(s):  
Guinea Pigs ◽  
Significant Proportion ◽  
Intradermal Injection ◽  
Lymphoid Cells ◽  
Delayed Hypersensitivity ◽  
F1 Hybrids ◽  
Genetic Constitution ◽  
F1 Hybrid ◽  
Immune Lymphocyte ◽  
Lymphocyte Transfer

Using guinea pigs of strains 2 and 13 and their F1 hybrids as experimental subjects, various lines of evidence have been obtained that in this species, as in all others tested, the only significant cellular antigens with which donor lymphocytes engage when normal and immune lymphocyte reactions are incited are radiosensitive leukocytes. Constitutive cells of the skin are unimportant. (a) The intensities of these reactions in irradiated subjects are dependent upon the peripheral leukocyte concentration. When this falls below a certain threshold no reactions are incitable. (b) Highly leukopenic animals are capable of developing immune lymphocyte transfer (ILT) reactions if normal lymphoid cells of their own genetic constitution are mixed with the putative attacking donor cells, as "supplementing antigen," before inoculation. (c) Radiation-chimeric strain 13 animals having F1 hybrid leukocytes in their bloodstream give typical ILT reactions when challenged intradermally with strain 13 anti-2 node cells. Exposure of strain 2 animals to 600 R does not prevent their becoming actively immunized if, 24 hr later, they are injected intradermally with strain 13 lymphocytes. However, this sensitization, revealed by the host's capacity to give delayed hypersensitivity reactions, wanes as leukopenia progresses. On the basis of this and other findings it is argued that the flare-up stage of the NLT reaction in preirradiated hosts is mainly an expression of host sensitivity against the transferred alien cells. Two unexpected observations have been made in the course of this study: (a) F1 hybrid animals developed what appeared to be a strong delayed hypersensitivity after intradermal inoculation with parental strain lymphoid cells or antigenic extracts prepared from them. (b) If strain 13 guinea pigs which had been sensitized against strain 2 tissue antigens by intradermal injection of lymphocytes 7 days beforehand were inoculated intravenously with strain 2 antigenic extract a significant proportion of the animals developed severe delayed necrotizing reactions, recall flares, at some or all of the healed skin inoculation sites.

scholarly journals HETEROGENEITY OF THE CELLULAR IMMUNE RESPONSE

1971 ◽  
Vol 133 (2) ◽  
pp. 187-201 ◽  
Author(s):  
Robert C. Bast ◽  
Eleanor J. Manseau ◽  
Harold F. Dvorak
Keyword(s):  
Immune Response ◽  
Cellular Immune Response ◽  
Large Population ◽  
Specific Antigen ◽  
Lymphoid Cells ◽  
Lymphocyte Stimulation ◽  
Delayed Hypersensitivity ◽  
Skin Reactions ◽  
Cellular Immune

Lymph node cells from guinea pigs immunized with HSA in complete Freund's adjuvant were grown in cultures containing different concentrations of specific antigen. Stimulation of thymidine incorporation was induced with progressively lower concentrations of HSA at successive intervals after sensitization. Moreover, the intensity of delayed skin reactions and the magnitude of stimulation in vitro increased over the same interval. These events are considered compatible with an evolution of the cellular immune response resulting from the selection of lymphoid cells by decreasing concentrations of antigen in vivo. Cells from animals rendered tolerant to HSA failed to respond to specific antigen in culture. As tolerance waned, stimulation was achieved at high but not low antigen concentrations. Tolerance, measured by cutaneous reactivity or by lymphocyte stimulation, was less readily induced in animals sensitized with adjuvant containing a reduced concentration of mycobacteria. Lymph nodes from these animals contained a large population of cells reactive at high antigen concentration, presumably less susceptible to the toleragenic effect of intravenous antigen. The dissociation of delayed hypersensitivity and antibody formation observed early in the immune response and upon recovery from tolerance has permitted correlation of lymphocyte stimulation with delayed hypersensitivity and cutaneous basophil hypersensitivity respectively.

scholarly journals PASSIVE TRANSFER OF TRANSPLANTATION IMMUNITY

1963 ◽  
Vol 117 (3) ◽  
pp. 449-456 ◽  
Author(s):  
John S. Najarian ◽  
Joseph D. Feldman
Keyword(s):  
Skin Graft ◽  
Guinea Pigs ◽  
Tritiated Thymidine ◽  
Specific Antigen ◽  
Passive Transfer ◽  
Lymphoid Cells ◽  
Transplantation Immunity ◽  
Tuberculin Sensitivity

Passive transfer of transplantation immunity was accomplished in inbred guinea pigs with tritiated thymidine-labeled lymphoid cells sensitized to homologous tissues. Autoradiographs of the homologous skin graft sites disclosed the presence of relatively few or no labeled cells at the site of rejection. Passive transfer of transplantation immunity was also accomplished with sensitized lymphoid cells enclosed in cell-impenetrable Millipore chambers. Previous studies with passive transfer of tuberculin sensitivity in guinea pigs revealed that the specifically sensitized cells could be easily found at the site of challenge in the presence of specific antigen and were ineffective when enclosed in Millipore chambers. It appeared, then, that the homograft reaction and delayed sensitivity of tuberculin type were achieved by different immunologic mechanisms within the same species.

scholarly journals LYMPHOID CELLS IN DELAYED HYPERSENSITIVITY

1972 ◽  
Vol 135 (4) ◽  
pp. 985-996 ◽  
Author(s):  
S. B. Salvin ◽  
J. Nishio
Keyword(s):  
Skin Reaction ◽  
Adoptive Transfer ◽  
Migration Inhibitory Factor ◽  
Skin Testing ◽  
Specific Antigen ◽  
Lymphoid Cells ◽  
Delayed Hypersensitivity ◽  
Skin Response ◽  
X Irradiation

X-irradiation up to 480 R does not inhibit either adoptive transfer of delayed hypersensitivity or production in vitro of soluble mediators, such as migration-inhibitory factor (MIF). Above that dosage and as high as 3000 R, adoptive transfer is inhibited, but production of MIF is not. An increase in skin response occurred when 24–48 hr were allowed to elapse after intravenous transfer and before skin testing. Treatment of recipients with colchicine at the time of adoptive transfer inhibited the development of a skin reaction to specific antigen.

scholarly journals DELAYED HYPERSENSITIVITY

1958 ◽  
Vol 108 (6) ◽  
pp. 891-904 ◽  
Author(s):  
Jonathan W. Uhr ◽  
A. M. Pappenheimer ◽  
Keyword(s):  
Guinea Pigs ◽  
Single Injection ◽  
Skin Testing ◽  
Specific Antigen ◽  
Delayed Hypersensitivity ◽  
Skin Reactions ◽  
Antibody Complex ◽  
Antigen Antibody ◽  
Free Antigen ◽  
Circulating Antibody

Guinea pigs rendered hypersensitive (delayed-type) to protein antigen can be completely and specifically desensitized by a single injection containing a sufficient amount of the corresponding antigen. Although 1 to 2 mg. of specific antigen are required for complete desensitization, as little as 20 µg. suffices to decrease the size of specific skin reactions in sensitized animals. The duration of non-reactivity lengthens as the amount of antigen in the desensitizing injection is increased, but skin reactivity eventually returns and is accompanied by the appearance of excess circulating antibody. Desensitization can be accomplished with the antigen-antibody complex as well as by "free" antigen. The appearance of delayed skin reactions can be prevented in fully sensitized animals by intravenous desensitization 2 or more hours after intradermal challenge or by simply skin testing with a desensitizing dose of specific antigen. Injection of a desensitizing dose of antigen into specifically sensitized animals also results in a transient anergic state, the implications of which are discussed.

scholarly journals THE SPECIFICITY OF ALLERGIC REACTIONS

1964 ◽  
Vol 119 (5) ◽  
pp. 851-868 ◽  
Author(s):  
S. B. Salvin ◽  
R. F. Smith
Keyword(s):  
Guinea Pigs ◽  
Intraperitoneal Injection ◽  
Heterologous Protein ◽  
Gamma Globulin ◽  
Specific Antigen ◽  
Delayed Hypersensitivity ◽  
Allergic Reactions ◽  
Aminobenzoic Acid ◽  
Protein Conjugate ◽  
Circulating Antibody

Adult guinea pigs were made unresponsive to a heterologous protein (e.g. bovine gamma globulin, or BGG) or a hapten-protein conjugate (e.g. p-aminobenzoic acid-bovine gamma globulin, or PABAγmiddot;BGG) by intraperitoneal injection of 80 mg cyclophosphamide and the specific antigen. This immunologic unresponsiveness developed to the specific antigen administered simultaneously with the cyclophosphamide, and not to any variants. Thus, animals unresponsive to PABAγmiddot;BGG remained unresponsive to the original antigen on challenge with a variant, but formed delayed hypersensitivity and circulating antibody to the variant. The specificity of immunologic unresponsiveness, therefore, seems more closely related to the whole antigen molecule than does delayed hypersensitivity.

Passive Transfer of Delayed Hypersensitivity to 2,4-Dinitrochlorobenzene in Guinea Pigs with Leucocytic Extracts.

1954 ◽  
Vol 86 (2) ◽  
pp. 251-253 ◽  
Author(s):  
W. S. Jeter ◽  
M. M. Tremaine ◽  
P. M. Seebohm
Keyword(s):  
Guinea Pigs ◽  
Passive Transfer ◽  
Delayed Hypersensitivity

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

1968 ◽  
Vol 128 (6) ◽  
pp. 1237-1254 ◽  
Author(s):  
Nancy H. Ruddle ◽  
Byron H. Waksman
Keyword(s):  
Lymph Node ◽  
Genetic Difference ◽  
Specific Antigen ◽  
Delayed Hypersensitivity ◽  
Target Cells ◽  
Soluble Antigen ◽  
Rat Embryo ◽  
Egg Albumin ◽  
Lymph Node Cells ◽  
Electronic Particle Counter

In the presence of specific antigen, lymph node cells from inbred rats with delayed hypersensitivity to tuberculoprotein, bovine gammaglobulin, and egg albumin produced progressive destruction of monolayers of rat embryo fibroblasts in tissue culture, first apparent at 48 hr and maximal at 72 hr. The effect was specific and did not depend on a genetic difference between the lymph node cells and target cells. It required antigen concentrations equal to or greater than 1.25 µg/ml and lymphocyte: target cell ratios of approximately 10 or 20:1. It could be evaluated both by a plaquing technique and by cell enumeration with an electronic particle counter.

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