scholarly journals DELAYED HYPERSENSITIVITY

1957 ◽  
Vol 105 (1) ◽  
pp. 1-9 ◽  
Author(s):  
Jonathan W. Uhr ◽  
A. M. Pappenheimer ◽  
M. Yoneda
Keyword(s):  
Guinea Pigs ◽  
Diphtheria Toxin ◽  
Intradermal Injection ◽  
Delayed Hypersensitivity ◽  
Toxigenic Strain ◽  
Skin Reactions ◽  
Minute Amount ◽  
Initial Infection ◽  
Toxigenic Strains

Guinea pigs infected by intradermal injection of living toxigenic diphtheria bacilli and protected by horse antitoxic globulin, given either before or after infection, develop delayed hypersensitivity of the tuberculin type to diphtherial proteins. The highest degree of hypersensitivity is specifically directed against diphtheria toxin (or toxoid) itself, although smaller delayed skin reactions may be evoked in sensitized animals by other diphtherial proteins common to both toxigenic and non-toxigenic strains. Animals sensitized to diphtheria toxin by infection with a toxigenic strain in this way react positively to the Schick test and their serum usually contains no detectable antitoxin 2 to 3 weeks after the initial infection. Animals infected with living non-toxigenic diphtheria bacilli become sensitized to proteins common to both toxigenic and non-toxigenic strains but do not show sensitivity to toxin. The observations suggest that a minute amount of toxoid, or of toxin comparable to that which might be liberated during infection, might induce the hypersensitive state if injected in the form of a complex with excess antitoxin. This prediction is verified by the results reported in the following paper (23).

scholarly journals TRANSFER OF DELAYED HYPERSENSITIVITY TO DIPHTHERIA TOXIN IN MAN

1956 ◽  
Vol 104 (3) ◽  
pp. 321-336 ◽  
Author(s):  
H. S. Lawrence ◽  
A. M. Pappenheimer
Keyword(s):  
Transfer Factor ◽  
Peripheral Blood ◽  
Diphtheria Toxin ◽  
Intradermal Injection ◽  
Diphtheria Toxoid ◽  
Delayed Hypersensitivity ◽  
Skin Reactions ◽  
Mild Conditions ◽  
Highly Sensitive ◽  
Simultaneous Transfer

Simultaneous transfer of delayed hypersensitivity to diphtheria toxin and to tuberculin has been accomplished in eight consecutive instances in man using extracts from washed leucocytes taken from the peripheral blood of tuberculin-positive, Schick-negative donors who were highly sensitive (i.e., pseudoreactors) to purified diphtheria toxin and toxoid. The leucocyte extracts used for transfer contained no detectable antitoxin. The recipient subjects were Schick-positive (<0.001 unit antitoxin per ml. serum) and tuberculin-negative at the time of transfer. All the recipients remained Schick-positive for at least 2 weeks following transfer and in every case their serum contained less than 0.001 units antitoxin at the time when they exhibited maximal skin reactivity to toxoid. Evidence is presented which indicates that the transfer factor may be released from leucocyte suspensions under mild conditions in which most of the cells appear to remain morphologically intact. Four adult Schick-positive subjects have been sensitized to diphtheria toxoid by intradermal injection of a few micrograms of purified toxoid in the form of a washed toxoid-antitoxin precipitate. Two of these sensitized individuals showed severe delayed skin reactions specifically directed against diphtheria toxin (or toxoid) at a time when their serum antitoxin level was less than 0.001 units/ml.

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 STUDIES OF DELAYED HYPERSENSITIVITY IN VITRO

1957 ◽  
Vol 106 (1) ◽  
pp. 45-52 ◽  
Author(s):  
Lowell A. Glasgow ◽  
Herbert R. Morgan
Keyword(s):  
Skin Reaction ◽  
Guinea Pigs ◽  
Viral Antigen ◽  
Intradermal Injection ◽  
Mumps Virus ◽  
Delayed Hypersensitivity ◽  
Virus Infections ◽  
Splenic Macrophages

Guinea pigs experimentally infected with mumps virus develop a delayed, hypersensitive skin reaction following the intradermal injection of heat-inactivated mumps virus. This in vivo hypersensitivity is accompanied by a state of cellular hypersensitivity which can be demonstrated in vitro by the addition of mumps viral antigen to cultures of splenic macrophages, following which they become less motile and undergo lysis. These observations support the hypothesis that the state of hypersensitivity which develops early in mumps virus infections may have a role in the pathogenesis of the disease.

scholarly journals STUDIES ON DELAYED HYPERSENSITIVITY

1965 ◽  
Vol 121 (6) ◽  
pp. 873-888 ◽  
Author(s):  
Bernard B. Levine
Keyword(s):  
Guinea Pig ◽  
Guinea Pigs ◽  
Antigenic Determinant ◽  
Cross Reactivity ◽  
Delayed Hypersensitivity ◽  
Hypersensitivity Reactions ◽  
Binding Affinities ◽  
Structural Adaptation ◽  
Skin Reactions ◽  
High Binding

Experiments carried out with several well defined antigenic systems (hapten conjugates of poly-L-lysine and guinea pig serum albumin) in guinea pigs demonstrated that: 1. Arthus reactions also manifest carrier specificity, although to a smaller extent than do delayed hypersensitivity reactions. 2. Desensitization by injection of minute doses of antigen results in moderate specific desensitization of delayed hypersensitivity without desensitization of Arthus reactivity to the same antigenic determinant. 3. Insoluble antigen-antibody complexes prepared from high affinity guinea pig antibodies can elicit specific delayed skin reactions in sensitized guinea pigs. 4. Homologous conjugates of structurally similar haptens show considerably less cross-reactivity in delayed reactions than in immediate hypersensitivity reactions to the same antigenic determinant. These experimental results are interpreted as indicating that delayed hypersensitivity reactions in the guinea pig are mediated by "antibodies" of comparatively high binding affinities. High binding affinities are achieved for these antibodies more likely by closer structural adaptation between antigen and antibody than by a larger area of specific contact.

scholarly journals DELAYED HYPERSENSITIVITY

1957 ◽  
Vol 105 (1) ◽  
pp. 11-24 ◽  
Author(s):  
Jonathan W. Uhr ◽  
S. B. Salvin ◽  
A. M. Pappenheimer
Keyword(s):  
Guinea Pig ◽  
Guinea Pigs ◽  
Intradermal Injection ◽  
Delayed Hypersensitivity ◽  
Protein Antigens ◽  
Single Protein ◽  
Maximal Sensitivity ◽  
Degree Of Sensitization ◽  
Circulating Antibody ◽  
General Method

A general method for induction of the delayed hypersensitive state directed against single protein antigens is described. The method consists of intradermal injection of minute amounts of washed immune precipitates containing the antigen in question. Provided the specific precipitates are formed in the region of antibody excess, maximal sensitivity develops at least 2 to 3 weeks before detectable circulating antibody is formed in guinea pigs against the sensitizing antigen. Neither adjuvant nor killed acid-fast bacteria are required for induction of the delayed hypersensitive state although the degree of sensitization is considerably increased when the sensitizing material is incorporated in Freund's complete adjuvant. Characteristics of the "delayed" as opposed to the "immediate" hypersensitive states in the guinea pig are described and implications of the findings are discussed.

scholarly journals Hapten-specific delayed hypersensitivity to epsilon-2,4-dinitrophenyl-L-lysine-Ficoll in guinea pigs immunized with 2,4-dinitrophenyl-keyhole limpet hemocyanin.

1977 ◽  
Vol 145 (5) ◽  
pp. 1101-1114 ◽  
Author(s):  
P R McMaster ◽  
J D Owens ◽  
H F Dvorak ◽  
R Weichbrod ◽  
R Asofsky
Keyword(s):  
Skin Reaction ◽  
Guinea Pigs ◽  
Polymorphonuclear Leukocytes ◽  
Keyhole Limpet Hemocyanin ◽  
Active Immunization ◽  
Delayed Hypersensitivity ◽  
Delayed Reaction ◽  
Skin Reactions ◽  
Pale Pink ◽  
Erythematous Skin

After active immunization with 2,4-dinitrophenyl-keyhole limpet hemocyanin (DNP-KLH), 2,4-dinitropheynl-L-lysine (DNPL)-Ficoll may elicit indurated, erythematous skin reactions lasting 24-72 h. Histological sections of these reactions, examined by microscope techniques, showed they contained polymorphonuclear leukocytes and perivascularly situated lymphocytes and macrophages, but had very few basophils. Consequently, the reaction was interpreted as having an immediate component and a component typical of delayed hypersensitivity; this indicated that the delayed reaction could be specific for the DNP hapten. Although this delayed type of skin reaction was not transferred to recipients with anti-DNP-KLH serum, one pool of that serum did sensitize guinea pigs so that they could respond with a different skin reaction after challenge with DNPL-Ficoll. This reaction was soft, pale pink, and lasted for 24 h. Histologically, it contained only a few polymorphonuclear leukocytes. It differed from the delayed reaction in actively immunized animals in that it lacked induration, and was devoid of lymphocytes and macrophages.

Demonstration of delayed hypersensitivity to Neisseria meningitidis

1973 ◽  
Vol 19 (12) ◽  
pp. 1473-1479 ◽  
Author(s):  
James F. Pribnow ◽  
Diana J. Besemer ◽  
Joan M. Hall ◽  
Neylan A. Vedros
Keyword(s):  
Cell Wall ◽  
Lymph Node ◽  
Neisseria Meningitidis ◽  
Guinea Pigs ◽  
Capillary Tube ◽  
Delayed Hypersensitivity ◽  
Somatic Antigen ◽  
Skin Reactions ◽  
Cell Wall Preparation ◽  
Lymph Node Cells

Guinea pigs were sensitized to Neisseria meningitidis group A by subcutaneous injection of viable meningococci. The animals were skin-tested with heat-killed N. meningitidis, a cell wall preparation of N. meningitidis, and a soluble somatic antigen prepared from the meningococci. Control skin-test substances included heat-killed Neisseria gonorrhoeae, heat-killed Escherichia coli, purified protein derivative, and Hank's balanced salt solution. Positive 24-h skin reactions, characterized by induration that measured greater than 5 × 5 mm (25 mm2), were produced only by heat-killed meningococci and with the cell wall preparations. The soluble somatic antigen produced only erythema. The meningococci also caused inhibition of migration of macrophages when peritoneal cells from the sensitized guinea pigs were used in the capillary tube MIF test. No inhibition of migration was produced with the control antigens. The delayed hypersensitivity was transferred with viable lymph node cells from the sensitized guinea pigs, but not with dead lymph node cells or with serum. The tests will be used to determine whether rabbits injected intravitreally with N. meningitidis develop delayed hypersensitivity.

scholarly journals THE BACTERIAL INDUCTION OF HOMOGRAFT SENSITIVITY

1969 ◽  
Vol 129 (4) ◽  
pp. 623-645 ◽  
Author(s):  
Felix T. Rapaport ◽  
A. S. Markowitz ◽  
Robert T. McCluskey
Keyword(s):  
Guinea Pigs ◽  
Intradermal Injection ◽  
Mammalian Host ◽  
Skin Reactions ◽  
Skin Allografts ◽  
Hemorrhagic Necrosis ◽  
Combined Use ◽  
Group A ◽  
Membrane Antigens ◽  
Group Distribution

Immunization of rabbits with Group A Type 12 streptococcal cell membranes has elicited serum antibodies which have the ability to cause rapid rejection of skin allografts in guinea pigs. Intradermal injection of such antisera has resulted in skin reactions characterized by prominent polymorphonuclear leukocyte infiltrates, similar to those noted in the Arthus reaction. The combined use of membrane antisera and epinephrine has resulted in hemorrhagic necrosis of the skin of guinea pigs. The ability of membrane antisera to exert these effects appears to be dependent upon the presence in the host tissues of antigen(s) shared by or cross-reacting with streptococcal membrane antigens. Such cross-reacting antigens may have a group distribution in the outbred guinea pig population. The results highlight the potential biological importance of antigens present in the Group A streptococcal membrane in the induction of altered tissue reactivity in the mammalian host.

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.

Rabbit Skin Test for Estimation of T-2 Toxin and Other Skin-Irritating Toxins in Contaminated Corn

1974 ◽  
Vol 57 (5) ◽  
pp. 1121-1127 ◽  
Author(s):  
Choong W Chung ◽  
Mary W Trucksess ◽  
Albert L Giles ◽  
Leonard Friedman
Keyword(s):  
Guinea Pigs ◽  
Intradermal Injection ◽  
Young Rabbit ◽  
Skin Reactions ◽  
Rabbit Skin ◽  
Large Numbers ◽  
Graded Response ◽  
Weanling Rats ◽  
Field Samples ◽  
Intradermal Route

Abstract A rabbit bioassay test has been developed which can be used for screening large numbers of field samples of corn for T-2 and other toxins. Two μl each of the control solutions, 0.005–0.12 μg standards, and about 12 samples in ethyl acetate were applied simultaneously to the closely clipped skin of a 2–3 kg young rabbit. The skin reactions were read at 24, 48, and 72 hr. The prominent features of the reactions were erythema, edema, and necrosis. The T-2 toxin equivalences of the samples were estimated by the degree of the skin reactions caused by the standards. The method is reliable to at least 0.01 μg/test or 50 ppb. Graded response to the toxin is dependent upon the use of sensitive animals and properly diluted samples and standards. Rabbits were more sensitive than weanling rats or young guinea pigs, and the method showed better reproducibility with rabbits. Citrinin and zearalenone (F-2) showed negative skin reactions when applied at a level of 20 μg/skin site. They also showed poor skin reactions when administered by intradermal injection into rabbit skin. However, all 3 mycotoxins showed distinct skin reactions in guinea pigs by the intradermal route. The test was as sensitive as the topical test using rabbits with T-2 toxin. The prominent feature of the skin reaction was induration.

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