scholarly journals DELAYED HYPERSENSITIVITY

1958 ◽  
Vol 108 (6) ◽  
pp. 891-904 ◽  
Author(s):  
Jonathan W. Uhr ◽  
A. M. Pappenheimer ◽  

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.

1966 ◽  
Vol 123 (2) ◽  
pp. 267-281 ◽  
Author(s):  
John E. Coe ◽  
Joseph D. Feldman ◽  
Sun Lee

Delayed hypersensitivity was produced in donor Lewis rats by sensitization with soluble protein antigens emulsified in complete Freund's adjuvant. Cells of their thoracic duct lymph were collected for varying periods of time and transferred intravenously to isogenic Lewis recipients. With this model the following conclusions were reached: 1. Delayed hypersensitivity was transferred by thoracic duct cells. 2. The longer the drainage of the thoracic duct, the fewer cells were needed to achieve a successful transfer. With continuing drainage the proportion of small lymphocytes decreased and large cells increased. There was, therefore, a better correlation between successful transfer of delayed hypersensitivity and the number of large cells transfused than between positive skin reactions and transfer of small lymphocytes. 3. Prolonged fistula of the thoracic duct did not diminish the skin reaction of sensitized donors to specific antigen. 4. Delayed hypersensitivity was elicited in recipients 3 wk after transfer of sensitized cells. There was evidence that delayed hypersensitivity was enhanced in recipients, possibly because of prior skin testing. 5. Total body X-irradiation abolished the lesions of passively transferred delayed hypersensitivity. Recovery of positive skin tests was observed 19 to 20 days later. 6. The lesions of delayed hypersensitivity were probably mediated by cells. There was no evidence that a circulating high affinity antibody played a role in this type of immunologic reaction.


1964 ◽  
Vol 119 (5) ◽  
pp. 851-868 ◽  
Author(s):  
S. B. Salvin ◽  
R. F. Smith

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.


1957 ◽  
Vol 105 (1) ◽  
pp. 1-9 ◽  
Author(s):  
Jonathan W. Uhr ◽  
A. M. Pappenheimer ◽  
M. Yoneda

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).


1971 ◽  
Vol 134 (5) ◽  
pp. 1144-1154 ◽  
Author(s):  
David G. Tubergen ◽  
Joseph D. Feldman

Adoptive transfer experiments were performed to define the immunological role of thymus and bone marrow cells in the induction of delayed hypersensitivity (DH). The results indicated the following, (a) Bone marrow from immune donors contained cells capable of being stimulated by antigen to initiate the expression of DH. (b) Bone marrow from nonimmune or tolerant donors contained cells that were needed to complete the expression of DH after the infusion of immune lymph node cells. (c) Normal bone marrow and thymus cells cooperated in the irradiated recipient to induce the most vigorous skin reactions to specific antigen; these reactions were seen only when the recipients were stimulated by antigen. Either cell type alone was ineffective. (d) In the presence of tolerant bone marrow cells, thymus cells from immune donors gave a more vigorous response than did thymus cells from normal or tolerant donors. (e) There was suggestive evidence that thymus cells were the source of trigger elements that initiated DH. (f) Antigen in the irradiated recipient was necessary to induce DH after infusion of bone marrow cells alone, or bone marrow and thymus cells together.


PEDIATRICS ◽  
1966 ◽  
Vol 37 (5) ◽  
pp. 776-786
Author(s):  
J. Shuster ◽  
Z. Hart ◽  
C. W. Stimson ◽  
A. J. Brough ◽  
M. D. Poulik

Two patients with ataxia telangiectasia were studied. There is absence of γA immunoglobulin, poor delayed hypersensitivity skin reactions, and abnormal rejection of skin grafts. The susceptibility to sinopulmonary infections is probably related to the abnormal cellular and circulating antibody responses which these patients demonstrate. Experimental evidence indicates that the fundamental immunologic defect in this disease lies in thymus gland. The etiology of the neurologic abnormalities is unknown. The first instance of a cerebellar tumor to develop in this syndrome is reported.


1958 ◽  
Vol 107 (1) ◽  
pp. 109-124 ◽  
Author(s):  
S. B. Salvin ◽  

Guinea pigs were injected in the footpads with either purified diphtheria toxoid or recrystallized egg albumin in Freund adjuvant without mycobacteria. Each guinea pig was then skin-tested only once with the specific antigen and bled for antibody determination. After injection of the sensitizing antigen, a latent period occurred during which neither sensitivity nor circulating antibody could be detected. A period of delayed sensitivity followed wherein circulating antibody could not be discerned and which could be transferred by lymph node cells. Ultimately, the Arthus type sensitivity developed, accompanied by circulating antibody. The duration and severity of reactions to homologous antigens during the last 2 phases varied with the antigen and with the dose. An increase in the sensitizing dose decreased the duration of the delayed type of allergy, a decrease in the dose prolonged the delayed type. Inclusion of mycobacterium in the sensitizing inoculum tended to introduce delayed sensitivity earlier and delay the onset of Arthus type sensitivity. When specific precipitate in antibody excess was included with the toxoid in the sensitizing dose, the onset of the Arthus phase was hastened. When lymph nodes from a large number of sensitized donors were removed during the latter part of the latent period, recipients of the cells showed a delayed type sensitivity.


1958 ◽  
Vol 108 (6) ◽  
pp. 905-924 ◽  
Author(s):  
Jonathan W. Uhr ◽  
M. W. Brandriss

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.


1998 ◽  
Vol 66 (8) ◽  
pp. 3606-3610 ◽  
Author(s):  
Konstantin Lyashchenko ◽  
Claudia Manca ◽  
Roberto Colangeli ◽  
Anna Heijbel ◽  
Alan Williams ◽  
...  

ABSTRACT The tuberculin skin test currently used to diagnose infection withMycobacterium tuberculosis has poor diagnostic value, especially in geographic areas where the prevalence of tuberculosis is low or where the environmental burden of saprophytic, nontuberculous mycobacteria is high. Inaccuracy of the tuberculin skin test often reflects a low diagnostic specificity due to the presence in tuberculin of antigens shared by many mycobacterial species. Thus, a skin test specific for tuberculosis requires the development of new tuberculins consisting of antigens specific to M. tuberculosis. We have formulated cocktails of two to eight antigens of M. tuberculosis purified from recombinant Escherichia coli. Multiantigen cocktails were evaluated by skin testing guinea pigs sensitized with M. bovis BCG. Reactivity of multiantigen cocktails was greater than that of any single antigen. Cocktail activity increased with the number of antigens in the cocktail even when the same amount of total protein was used for cocktails and for each single antigen. A cocktail of four purified antigens specific for the M. tuberculosis complex elicited skin test responses only in BCG-immunized guinea pigs, not in control animals immunized with M. avium. These findings open the way to designing a multiantigen formulation for a skin test specific for tuberculosis.


1953 ◽  
Vol 98 (5) ◽  
pp. 451-460 ◽  
Author(s):  
L. A. Sternberger ◽  
Frank Maltaner ◽  
Jacob DeWeerdt

Immune sera were subjected to treatment with alkali in the cold to cause dissociation of antigen-antibody complexes. Precipitates and a capacity to fix complement developed in some of these sera subsequent to such treatment. The specific immunologic nature of these phenomena and their observation in relation to disappearance of free antigen and appearance of free antibody in circulation are discussed. The phenomena observed appear to be consistent with the assumption that a circulating antibody-antigen complex is revealed as a result of treatment.


1936 ◽  
Vol 64 (4) ◽  
pp. 657-672 ◽  
Author(s):  
Marion C. Morris

It has been shown that antianaphylaxis is not caused by a partial saturation of cellular or humoral antibodies by the following facts. 1. Guinea pigs passively sensitized with anti-horse or antipneumococcus serum and specifically desensitized do not manifest as great a reactivity upon resensitization with the same antiserum as upon the original sensitization. 2. Guinea pigs passively sensitized with anti-Friedländer Type B serum or antipneumococcus Type II serum and specifically desensitized do not attain the same degree of reactivity as normal animals when passively sensitized with anti-horse serum. 3. Guinea pigs passively sensitized with anti-Friedländer Type B serum and desensitized with the specific carbohydrate remain as resistant to infection with Friedlander's bacillus Type B as undesensitized guinea pigs. Since in this case, at least, it is agreed that type-specific immunity and type-specific hypersensitiveness are due to the same type-specific antibody, a change in anaphylactic response should be accompanied by a change in immune response, provided this change depends on antibody balance. 4. A determination of the antibody content of the serum of sensitized as well as of desensitized guinea pigs by mouse protection tests indicates that a loss of reactivity in desensitized animals cannot be adequately accounted for on the basis of depletion of circulating antibody. These experiments suggest that hypersensitiveness and resistance are different manifestations of the same antigen-antibody reaction while antianaphylaxis is a state of refractoriness which is due neither to excess of circulating antibody nor to antibody depletion, but is the result of secondary changes the true nature of which is still not definitely established.


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