scholarly journals INDUCED UNRESPONSIVENESS TO SIMPLE ALLERGENIC CHEMICALS

1965 ◽  
Vol 121 (4) ◽  
pp. 591-606 ◽  
Author(s):  
Jack R. Battisto ◽  
Merrill W. Chase

Normal guinea pigs fed chemical haptens develop a specific state of unresponsiveness, inhibiting subsequent development of dermal sensitization with the same hapten and modifying profoundly the synthesis of anaphylactic antibody in response to hapten conjugated to guinea pig proteins. The degree of unresponsiveness has been tested by exposing hapten-fed animals to intense haptenic stimulation. Animals of groups that were demonstrably unresponsive to picryl chloride could be made to form hapten-specific antibody by injecting picrylated bovine gamma globulin. Specific anaphylactic-type antibodies, presumably 7S γ1, were synthesized, and in animals given PBGG adsorbed to alumina there arose a measurable concentration of precipitating antibody, presumably 7S γ2, perhaps slightly earlier than in similarly treated control animals. Attempts to impose contact-type reactivity on such unresponsive animals met with limited success. Injection of picrylated guinea pig erythrocyte stromata in a complete Freund's adjuvant, with subsequent applications of picryl chloride to the dermis, led to definite contact sensitivity to 0.3 per cent picryl chloride, whereas parallel treatment of normal control animals induced sensitivity to 0.006 or 0.002 per cent. By this double method of stimulation, hapten-fed animals did not advance in sensitivity by reason of the secondary dermal applications of the simple chemical, whereas control animals developed increasingly higher sensitivity by these contacts in what appeared to be a stepwise manner. Picryl chloride-fed guinea pigs injected intradermally with picryl chloride either after or before forming picryl-specific circulating antibody still remained unable to develop picryl-specific contact hypersensitivity. Control animals synthesizing picryl-specific antibody subsequently responded to intradermal injection of picryl chloride with contact-type sensitivity. Interpretations of these results are discussed and the view is presented that delayed-type hypersensitivity and circulating antibodies of the varieties measured here are formed independently of each other.

1963 ◽  
Vol 118 (6) ◽  
pp. 1021-1035 ◽  
Author(s):  
Jack R. Battisto ◽  
Merrill W. Chase

Guinea pigs fed picryl chloride to induce specific immunologic unresponsiveness cleared small amounts of venously infused antipicryl antibody at a rate equal to that of normal guinea pigs. Catabolism of passively administered picryl-specific antibody did not alter the unresponsive state of picryl chloride-fed guinea pigs or the responsive state of normal guinea pigs. Lymphoid cells of picryl chloride immunized guinea pigs produced equal amounts of picryl-specific antibody in picryl chloride-fed and normal animals. Allergen-fed guinea pigs remained unresponsive to attempted sensitization with the allergen in excess of 10 months after the final feeding, though some became feebly sensitive between 9 and 11 months. Second attempts to make unresponsive animals hypersensitive were unsuccessful. White blood cells of guinea pigs unresponsive to picryl chloride were unable to transfer delayed-type hypersensitivity for picryl chloride to normal recipients yet readily transferred tuberculin hypersensitivity.


1966 ◽  
Vol 124 (1) ◽  
pp. 69-80 ◽  
Author(s):  
Jerome R. Pomeranz ◽  
Philip S. Norman

Guinea pigs receiving one large dose of picryl chloride by the intravenous or oral routes commonly develop circulating antibody demonstrable by passive cutaneous anaphylaxis or by active anaphylaxis. They often concommittantly become unresponsive to the induction of delayed contact hypersensitivity by intracutaneous injections. Erythrocytes obtained from guinea pigs after infusion or feeding of picryl chloride may be used to sensitize other animals when injected with adjuvant. It is concluded that guinea pigs may be anaphylactically sensitized to simple chemicals by the intravenous and oral routes if a sufficient dose is administered.


1998 ◽  
Vol 66 (7) ◽  
pp. 3454-3456 ◽  
Author(s):  
Martin J. Elhay ◽  
Thomas Oettinger ◽  
Peter Andersen

ABSTRACT Two antigens from Mycobacterium tuberculosis, ESAT-6 and MPT64, elicited delayed-type hypersensitivity (DTH) skin responses in outbred guinea pigs infected with M. tuberculosis by the aerosol and intravenous routes but not those sensitized with M. bovis BCG or M. avium. The DTH epitope of ESAT-6 was mapped to the C terminus. Nonresponders to the individual antigens were found, but all animals responded to a combination of ESAT-6 and MPT64 or their respective minimal target peptides. Correspondingly, these molecules could form the basis of a new skin test for tuberculosis.


2010 ◽  
Vol 79 (2) ◽  
pp. 716-723 ◽  
Author(s):  
Hongliang Yang ◽  
JoLynn Troudt ◽  
Ajay Grover ◽  
Kimberly Arnett ◽  
Megan Lucas ◽  
...  

ABSTRACTPurified protein derivative (PPD) is a widely used reagent for the diagnosis ofMycobacterium tuberculosisinfection. Recently, the molecular composition of PPD was defined, with hundreds of mycobacterial protein representatives making up PPD. Which, if any, of these specific products drive the potency of PPD remains in question. In this study, two proteins (DnaK and GroEL2) previously identified as dominant proteins in PPD were tested for the capacity to induce delayed-type hypersensitivity (DTH) responses in H37Rv-infected or BCG-vaccinated guinea pigs. These two proteins were used in pull-down assays to identify interacting PPD products. Six proteins were identified as interacting partners with DnaK and GroEL2, i.e., Rv0009, Rv0475, Rv0569, Rv0685, Rv2626c, and Rv2632c. These six proteins were tested alone and in combination with DnaK and GroEL2 for the capacity to induce a DTH response in the guinea pig model. From these studies, two cocktails, DnaK/GroEL2/Rv0009 and DnaK/GroEL2/Rv0685, were found to induce DTH responses in H37Rv-infected or BCG-vaccinated guinea pigs that were indistinguishable from DTH responses driven by a PPD injection. The mechanism by which DTH responses were induced was elucidated by histologic examination, analysis of activated CD4+/CD8+T cells, and cytokine mRNA expression at the site of the DTH response. PPD and the protein cocktails tested induced strong DTH responses in H37Rv-infected guinea pigs. Ex vivo phenotyping of T cells at the DTH site indicated that this response is mediated by activated CD4+and CD8+T cells, with increases in gamma interferon and tumor necrosis factor alpha, but not interleukin-10, at the site of the DTH response. Our results demonstrate for the first time that the PPD response can be mimicked at the molecular level with defined protein cocktails. The use of this defined product will allow a more thorough understanding of the DTH response and may provide a platform for more rapid and sensitive second-generation skin test reagents for the diagnosis ofM. tuberculosisinfection.


1928 ◽  
Vol 47 (6) ◽  
pp. 987-991 ◽  
Author(s):  
Susan Griffith Ramsdell

The change in surface tension behavior in the serum of sensitized guinea pigs is, as du Noüy has concluded for immunized rabbit serum, not referable to an antibody content, since we know that the capacity for transfer of sensitization remains in the serum indefinitely, while the increased time-drop phenomenon is a transitory manifestation. That this phenomenon cannot be invoked by a new antigen capable of calling out its specific antibody would seem to make this response one due to some basic stable alteration of a tissue active in the general process of sensitization: That this alteration is not one called out by such a simple toxic injury as a uranium nitrate nephritis is contributory evidence that the primary toxicity of the horse serum is not the specific factor involved.


1936 ◽  
Vol 63 (4) ◽  
pp. 491-507 ◽  
Author(s):  
Louise Pearce ◽  
Paul D. Rosahn ◽  
Ch'uan-K'uei Hu

The white mouse, the guinea pig, the calf, and probably the rat, were found to be susceptible to infection with the virus of rabbit pox. Serial transmission of the virus in mice by brain to brain passage was characterized by a fatal outcome usually on the 5th or 6th day after inoculation. Infection of the guinea pig was accomplished by intratesticular injection and the virus was continued to the 2nd passage in this species. Guinea pigs developed a well marked cutaneous reaction from the intradermal injection of both rabbit and guinea pig tissue virus. Active virus was demonstrated in the testicles of rats 8 days after intratesticular injection by rabbit subinoculation. In the calf inoculation of the scarified skin was followed by the development of large papular lesions with marked hemorrhage and necrosis. The results of the investigations on the etiology of rabbit pox and of the experimentally induced infection reported in this and the four preceding papers (1–4) are discussed with special reference to the relation of pox virus to other viruses and of rabbit pox to other pock diseases.


1941 ◽  
Vol 73 (3) ◽  
pp. 431-438 ◽  
Author(s):  
K. Landsteiner ◽  
M. W. Chase

Experiments with guinea pigs are described which show that under special experimental conditions the intraperitoneal injection of conjugates made with homologous erythrocyte stromata leads to typical skin sensitization of the contact type towards the respective simple chemicals, namely picryl chloride or 2,4-dinitrofluorobenzene. Therefore such sensitivity can be brought about not only by low molecular chemical compounds but by a material which must be regarded as a typical antigen.


1960 ◽  
Vol 111 (2) ◽  
pp. 171-180 ◽  
Author(s):  
Cheng-Mei Shaw ◽  
Willson J. Fahlberg ◽  
Marian W. Kies ◽  
Ellsworth C. Alvord

The intradermal injection of aqueous solutions of certain homologous neural proteins will suppress the encephalomyelitis which is induced in guinea pigs by the previous injection of whole homologous brain with Freund's adjuvants. These neural proteins extracted by dilute acid from defatted guinea pig brain are themselves highly encephalitogenic when injected with adjuvants, but the specificity of this suppression for encephalitogenic as compared to non-encephalitogenic extracts remains to be proven. Suppression is probably not due to a non-specific stress reaction, as indicated by the absence of suppression by intradermal injections of alcohol and by statistically insignificant and inconstant effects of similar injections of tuberculin.


1958 ◽  
Vol 107 (1) ◽  
pp. 55-61 ◽  
Author(s):  
Robert A. Patnode ◽  
Paul C. Hudgins

The administration of triton WR-1339 (300 mg./kg. subcutaneously) to tuberculin-sensitive guinea pigs 2 hours before the intradermal injection of PPD depresses slightly their skin sensitivity to tuberculin and essentially obliterates the lytic effect of tuberculin on their circulating leucocytes. When leucocytes from tuberculin-sensitive guinea pigs are exposed to triton in vitro at a concentration level attainable in vivo the cells are partially protected against lysis by PPD.


2001 ◽  
Vol 280 (3) ◽  
pp. R908-R912 ◽  
Author(s):  
Leah D. Whigham ◽  
Ellen B. Cook ◽  
James L. Stahl ◽  
Ricardo Saban ◽  
Dale E. Bjorling ◽  
...  

Conjugated linoleic acid (CLA) has been shown to enhance immune reactions such as lymphocyte blastogenesis and delayed-type hypersensitivity. We investigated the role of CLA in type I (immediate) hypersensitivity, using a guinea pig tracheal superfusion model for measuring antigen-induced airway smooth muscle contraction and inflammatory mediator release. Female Hartley guinea pigs were fed a diet supplemented with 0.25 g corn oil or linoleic acid/100 g of diet (control) or 0.25 g CLA/100 g of diet for at least 1 wk before and during active sensitization to ovalbumin antigen. Tracheae from sensitized guinea pigs were suspended in air-filled water-jacketed (37°C) tissue chambers in a superfusion apparatus. Tracheae were superfused with buffer containing antigen, and tissue contraction was recorded. Superfusate was collected at 90-s intervals for evaluation of histamine and PGE2 release. CLA did not affect antigen-induced tracheal contractions when expressed as gram contraction per gram tissue. CLA significantly reduced antigen-induced histamine and PGE2 release. CLA appears to decrease release of some inflammatory mediators during type I hypersensitivity reactions.


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