Abstract
In light of knowledge of the rate and route of dispersal of allergenic chemicals from ear sites (0.25 µg of picryl chloride, or 2:4 dinitrochlorobenzene in 0.25 µg and 5.0 µg amounts), dispersal was interrupted at selected times by ear excision. The animals exposed in this manner to different, tiny amounts of allergen were tested for development of contact type hypersensitivity. Both of these allergenic chemicals left the local ear site in about three phases of successively lengthening "half-lives." In the first phase, the escape rate was high. The principal pathway of escape was not via the lymphatics but via the blood vessels. Ear excisions made at 24 hr after injection of 0.25 µg of picryl chloride (PCl) or at 12 hr after injection of 5.0 µg of dinitrochlorobenzene (DNCB) essentially blocked onset of delayed type hypersensitivity, hence the first fraction to escape (80% of PCl, 98% of DNCB) was not used for sensitization. This large fraction serves rather to set up a state of specific tolerance, for these individuals showed extensive deficits in their ability to respond to a later sensitizing course. Also the ability to form hapten-specific antibody appeared nearly completely suppressed. Injections of allergen into the blood stream or directly in auricular nodes, in an amount approximating that which escaped early from the ear, also led to the same degrees of unresponsiveness—sometimes full, sometimes partial tolerance. The same types of specific tolerance were secured also by injecting subsensitizing doses into the ear, without excision, or into the flank and by contact tests applied to the flank. The allergen remaining in the ear after the early outflow, particularly between 12–24 hr and 3–4 days, appeared to constitute the sensitizing depot. The longer this depot was available to the animals the greater the immunological "information" for sensitization was picked up until the depot had served its full function around the 4th day. "Peripheral sensitization" was clearly demonstrable. The eventual degree of sensitivity attained by the animals was a resultant of two immunologic processes which occurred independently—tolerogenic effects of escaped chemical on the one hand and on the other the sensitizing effect of the local sensitizing depot of allergen bound in the ear tissue.
Full Text
The Full Text of this article is available as a PDF (1.1 MB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Asherson G. L. Selective and specific inhibition of 24-hour skin reactions in the guinea-pig. II. The mechanism of immune deviation. Immunology. 1966 Feb;10(2):179–186. [PMC free article] [PubMed] [Google Scholar]
- Asherson G. L., Stone S. H. Selective and specific inhibition of 24 hour skin reactions in the guinea-pig. I. Immune deviation: description of the phenomenon and the effect of splenectomy. Immunology. 1965 Sep;9(3):205–217. [PMC free article] [PubMed] [Google Scholar]
- BATTISTO J. R., CHASE M. W. IMMUNOLOGICAL UNRESPONSIVENESS TO SENSITIZATION WITH SIMPLE CHEMICAL COMPOUNDS; A SEARCH FOR ANTIBODY-ABSORBING DEPOTS OF ALLERGEN. J Exp Med. 1963 Dec 1;118:1021–1035. doi: 10.1084/jem.118.6.1021. [DOI] [PMC free article] [PubMed] [Google Scholar]
- BATTISTO J. R., CHASE M. W. INDUCED UNRESPONSIVENESS TO SIMPLE ALLERGENIC CHEMICALS. II. INDEPENDENCE OF DELAYED-TYPE HYPERSENSITIVITY AND FORMATION OF CIRCULATING ANTIBODY. J Exp Med. 1965 Apr 1;121:591–606. doi: 10.1084/jem.121.4.591. [DOI] [PMC free article] [PubMed] [Google Scholar]
- BATTISTO J. R., MILLER J. Immunological unresponsiveness produced in adult guinea pigs by parenteral introduction of minute quantities of hapten or protein antigen. Proc Soc Exp Biol Med. 1962 Oct;111:111–115. doi: 10.3181/00379727-111-27717. [DOI] [PubMed] [Google Scholar]
- CHASE M. W. Experimental sensitization with particular reference to picryl chloride. Int Arch Allergy Appl Immunol. 1954;5(2):163–191. doi: 10.1159/000228095. [DOI] [PubMed] [Google Scholar]
- CONVERSE J. M., BALLANTYNE D. L., Jr, WOISKY J. The vascularization of skin homografts and transplantation immunity. Ann N Y Acad Sci. 1958 Oct 7;73(3):693–697. doi: 10.1111/j.1749-6632.1959.tb40846.x. [DOI] [PubMed] [Google Scholar]
- Chase M. W. Hypersensitivity to simple chemicals. Harvey Lect. 1967;61:169–203. [PubMed] [Google Scholar]
- FREUND J., LIPTON M. M. Experimental allergic encephalomyelitis after the excision of the injection site of antigen-adjuvant emulsion. J Immunol. 1955 Dec;75(6):454–459. [PubMed] [Google Scholar]
- FREY J. R., WENK P. Experimental studies on the pathogenesis of contact eczema in the guinea-pig. Int Arch Allergy Appl Immunol. 1957;11(1-2):81–100. doi: 10.1159/000228405. [DOI] [PubMed] [Google Scholar]
- FREY J. R., WENK P. Experimentelle Untersuchungen zur Pathogenese des Kontaktekzems. Dermatologica. 1956 Apr-Jun;112(4-6):265–305. [PubMed] [Google Scholar]
- FREY J. R., WENK P. Uber die Funktion der regionalen Lymphknoten bei der Entstehung des Dinitrochlorbenzol-Kontaktekzems am Meerschweinchen. Dermatologica. 1958 Apr-May;116(4-5):243–259. [PubMed] [Google Scholar]
- LOWNEY E. D. TOPICAL HYPOSENSITIZATION OF ALLERGIC CONTACT SENSITIVITY IN THE GUINEA PIG. J Invest Dermatol. 1964 Dec;43:487–490. doi: 10.1038/jid.1964.190. [DOI] [PubMed] [Google Scholar]
- Landsteiner K., Chase M. W. STUDIES ON THE SENSITIZATION OF ANIMALS WITH SIMPLE CHEMICAL COMPOUNDS : VI. EXPERIMENTS ON THE SENSITIZATION OF GUINEA PIGS TO POISON IVY. J Exp Med. 1939 May 31;69(6):767–784. doi: 10.1084/jem.69.6.767. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Landsteiner K., Chase M. W. STUDIES ON THE SENSITIZATION OF ANIMALS WITH SIMPLE CHEMICAL COMPOUNDS : VII. SKIN SENSITIZATION BY INTRAPERITONEAL INJECTIONS. J Exp Med. 1940 Jan 31;71(2):237–245. doi: 10.1084/jem.71.2.237. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Landsteiner K., Jacobs J. STUDIES ON THE SENSITIZATION OF ANIMALS WITH SIMPLE CHEMICAL COMPOUNDS. II. J Exp Med. 1936 Sep 30;64(4):625–639. doi: 10.1084/jem.64.4.625. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lowney E. D. Immunologic unresponsiveness appearing after topical application of contact sensitizers to the guinea pig. J Immunol. 1965 Sep;95(3):397–403. [PubMed] [Google Scholar]
- MITCHISON N. A. INDUCTION OF IMMUNOLOGICAL PARALYSIS IN TWO ZONES OF DOSAGE. Proc R Soc Lond B Biol Sci. 1964 Dec 15;161:275–292. doi: 10.1098/rspb.1964.0093. [DOI] [PubMed] [Google Scholar]
- OORT J., TURK J. L. A HISTOLOGICAL AND AUTORADIOGRAPHIC STUDY OF LYMPH NODES DURING THE DEVELOPMENT OF CONTACT SENSITIVITY IN THE GUINEA-PIG. Br J Exp Pathol. 1965 Apr;46:147–154. [PMC free article] [PubMed] [Google Scholar]
- Turk J. L. Lymphocyte response to antigens. A. Afferent side of sensitization arc. Response of lymphocytes to antigens. Transplantation. 1967 Jul;5(4 Suppl):952–961. doi: 10.1097/00007890-196707001-00025. [DOI] [PubMed] [Google Scholar]
