Hypersensitivity Reactions In Guinea Pigs Research Articles

IgE antibody-mediated cutaneous basophil hypersensitivity reactions in guinea pigs.

Cutaneous basophil hypersensitivity (CBH) reactions are a heterogeneous group of delayed time course basophil-rich immune responses that can be mediated in the guinea pig by T cells, B cells, or IgG1 antibody. This study examined whether guinea pig IgE antibody could also mediate CBH reactions. IgE antibody to picryl or oxazolone determinants was induced by immunizing Hartley strain guinea pigs pretreated with cyclophosphamide. Hyperimmune serum from these animals was passed through a heavy chain-specific anti-IgG1 affinity column. The presence of IgE anti-hapten antibody in the filtrate fraction was verified by passive cutaneous anaphylaxis (PCA) testing with a 7-day period of local passive sensitization and by the heat lability (56 degrees C, 4 hr) of PCA activity. This IgE-rich fraction and the IgG1 fraction eluted from the column with base (0.2 M Na2CO3, pH 11.3) were transferred i.v. to separate groups of normal guinea pigs. Both fractions mediated delayed time course reactions that contained basophils. Macroscopic and microscopic reactions mediated by the IgE-rich fraction were abolished with heat (56 degrees C, 4 hr). Thus, two antigen-specific factors in guinea pig serum can mediate delayed time course basophil-containing reactions: IgG1 and IgE antibodies. IgE-mediated CBH reactions are similar to the late-phase reaction that follows IgE-dependent wheal-and-flare reactions in humans. The finding that guinea pig IgE can mediate a late reaction that contains basophils makes this a possible model for the human late-phase response, and suggests that some forms of CBH may play a role in human allergic disease.

D-penicillamine-induced enhancement of the delayed hypersensitivity reaction in guinea-pigs.

Intraperitoneal gelatin sponge implants were used in guinea-pigs to examine the effect of D-penicillamine on the delayed hypersensitivity reaction in vivo. When it was administered daily in a dose of 200 mg/kg for 14 days before sensitisation or for 14 or 30 days before challenge, D-penicillamine increased the number of exudate cells during the onset of the delayed hypersensitivity reaction. About 20% more polymorphonuclear cells accumulated in the sponges within 6-12 hours of implantation than did without D-penicillamine. Moreover, mononuclear cells also increased up to 20%, but this effect was apparent only 24 to 72 hours after sponge implantation and if D-penicillamine had been administered immediately before challenge.

Immediate hypersensitivity in the guinea pig conjunctiva. III. long-term persistence of the hypersensitive state and characterization of antibodies.

The ocular immediate hypersensitivity reaction in guinea pigs to topically applied normal rabbit serum can be evoked as long as 4 years after sensitization. The reaction was as severe and tended to persist for longer than that evoked 6 months after sensitization. Passive cutaneous anaphylaxis tests showed that very high titres of homocytotropic antibodies were present and that both IgE- and IgG1-like antibodies were involved. Sensitization with one set of injections instead of two was not consistently successful and the response on challenge was mild to moderate. Pretreatment of eyes with Isoptocarpine before antigenic challenge had no effect on the response. The addition of bacterial lipopolysaccharide to the first set of sensitizing injections produced hypersensitivity in animals which were otherwise refractory to sensitization.

Immunomodulating and antimetastatic activity of 3-(p-chlorophenyl) thiazolo[3,2-a]benzimidazole-2-acetic acid (Wy-18,251, NSC 310633).

The antimetastatic activity of a thiazolobenzimidazole, Wy-18,251 was investigated using various dosage regimens in mice with implanted Lewis lung tumors. The low doses, 1 and 5 mg/kg (i.p.) given 24 hours after implantation with two subsequent doses at 1 week intervals were most effective in reducing lung metastases. Delayed hypersensitivity reactions in guinea pigs were significantly increased by oral doses of 50 and 150 mg/kg. In normal rats, peripheral blood lymphocytes determined by rosette assay, were significantly increased by oral doses of 50 to 150 mg/kg of Wy-18,251 and in a more sensitive assay using anti-theta serum the lymphocyte levels were increased by doses of 7.5 and 10 mg/kg. When cultured T lymphocytes from CBA/J mouse spleens were incubated with a suboptimal concentration of Concanavalin A, [3H]thymidine uptake was significantly increased in the presence of 0.05 to 1.0 microgram per culture. These results suggest that Wy-18,251 may have potential therapeutic value as an antimetastatic agent through its stimulation of the cellular immune system.

Toxoplasma gondii: Immunopathology of cutaneous hypersensitivity reactions in guinea pigs injected with living parasites

Intradermal skin tests, consisting of viable Toxoplasma gondii organisms, were injected into normal guinea pigs and guinea pigs chronically infected with Toxoplasma. Subsequent gross and histological observations of the reaction sites were made. Whereas erythema and induration were present at the reaction site in normal animals, these criteria of delayed hypersensitivity (DH) were markedly increased in Toxoplasma-infected guinea pigs. Histologically, rapid mononuclear cell infiltration occurred early in the development of DH in immune animals, suggesting the appearance of a classical tuberculin DH reaction. The presence of numerous intracellular Toxoplasma organisms in the reaction sites of normal guinea pigs contrasted sharply with the inability to demonstrate any parasites at the site of infection in Toxoplasma-immune animals.

Pyrethrum dermatitis I. The allergenic properties of various extracts of pyrethrum flowers

AbstractExtracts of pyrethrum flowers were obtained by treatment with various aqueous and organic solvents. These were tested for immediate and delayed hypersensitivity reactions in guinea pigs previously sensitised to pyrethrum by single subcutaneous injection of the ground flowers suspended in Freund's complete adjuvant. Strong reactions were elicited by various aqueous extracts of the flowers; the allergens are of high molecular weight, being non‐dialysable. A hexane extract (similar to pyrethrum oleoresin) produced a moderate reaction, but a commercially refined pyrethrum extract proved negative.An extract of the spent flowers with methylene chloride showed irritant effects in unsensitised guinea pigs.

Hapten-Carrier Relationships in the Production of Rat Homocytotropic Antibodies

Abstract Various hapten-protein conjugates have been used to elicit the production of antibodies involved in immediate-type hypersensitivity reactions in immediate-type hypersensitivity reactions in guinea pigs (1, 2), mice (3), rats (4, 5) and man (6). In the guinea pig, the concentration, the relative proportions of γ1 and γ2 and the average intrinsic association constant of anti-2,4-dinitrophenyl (DNP) antibodies were shown to depend on the nature of the carrier molecule used for immunization (7). Soluble extracts derived from Ascaris suum injected in association with B. pertussis vaccine elicited high titers of homocytotropic (Hc) antibodies in the rat; compared with hemocyanin and ovalbumin, 10 times less Ascaris antigen was required to induce detectable levels of Hc antibodies (8). The present report deals with the production of rat Hc antibodies to three different dinitrophenyl-carrier conjugates. The results will show that both anti-DNP and anti-carrier antibody titers obtained in rats immunized with a DNP-Ascaris conjugate were significantly higher than those obtained against DNP-hemocyanin or against DNP-bovine gamma globulin.

The lungs as the site of delayed-type hypersensitivity reactions in guinea pigs

Guinea pigs immunized by a single intramuscular injection of dry killed tubercle bacilli were exposed to purified protein derivative (PPD). Respiratory frequency and airway resistance showed no obvious changes immediately after inhalation of PPD, but respiratory frequency increased gradually after 6 hours and reached a maximum around 24 to 48 hours. At this time respiratory frequency was 1.5 to 2.5 times more than the control and declined to the control values over the next 48 to 72 hours. The lungs showed gradually increasing hepatization-like changes which reached a maximum around 24 to 48 hours and gradually subsided within 7 days after inhalation of PPD. Histologically, polymorphonuclear cells were predominant initially but mononuclear cells became dominant in 24 to 48 hours. Considerable thickening of the interalveolar septa was observed. Guinea pigs passively sensitized with splenic cells showed identical changes although less marked.

The Effect of Ellagic Acid on Delayed Hypersensitivity Reactions in Guinea Pigs

Abstract Ellagic acid suppresses the cutaneous reactivity of guinea pigs with active delayed hypersensitivity. The intensity of Arthus reactions is reduced, and both heterologous passive cutaneous anaphylaxis reactions and the vascular component of delayed hypersensitivity lesions are significantly depressed.

Some immunological studies with heat-denatured bovine serum albumin and its peptic, tryptic, and chymotryptic peptides.

SummaryThe effect on passive anaphylaxis and delayed hypersensitivity in guinea pigs and immune tolerance in rabbits of injections of heat-denatured bovine serum albumin (HDBSA) and its dialyzable and non-dialyzable peptides, formed by the action of crystalline trypsin, chymotrypsin, and pepsin has been presented. In some experiments, a comparison has been presented with the effect of native bovine serum albumin (BSA). A direct relationship was observed between the molecular size of the peptides and their in vivo immunological activities. There were also some differences in the immunological activity of peptides formed by the different enzymes. Chymotryptic peptides were most effective in eliciting passive anaphylaxis; whereas, there were no significant differences in the ability of nondialyzable products of various enzymes in causing Arthus and delayed hypersensitivity reactions in guinea pigs. Heat denaturation did not affect the ability of BSA to cause Arthus and delayed reactions. In fact, HDBSA and B...

Hypersensitivity reactions in guinea pigs to group A hemolytic streptococci.

Hypersensitivity reactions in guinea pigs to group A hemolytic streptococci.

Desensitization to Delayed Hypersensitivity Reactions

Summary Delayed hypersensitivity reactions in guinea pigs sensitized to α,DNP(Lys)7–10 peptides could be specifically inhibited by prior intraperitoneal injection of the homologous immunizing antigen or by larger immunogenic α,DNP-oligo-L-lysyl peptides. Desensitization was short-lived and normal skin reactivity returned by 6 days. Small closely related nonimmunogenic α,DNP-oligo-L-lysines, oligo-L-lysines, or dinitrophenylated proteins were unable to desensitize these animals. The exquisite immunologic specificity and the requirement for an immunogenic molecule to desensitize as well as elicit the delayed response provides strong evidence for the concept that the initial event in the delayed response is an active process triggered by antigen rather than the result of passive interaction of preformed “delayed antibody” with antigen.

Immunochemical Studies on Delayed and Arthus-Type Hypersensitivity Reactions

Summary Studies of the immunochemical relationships between delayed and Arthus-type hypersensitivity reactions in guinea pigs sensitized to α, DNP, oligo-l-lysyl peptides have led to several observations. 1) Small nonimmunogenic members of the homologous series of peptides elicit only Arthus-type reactions. 2) Larger members which are immunogenic provoke both Arthus and delayed reactions. 3) Serum antibodies from these animals have permitted studies of quantitative inhibition of precipitation; the peptides show increasing efficiency of inhibition, on a molar basis, with increasing chain length, up to the heptamer. 4) The upper limit of combining-site size in this system appears complementary to the heptamer. 5) The maximum combining-site size corresponds in size to the smallest peptide in this series which is immunogenic. 6) Although the hexamer contributes approximately 96% of the binding energy of the heptamer with conventional antibody, the heptamer, but not the hexamer, elicits a delayed reaction. These results suggest that circulating high affinity antibody or antibody with a larger combining site is not the mediator of the delayed response. Since only immunogenic peptides provoke the delayed skin reaction in this system, the delayed response may depend on local biosynthesis of sufficient antibody (cell-bound or free) by sensitized lymphocytes to form antigen-antibody complexes capable of producing tissue damage. Under these circumstances, the need for a larger determinant to elicit the delayed response reflects on the immunogenicity of the material and not its complementariness to a combining site size on a preformed antibody molecule.

Studies on the Specificity of the Cellular Infiltrate of Delayed Hypersensitivity Reactions

Summary An autoradiographic study has been performed in an attempt to demonstrate specifically sensitized cells in delayed hypersensitivity reactions in guinea pigs. In one experiment, guinea pigs were given H3-thymidine at various times after immunization with a single antigen and all were skin tested 22 days after immunization. It was found that there was a continuous increase in the percentage of labeled mononuclear cells in skin reactions as a function of time of administration of H3-thymidine. In another experiment, guinea pigs were immunized with two unrelated antigens and given H3-thymidine in such a manner as to label cells proliferating in response to the first, but not the second antigen. No difference was detected in the percentage of labeled infiltrating mononuclear cells at skin reactions elicited simultaneously with each antigen at separate sites. These observations demonstrate that the specifically sensitized cells which are believed to initiate the inflammation of delayed hypersensitivity reactions are too few to be detected by the methods available.