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Intravenous injection of bovine serum albumin (BSA) into the BSA/CFA-primed ICR mice specifically induced anaphylactic death within 1 h. The anaphylactic death could not be induced until day 8 after sensitization, and sensitization subsisted for more than 3 months. The response was dose dependent; mice challenged with BSA doses higher or equivalent to 25 microgram developed anaphylactic death. The intravenous route was more effective than the intraperitoneal one, while subcutaneous injection was ineffective. Antigen in any of complete Freund's adjuvant, incomplete Freund's adjuvant or aluminum hydroxide could sensitize the mice to develop anaphylactic death. The combination of antigen and the mouse strain or the gender of the mouse determined the susceptibility of the anaphylactic death. AKR, B10.BR, as well as ICR, strains were susceptible. Antigen of HoGG induced a higher mortality rate than that of GAT or lysozyme. Male mice were more susceptible than female ones. The BSA-induced anaphylactic death could be prevented by pretreating ICR mice with cyproheptadine (histamine and serotonin antagonist) or diphenhydramine (histamine antagonist) and ketanserin (serotonin antagonist). Intravenous injection of saline during anaphylaxis also protected the mice from death. Furthermore, immune serum could transfer the anaphylactic death, and heat (56 degrees C, 4 h) did not destroy its activity. The primary IgG subclass induced by GAT, HoGG or lysozyme was IgG1. There was no qualitative difference in the IgG subclass induced in different strains by different antigens. The IgE class of antibodies was not detectable. These results suggest that there is a non-IgE-mediated anaphylactic death which involves the release of histamine and serotonin that cause the increase of vasopermeability and fatal blood volume loss.

Tachycardia and hypotension, two cardiovascular responses to anaphylaxis, were specifically induced by antigen in mice and rats, respectively. Intravenous injection of poly (Glu60Ala30Tyr10) (GAT) elicited tachycardia within 30-40 sec in GAT-primed B6 mice. Moreover, a minute amount of GAT (0.2 micrograms) was enough to sensitize the mice to subsequent GAT-induced tachycardia. Challenging doses ranging from 100 ng to 500 micrograms. could elicit tachycardia. The kinetics of tachycardia induction was different from that of antibody production or delayed-type hypersensitivity. Tachycardia was induced from day 6 after immunization, while delayed-type hypersensitivity developed as early as day 4, and anti-GAT antibodies were undetectable on day 6 and would not reach a maximum until day 8. Specific antigen-induced hypotension was also observed in rats. Furthermore, cardiovascular changes in both species could be passively transferred by heat-treated (56 degrees C, 30 min) sera from immunized animals. These benchmarks of antigen-induced cardiovascular changes in mice or rats could be used as models to study the immune control of cardiovascular changes in anaphylactic responses.

In addition to the delayed-type hypersensitivity (DTH), a unique type of hypersensitivity could be induced at a late stage of the immune responses after hepatitis B surface antigen (HBsAg) immunization. This antigen-specific ear swelling that develops within 1 h after antigen challenge has been referred to as the early-type hypersensitivity (ETH) in contrast to the 24-h DTH. Although expression of ETH was earlier than DTH, the induction of the former needed 3 days longer than that of the latter. In ETH, the plasma protein leaked into the tissue and the vasopermeability increased within 15 min, causing the oedema of ETH, The observation that cyproheptadine. not dexamethasone, inhibited ETH suggests that it is mediated through the release of histamine and/or serotonin, Furthermore, ETH could be transferred by immune sera. Heat treatment (56°C for 4 h) did not destroy the transfer, suggesting that it was not mediated by IgE. The human anti-HBs sera from either hepatitis B virus infection or HBsAg vaccinee also contained the activity to transfer the ETH in mice. [ABSTRACT FROM AUTHOR]

The surface envelope protein of hepatitis B virus (HBsAg) stimulates the immune system to produce anti-HBs antibodies and to generate cell-mediated immunity. These two arms of immunity were found to be regulated differently in bm12 (H-2bm12) or CBA and C3H (H-2k) mice. In bm12 mutant (1-Aβ mutant of B6 mice) mice, the anti-HBs production, early-type, and immune complex-type hypersensitivity were impaired, but the delayed-type hypersensitivity and the T-cell proliferation in vitro were normal compared to the parental B6 (H-2b) mice. The mutation of the Aβ molecule seems to affect the immune responses differentially. On the other hand, C3H or CBA mice produced antiHBs antibodies after major S protein (pre-S-depleted HBsAg) stimulation, but could not generate the hypersensitivity responses. The pre-S region could circumvent the non-responsiveness of the hypersensitivity response in C3H and CBA mice. These data suggest that the humoral and cellular immunities to the HBsAg particle are regulated distinctly and are affected by either the Afl molecule of the host or the pre-S region of the HBsAg. [ABSTRACT FROM AUTHOR]

Hepatitis B surface antigen (HBsAg) induced an immune complex-type hypersensitivity which developed at 5–6 hr after the challenge and could be transferred by anti-HBs antisera, in addition to the delayed-type hypersensitivity in B10.BR mice. The pre-S region of HBsAg influenced this induction because the pre-S-depleted HBsAg or recombinant major S protein could not stimulate this 5-hr car swelling. The male B10.BR mice responded batter than the female ones, probably due to the inhibition by female hormone. Furthermore, HBsAg could also induce an early-occurring hypersensitivity which appeared within 1 hr of the antigen challenge. However, B10.BR mice did not exhibit this hypersensitivity; B6 mice expressed all three types of hypersensitivity (1 hr, 5 hr and 24 hr) and BALB/c farce showed only 1-hr and 24-hr responses. The expression of the immune complex- type seems to be determined by the Ighb gene or gene(s) closely associated to it. Mice hearing the Igh-1b allotype could be stimulated by HBsAg to induce the immune-complex type hypersensitivity. Moreover, it was the high specific binding not the titre of anti-HBs antibodies that influenced the exhibition of immune complex-type hypersensitivity. [ABSTRACT FROM AUTHOR]

This report describes the alteration of helper-suppressor balances in an immune response (Ir) gene-controlled system by varying the route and form of antigen injection. Adult responder BALB/c mice develop Lyt 1+2-, T cells for delayed-type hypersensitivity (DTH), and T-cell proliferative (Tprlf) responses to subcutaneous injection of either poly(Glu60Ala30Tyr10) (GAT)-coupled syngeneic spleen cells (GAT-SP) or GAT emulsified in complete Freund's adjuvant. In contrast, intravenous injection of adult responders with GAT-SP results in specific unresponsiveness for DTH, Tprlf, interleukin-2, and plaque-forming cell (PFC) responses. This tolerance is mediated by both suppressor T cells (Ts) and a functional clonal inhibition. Lyt 1-2+ Ts suppress the induction (afferent limb) of GAT-specific DTH and PFC but not Tprlf responses. The reduced T-cell proliferation observed in GAT-tolerant mice is due to a non-transferable mechanism(s), possibly functional clonal inhibition. Our data are compatible with a multi-step pathway involving both proliferating and non-proliferating helper T (Th) cells. In addition, the fine specificity of tolerance induction for DTH and Tprlf responses was examined lay using the related antigens poly(Glu60Ala40) (GA) and poly(Glu50Tyr50) (GT). Tolerance is exquisitely specific, as GA tolerizes responses to GA and GAT, whereas GT tolerizes GAT but not GA responses. Thus, both the route and form of antigen administration are important to the induction and regulation of immune response in Ir gene-controlled systems. Possible mechanisms governing the Th/Ts balance and the induction of GAT-specific tolerance and suppression for cellular and humoral responses in adult responders are discussed. [ABSTRACT FROM AUTHOR]