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The effectiveness of antigen aerosol-induced desensitization has been investigated in guinea-pigs actively sensitized with antigen, alone or incorporated in Freund's adjuvants. Rates of desensitization, and the ability of animals to regain anaphylactic hypersensitivity following intensive desensitization, have been considered in terms of relative rates of antibody production, levels of circulating antibody, and qualitative differences in the antibody produced. A protective component observed during desensitization in adjuvant-treated animals is considered to be a property both of high levels of circulating antibody and of the presence of certain non-specific factors which interfere with the sensitization process. [ABSTRACT FROM AUTHOR]

Passive cutaneous anaphylaxis (PCA) was studied in guinea-pigs sensitized with rabbit antisera to bovine serum albumin or horse spleen ferritin and challenged 4-5 hours later with antigen. Ultrastructural studies of lesions obtained after sensitization or challenge indicated that substantial numbers of neutrophils had infiltrated into the skin. Following challenge these elements exhibited phagocytic activity, presumably representing the uptake of immune precipitates formed in the interstitial spaces. This was associated with degranulative and degenerative phenomena, suggesting that lysosomes were discharged extracellularly. A significant suppression of the intensity of the hyperpermeability response in PCA was noted when animals were pretreated with an antiserum to guinea-pig neutrophils. Antihistamines also suppressed PCA, and the combined effect of neutrophil depletion and antihistamine therapy was additive. It was concluded that a combination of anaphylactic (histamine release) and Arthus-like (neutrophil lysosome release) mechanisms mediated the vascular response in this type of PCA. [ABSTRACT FROM AUTHOR]

The oxygen consumption of isolated rat mast cells has been determined using a micro capillary, respirometer designed by Cunningham and Kirk and modified to permit stirring and addition of reactants. Uptake ranged from 0·5 pl. per cell per minute in 100 per cent O2 to 0·1 pl. per cell per minute in 1 per cent O2. It remained steady for at least 1 hour and was not affected by the presence of glucose. Under a variety of conditions neither histamine release by antigen added to sensitized cells nor by compound 48/80 added to normal cells resulted in any increase in the rate of oxygen uptake. Oxygen does not appear to be a rate limiting factor. [ABSTRACT FROM AUTHOR]

Some assumptions underlying the attribution of a high discriminatory capacity to anaphylactic tests have been investigated in model systems, using two tests of the anaphylactic response—the Dale-Schultze reaction and the measurement of histamine released from chopped lung. It has been demonstrated that there may be no response to challenge with a second antigen after desensitization to the first even though the tissues can be shown to be sensitized to the second antigen, i.e. there is a possibility of the occurrence of ‘false’ negative results. The potentiality of response to the second antigen appears to depend partly on the proportion it formed of the sensitizing mixture and partly on the absolute dose used in sensitization. It has been confirmed that desensitization is a graded phenomenon related to dose of antigen and it is shown that it is reversible with time. These factors are likely to complicate the performance and/or interpretation of experiments with tissue extracts and constitute a source of potential false positive results. These factors are of less importance with the histamine-release test than with the Dale-Schultz test. For the Dale-Schultz reaction the ileum proved to be a more satisfactory test tissue than the uterus. In general, there was no significant difference in discriminatory capacity between the histamine-release test and the Dale-Schultz test, but there were more sources of error in the performance of the Dale-Schultz test, while the histamine-release test though more laborious to do gave results which were more amenable to statistical analysis. It is concluded that with careful experimental design the tests could possibly be of use in some investigations of antigen mixtures provided that the sources of false positive results were recognized and due precautions taken. [ABSTRACT FROM AUTHOR]

A rapidly eliminated vital dye, available under the names Coomassie blue (CB) and fast Cyanine (FC), has been found suitable for the demonstration of local anaphylactic reactions in mice and guinea-pigs. Like other dyes used for this purpose, circulating CB/FC does not readily escape through the blood vessel walls except at sites of increased capillary permeability, as in local anaphylaxis. The blue-mauve colour obtained with CB/FC is almost as vivid as that given by Pontamine Sky Blue, and is as sensitive an indicator of both cutaneous and pinnal anaphylaxis. CB/FC can be given both intravenously and intraperitoneally for the demonstration of local anaphylaxis, and disappears from the animal, both locally and systemically, within 3-6 hours. Animals cleared of CB/FC can be re-dyed and re-challenged repeatedly. Other factors being equal, response at newly reactive sites are as good as those obtained originally at the initially reacted sites. Use has been made of the non-persistence of CB/FC in three situations requiring repeated challenge of the same animal: the development of pinnal anaphylactic sensitivity following antigen injection in mice; the effect of challenge by one antigen on the anaphylactic reactivity of a dually passively sensitized skin site on subsequent challenge with the same, or the other, antigen; and the effect of single antigen challenge on the pinnal anaphylactic reactivity of the ears of dually actively sensitized animals on subsequent challenge with the second antigen. In these investigation CB/FC has made it possible to challenge a single animal repeatedly, without interference of residual dye colour from previous challenges. This should make possible a more direct approach to problems in anaphylaxis which are best studied by repeated local reaction visualized by dye. [ABSTRACT FROM AUTHOR]

Rabbits injected with a pre-incubated mixture of benzyl penicillin and normal rabbit serum in Freund's complete adjuvant produced an antibody which reacted by tube precipitation, agar-gel diffusion precipitation, and passive cutaneous anaphylaxis with (1) a conjugate formed between benzyl penicillenic acid and human y globulin, and (2) one of four preparations of a mixture of benzyl penicillin and human γ globulin. Evidence was obtained that the penicillinprotein preparation was effective by virtue of penicillenic acid-protein groups that it contained. The theory that systemic penicillin sensitivity is due to allergy to conjugates formed in vivo between the benzyl penicillin derivative, benzyl penicillenic acid and plasma protein is reviewed. It is suggested that the experimental results obtained support this theory. [ABSTRACT FROM AUTHOR]

Passive cutaneous anaphylaxis in the guinea pig has been studied with rabbit antibody to a series of antigens of differing molecular weight. The results indicated that at a given antibody level the weight of antigen needed to elicit a reaction increases with its molecular weight. Previous observations have been confirmed that the amount of antigen needed to elicit a reaction at a high level of antibody is less than that required at a lower level. The results suggest that extremely small amounts of small molecular weight antigens might be sufficient to produce anaphylactic symptoms in highly sensitive individuals. [ABSTRACT FROM AUTHOR]

Mast cell damage, characterized by loss of granules, occurs when the tissues of sensitized guinea pigs are brought into contact with antigen in vivo or in vitro. Quantitative studies on the mesenteries of passively sensitized guinea pigs show that the mast cell response to antigen is well correlated with the development of anaphylactic shock. After multiple sensitization contact with different antigens caused cumulative, but not complete, disappearance of mast cells. Antigen-antibody interactions, in which antisera were from species which do not sensitize guinea pigs passively for anaphylaxis, did not cause mast cell damage. Reversed passive anaphylaxis and mast cell damage were elicited when the antigen was a suitable γ-globulin, but not an albumin. Antiserum against homologous γ-globulin causes typical anaphylaxis and mast cell degranulation, whereas antiserum against Forssman antigen causes capillary damage without mast cell changes, and antiserum against homologous albumin is ineffective. These findings can be explained by the hypothesis that mast cell damage occurs as a result of antigen-antibody interaction, when one of the reagents is reversibly adsorbed at the mast cell surface, and when they are together capable of activating some process or agent whose further action depends upon the metabolic integrity of the cells. [ABSTRACT FROM AUTHOR]

Using the criteria of generalized anaphylaxis, the Schuhz­Dale test, and mast cell degranulation occurring on contact with antigen in vitro, a study has been made of the ability of antisera, prepared in various species, to sensitize guinea pig tissues passively. Whereas small amounts of guinea pig and rabbit antibodies and rather larger amounts of monkey, dog and human antibodies were effective, antibodies from goat, horse, rat, fowl and a human auto-immune thyroid antiserum were ineffective. These results are in general agreement with those in the literature. Using antibodies labelled with 131I, no gross differences were found between those which sensitized and those which did not, either in respect of uptake on guinea pig mesentery in vitro, or retention in the tissue after uptake in vivo. By means of antigen labelled with 131I it was also shown that the antibody adsorbed on guinea pig mesentery could combine equally well with antigen, whether the antibody came from rabbit (sensitizing) or rat (non-sensitizing). These experiments also indicated that the amount of adsorbed antibody necessary for sensitization is very small. Reversed passive anaphylaxis was studied with a variety of different antigen-antibody systems, using the criteria listed above. It occurred when, but only when, the antigen was a γ-globulin, and when both antigen and antibody globulins came from species whose antibodies were able to sensitize guinea pigs for direct passive anaphylaxis. It is concluded that the explanation of the differences between antibodies or antigens which sensitize guinea pigs passively, and those which do not, is to be found in the nature of the antigen-antibody combination as well as in the manner of ‘fixation’ on the tissues. The possible importance of ability to activate guinea pig complement is discussed. [ABSTRACT FROM AUTHOR]

The capacity of denatured proteins to provoke anaphylactic sensitivity and delayed sensitivity in guinea pigs has been investigated. It has been found that heat-denatured proteins are as effective as native proteins in provoking delayed hypersensitivity to either material, in spite of the fact that such denaturation greatly modifies their antigenicity from the point of view of antibody production. Pure delayed hypersensitivity, moreover, occurs regularly in response to extremely minute amounts of a good antigen, whether native or denatured. It is further shown that immunological cross-reactivity can be demonstrated regularly by means of the delayed hypersensitivity reaction in guinea pigs, at a time when no cross-reacting antibodies of conventional type can be found. The significance of these observations in regard to the relationship between delayed hypersensitivity and antibody production is discussed. [ABSTRACT FROM AUTHOR]

Gel-filtration on Sephadex, of Ascaris, Nippostrongylus, Toxocara and Toxascaris antigens revealed that the allergenic components had a molecular weight range of 10,000–50,000. Allergenicity was assessed by homologous passive cutaneous anaphylaxis, to detect reagins in man and reagin-like antibodies in the rat and rabbit. It is suggested that nematodes can provoke a Type I allergic reaction in man, rat and the rabbit. [ABSTRACT FROM AUTHOR]

Presents a subject index of publications and related resources on immunology. Action of soluble antigen-antibody complexes in perfused guinea-pig lung; Applicability of anaphylactic tests in studies of antigen mixtures; Immunological responses of mammalian host against tapeworm infections.

Using bovine plasma albumin as an antigen anaphylactic sensitivity was found to be highly heritable, h²=0·92 (0·54 to 1·0). [ABSTRACT FROM AUTHOR]