Peter Abramoff

Immunologically induced lung disease in guinea pigs: A comparison of ovalbumin and pigeon serum as antigens☆☆☆★

This study was conducted to compare the capacity of pigeon serum (PS), an antigen (Ag) associated with hypersensitivity pneumonitis (HP), and ovalbumin (OA) in the induction of immunologic lung disease in guinea pigs (gp). Whereas OA was very effective in inducing a severe pneumonitis, PS failed to produce significant disease. A determination of the antibody (Ab) responses in OA- or PS-sensitized GP revealed that total Ab activity, as well as specific IgG1, and IgG2 responses, were not significantly different in the two groups. There was, however, a markedly higher IgE-like Ab response to OA than to PS. Thus, there was a striking correlation between specific IgE synthesis and the production of immunologic lung disease. The disease resembled immune complex disease histologically, and we suggest that the IgE antibody may function as a preceding anaphylactic trigger mechanism for the lodging of complement-fixing Ag-Ab complexes in the vasculature of the lung. It is further suggested that PS may be a poor Ag for the induction of IgE synthesis in guinea pigs.

Immune-complex disease in guinea pig lungs: I. Elicitation by aerosol challenge, suppression with cobra venom factor, and passive transfer with serum☆

Abstract Immune-complex disease was elicited in the lungs of ovalbumin-sensitized guinea pigs following an aerosol challenge with specific antigen. An acute inflammatory reaction, characterized by peribronchial polymorphonuclear leukocyte infiltration, edema, and hemorrhage, was observed 2 hr following aerosol challenge. This focal reaction developed into a diffuse reaction within 6 to 12 hr postchallenge. By 24 hr postchallenge, the acute inflammatory process had begun to resolve. The active disease was suppressed with cobra venom factor and was transferred to normal guinea pigs with immune serum.

ANTIBODIES TO SYNTHETIC HUMAN GASTRIN I

Abstract Antibodies to pure synthetic human gastrin I have been produced in chickens after injections of synthetic human gastrin I attached to polyacrylate latex particles. The presence of antibodies has been demonstrated by the qualitative precipitin ring test, precipitation in the Ouchterlony agar-gel system, and bioassay.

The effect of immunization on the uptake of intratracheally administered antigen.

Abstract The purpose of this study in rabbits was to evaluate the effect of immunization on the uptake of intratracheally administered 125I-labeled ovalbumin (OA) into the circulation. Immunization reduced the amount of trichloroacetic acid-precipitible antigen entering the circulation: this suppression of antigen uptake did not appear to be due to increased systemic clearance of immune complexes. The reduction of antigen appearance in the blood could largely be accounted for by factors in serum, presumably antibodies, since the reaction was immunologically specific and was transferrable to normal recipients with immune serum. The rate of antigen uptake into the blood, expressed as an appearance velocity, was reduced approximately four-fold in immunized animals compared to normal animals. In addition to reducing the uptake of OA through the lung, immunization also appeared to cause greater catabolism of the antigen in the lung.

Assessment of chemokinetic behavior of inflammatory lung macrophages in a linear under-agarose assay

Migration of cells in response to a chemoattractant gradient is influenced by directed migration (chemotaxis) and stimulated random motility (chemokinesis). The present study quantitated the chemokinetic motility of normal and inflammatory lung macrophages by performing the linear under‐agarose assay in the presence of uniform concentrations of chemoattractant. Under these conditions, cell motility can be likened to a molecular diffusion process. Mathematical analyses which describe molecular diffusion were then applied, allowing the quantitation of the parameter, μ, the cellular equivalent to the molecular diffusivity constant. Determination of changes in μ as a function of chemoattractant concentration revealed that the chemokinetic motility of alveolar macrophages recovered during the early stages of acute pulmonary inflammation was greater than that of normal alveolar macrophages and macrophages recovered later in the inflammatory response. The correlation of differences in macrophage chemokinesis with macrophage maturation and the relevance of these differences to macrophage accumulation during inflammation are discussed.

Competition of Antigens as Influenced by Spacing of Heterologous Antigen Injections.

Summary 1) Antibody responses of chickens to single, simultaneous, and spaced injections of bovine serum albumin and human gamma globulin at a dosage level of 40 mg per kilo of body weight are described. 2) Under conditions of simultaneous injection of BSA and HGG antibody responses to both BSA and HGG approximate those of their respective controls. 3) Results of the experiment in which injection of HGG was withheld until 24 hours after that of BSA indicate that antibody response to BSA was significantly reduced. 4) Antibody responses to BSA and HGG in animals in which injection of HGG was delayed for 48 hours approximate the responses of their respective controls. 5) It appears that the character of the antibody response to simultaneous injections of BSA and HGG is regulated by the parameters of dosage level and timing of injections. The authors gratefully acknowledge the technical assistance of Miss Norma Johnson.

Pulmonary Immune Effector Cells: II. Antigen-Specific Blastogenic Responsiveness of Lymphocyte Populations during Pulmonary Immune Complex Disease in Guinea Pigs

A guinea pig pulmonary immune complex disease was used to evaluate local antigen (ovalbumin)-specific lymphoproliferative responses in lung tissue, bronchoalveolar spaces, and hilar lymph nodes (HLN) at various time intervals after challenge. The responses of lung tissue and bronchoalveolar lymphocytes appear to be mediated by T cells, whereas the response of HLN lymphocytes was mediated by B and/or T cells, depending on the stage of the disease. The blastogenic response of HLN lymphocytes to concanavalin A was much greater than that observed in lung tissue or bronchoalveolar lymphocyte preparations, even after the removal of adherent cells, suggesting a possible inherent difference between these cell populations in their response to mitogen. This study demonstrates that lung tissue, bronchoalveolar, and HLN lymphocytes are not only capable of responding blastogenically to specific antigen, but that this responsiveness varies throughout the course of the disease. The lymphoproliferative responses and concurrent changes in the proportion of pulmonary immune effector cells are discussed in relation to cellular immunoregulation during the in vivo progression of this pulmonary immune complex disease.

Pulmonary Immune Effector Cells in Guinea Pigs with Immune Complex Disease. I. Changes in T- and B-Lymphocyte Populations after Exposure to Antigen

Changes in immunologic effector cell populations in lung tissue, bronchoalveolar spaces, tracheobronchial lymph nodes, spleen, and peripheral blood were evaluated during the course of a pulmonary immune complex disease in guinea pigs. The number of macrophages, lymphocytes, and neutrophils present in each cell population were determined. T and B lymphocytes were identified by E and EAC rosette formation, respectively. An increase in the total number of lymphocytes in tracheobronchial lymph nodes and a greater proportion of B cells in these lymphocyte populations were observed at 12 and 24 hr postchallenge. The total number of macrophages, lymphocytes, and neutrophils recovered from the bronchoalveolar spaces also increased, as did the proportion of lymphocytes and neutrophils. A similar proportional increase of lymphocytes obtained from lung tissue also occurred. The proportion of B cells in the lymphocyte populations of the bronchoalveolar spaces and lung tissue increased to a maximum at 24-48 hr postchallenge. Cell populations from peripheral blood or spleen remained stable, by all parameters examined, during the disease process. Thus, there appears to be a localization of the immune inflammatory response in the lungs during the course of this pulmonary immune complex disease. In addition, this study provides evidence that immune effector cells obtained by bronchial lavage accurately reflect the cellular changes associated with the acute inflammatory response in lung tissue and pulmonary lymph nodes.

Pigeon breeder's disease. Antibody response of man against a purified component of pigeon dropping extract.

Abstract A homogeneous component of pigeon dropping extract, one of the etiologic agents of pigeon breeders disease (PBD), was used to evaluate some of the antibody responses using serum from patients with PBD. Their responses were compared with those of similarly exposed, but asymptomatic, pigeon breeders. As assessed by antigen-binding capacity, quantitative precipitation, and complement fixation, the responses from these two groups were qualitatively similar. In general, these results are in agreement with other studies using pigeon serum components. Since symptomatic and asymptomatic pigeon breeders are not readily discriminated by results of tests for humoral immunity, we suggest that other factors are important in the pathogenesis of PBD.

Specificity of Anamnestic Response in Chickens.

Summary 1) The effects of secondary injections of various soluble protein antigens, subsequent to disappearance from the circulating system of antibodies to a primary antigen, are described. 2) Secondary antigen injections do not elicit antibody responses to previously injected antigens, if the antigens are unrelated. 3) Quantitative levels of antibody response to secondary antigens are apparently unaffected by previous antigenic stimulations of the animal, if the antigens are unrelated.