Sheldon G. Cohen

Cutaneous sensitization to blue-green algae

Abstract 1.1. A case history is presented in which a child developed an erythematous-papulo-vesicular dermatitis of the exposed portions of the body on swimming in a lake containing a water bloom of blue-green algae. 2.2. The patient was found to have an allergic contact type dermatitis due to cutaneous sensitivity to phycocyanin, the blue pigment found in Anabena.

Experimental eosinophilia: VIII. Cellular responses to altered globulins within cutaneous tissue

Inflammatory cell responses to cosinotactic agents were studied in the guinca pig under short-term experimental conditions designed: (1) to cxclude possible associated antibody formation, and (2) to produce preliminary histaminic influences on challengcd tissue sites. Localized eosinophil cell infiltrations into dermis developed six hours after intracutaneous challenge to: (1) molecular aggregates of rabbit serum gamma globulins, (2) preformed soluble antigen-antibody complexes prepared in vitro from bovinc gamma globulin (BGG) and corresponding rabbit antiserum, and (3) BGG antigen-antibody systems through passive sensitization techniques. Exogenous histamine neither evoked an cosinophilia per se nor exerted synergistic or potentiating influences on specifically challenged dermal sites. Pre-existing states of immediate hypersensitivity to unrelated antigen (i.e., ovalbumin or hemocyanin) did not affect eosinophil leukocytc responses to gamma globulin aggregates. The prompt emergence of eosinophil cell-containing infiltrates within tissue devoid of demonstrated antibody forming elements suggests that the eosinotactic influences may have been related to the gamma globulin complexcs. This in turn may be a function of their state of molecular aggregation.

Experimental eosinophilia IV. Eosinotactic influences of polysaccharides

Abstract The administration of heterologous and homologous species glycogen, soluble starch amylodextrin, starch amylopectin, laminarin, inulin, or high molecular weight dextran into the rabbit foot pad resulted in 4-hour eosinophilic granular cell infiltrations into the sinuses of regional popliteal lymph nodes. Similar histologic alterations could not be demonstrated with component monosaccharides or with other non-carbohydrate macromolecular histamine-releasing agents including acacia, stilbamadine, peptone, trypsin, polyvinylpyrrolidone, or polymyxin B. The eosinotactic effects of glycogen were studied through the use of chemical inhibitors and antagonists. These effects could not be related to release of histamine, serotonin, or heparin. Precipitation of amylodextrin and amylopectin by normal sera suggests the possibility of participation of some polysaccharides in immune reactions with preformed antibody. However, the eosinotactic effects of polysaccharides could not be related to any delineated immunologic phenomena or chemotactic action.

Variations in egg white and egg yolk components of virus and rickettsial vaccines.

Abstract 1.1. Rabbit antisera to chicken egg white and to egg yolk demonstrated common antibody constituents by double diffusion precipitin studies in agar gel with the Ouchterlony technique. Because of impurities in the egg white fractions, the antigen common to egg white and egg yolk could not be definitely identified as ovalbumin and/or conalbumin. 2.2. These antisera were employed in similar precipitin test procedures to detect qualitative egg white and egg yolk components of some virus and rickettsial vaccines of chick and duck embryo origin. 3.3. A wide variation in the number and types of component egg white and egg yolk fractions was found to exist among the vaccines. 4.4. It is suggested that one determinant of allergic reactivity for a vaccine requiring chick embryo culture in its preparation might be the variable presence of that particular protein fraction of egg white and/or yolk for which the recipient may possess clinical sensitivity.

Experimental eosinophilia X. Relation of antigen-antibody complex size and protein molecular weight to cell responses.

Summary Eosinophil infiltrations were found in guinea pig popliteal lymph nodes 6 hours after foot pad injections of purified proteins or corresponding soluble antigen-antibody complexes. Quantitated cell responses in this model served to evaluate eosinotactic influences of primary antigen exposure and of antigen-antibody union. Ribonuclease (BRN), serum albumin (BSA), gamma globulin (BGG), and thyroglobulin (BTG) of bovine origin; horse spleen ferritin (HSF), hemo-cyanin (HCN) from Homarus americanus, and tobacco mosaic virus (TMV) were used as representative purified proteins ranging in molecular weights from 13,000 to 40,700,000 and to prepare a spectrum of soluble complexes with rabbit antibody in moderate excesses of antigen. In equal weight dosages the smaller complexes and preparations of lower molecular weight proteins evoked significantly greater eosinophilia (BRN > BSA, BGG, HSF>BTG, HCN, TMV). When dosages of the preparations from specific proteins (BRN, BSA, BGG, BTG, HCN) were based on equivalent numbers of moles, significant differences were not found. It is suggested that the number rather than size of presenting antigen-antibody complexes or protein molecular aggregates may be one critical factor in the degree of emerging eosinophilia of inflammatory cell responses.

Experimental eosinophilia: Studies on the origin and relationship of tissue eosinophil cells to peripheral blood eosinophilia

Abstract 1.1. A total of eighteen rabbits were given injections of erude beef liver extract by intramuscular, intraperitoneal, and intravenous routes in an attempt to induce an eosinophil cell response in peripheral blood, bone marrow, and splenic parenchyma. 2.2. Six of the animals received only crude beef liver extract for a six-week period. These developed a maximum rise in circulating blood eosinophils by the third week. 3.3. Six of the rabbits also received beef liver extract for a six-week period, but when a significant rise of circulating eosinophils had been reached by the third to fourth week, nitrogen mustard was administered intravenously and simultaneously with the liver extract during the remainder of the experimental period. The previously noted eosinophilia was then reversed to eosinopenic levels and was associated with leukopenia and lymphocytopenia. 4.4. Six of the animals received nitrogen mustard for two weeks prior to the injection of beef liver extract. This resulted in the development of peripheral blood cosinopenia and leukopenia. When cosinopenia had been established, the simultaneous administration of beef liver extract with nitrogen mustard failed to raise significantly the level of circulating eosinophils. 5.5. Crude beef liver extract adsorbed on aluminum hydroxide gel was injected intradermally into each animal at the start of the experiment, at the height of circulating cosinophilia, prior to the initial administration of nitrogen mustard, and at the conclusion of the course of parenteral beef liver extract injections. All locally injected skin sites were biopsied forty-eight hours following intradermal injections. 6.6. Infiltrations with eosinophilic granular cells were noted in the epidermis and corium of all animals, regardless of whether peripheral blood eosinophilia was present, had been reversed, or had been prevented from developing by the administration of nitrogen mustard. 7.7. Eosinophilic cellular infiltration into the splenic parenchyma was demonstrated microscopically in all rabbits to whom only beef liver extract was administered. In those who had also received nitrogen mustard, an absence of eosinophilic infiltration and the presence of atrophy of the lymphoid follicles were observed. 8.8. All animals treated with only beef liver extract exhibited marked hyperplastic granular eosinophilic bone marrows. Those who had been treated with nitrogen mustard prior to or simultaneously with liver extract exhibited agranular bone marrows with absence of eosinophilic precursor cells. 9.9. Precipitating antibodies to beef liver extract could not be demonstrated in the sera of all animals treated with this material. The development of cutaneous eosinophilic cellular infiltration could not be correlated with associated antibody response or antigen-antibody reaction. 10.10. Within the limitations of this experimental procedure, these results suggest that in the rabbit the development of a tissue eosinophilic cellular response may not be related to the presence of circulating peripheral blood eosinophils and local tissue eosinophils of the skin may have a source of origin independent of peripheral blood eosinophils. However, the exact origin or mode of their formation is not apparent.

The etiological role of streptococcus toxin-antitoxin systems in the experimental production of arterial sensitization

Abstract 1.1. Thirty rabbits were passively immunized with 1,500 U.S.P.H.S. units of streptococcus antitoxin (horse globulin) and beginning two to six hours later were given 15,000 S.T.D. streptococcus erythrogenic toxin in divided doses. 2.2. Twenty-four hours later these animals were sacrificed and sections taken for microscopic study. Microscopic pathologic lesions were found in fourteen of the rabbits and involved the small pulmonary arteries, pulmonary arterioles, and occasionally the pulmonary venules. The lesions consisted chiefly of a periarteriolar and a mild panarteriolar infiltration especially of eosinophils and to a lesser extent of lymphocytes, plasma cells, and neutrophils. 3.3. Five rabbits received a similar dose of streptococcus antitoxin alone, and five received the same dose of streptococcus toxin alone. Ten rabbits were passively immunized with streptococcus antitoxin and of these, five were challenged with diphtheria toxin and the remaining five with Veldee media. Five rabbits were passively immunized with tetanus antitoxin and five received normal horse serum prior to the administration of challenging doses of streptococcus erythrogenic toxin. In all thirty of these animals there were no pulmonary vascular lesions observed after twenty-four hours. 4.4. The lesions of pulmonary periarteritis and panarteritis in those rabbits passively immunized against and challenged with streptococcus erythrogenic toxin were less frequently and uniformly produced and were of a less severe degree of involvement than found in a series of rabbits that had been passively sensitized against and challenged with horse serum. 5.5. Apart from quantitative differences, qualitatively the lesions were histologically identical in rabbits subjected to passive sensitization and challenge, regardless of whether the antibody-antigen system employed was homologous antihorse serum-horse serum or heterologous species streptococcus antitoxin-erythrogenic toxin.

Reserpine effects and experimentally produced lesions of cardiovascular sensitization and eosinophilia

Abstract 1.1. A series of thirty rabbits were subjected to active sensitization and subanaphylactic challenge techniques with bovine serum favorable for the development of histologic lesions of glomerulitis, myocarditis, and pulmonary periarteritis and panarteritis. Fifteen of these animals were simultaneously treated with reserpine in an attempt to induce and maintain an associated state of serotonin tissue release and depletion. 2.2. The development of lesions of proliferative glomerulitis was found to be unaffected by reserpine treatment. 3.3. Evidence of myocarditis was found in all thirty animals, but it was considerably less extensive and of a milder degree in the reserpine-treated group. 4.4. All fifteen rabbits in the control sensitized and challenged group demonstrated lesions of pulmonary periarteritis and panarteritis. In five of the fifteen reserpine-treated animals evidence of vasculitis was absent and in the remaining four rabbits the lesions of pulmonary arteritis were of an equivocal nature, in contrast to those observed in the untreated group. 5.5. Crude beef-liver extract was administered to twelve rabbits in accordance with a technique designed to effect eosinophilia of the peripheral blood and bone marrow and eosinophilic granulocytic cellular infiltration into cutaneous tissue sites. Six of these animals were simultaneously subjected to the serotonin-releasing effects of reserpine. 6.6. Reserpine treatment failed to influence the development of peripheral blood or bone marrow eosinophilia or the histologic lesions of eosinophilic granular cell infiltrations into cutaneous sites.

Staphylococcus aureus antigens in hypersensitivity reactions and experimental arterial sensitization

Abstract 1.1. The sensitizing properties of Staphylococcus aureus (Wood 46 strain) were studied, utilizing soluble cell protoplasm obtained by exposing live bacterial cells to the disrupting effects of ultrasonic vibrations and pepsin-digested culture filtrate (toxoid) as antigens. 2.2. In rabbits passively sensitized with high-titer bacterial agglutinating antisera, fatal anaphylaxis could be uniformly elicited by subsequent intravenous challenge with a soluble preparation of bacterial cytoplasm. 3.3. When the previously determined critical anaphylactic dose of soluble bacterial cellular protoplasm was administered intravenously in fractional dosages over a sixty-minute time period to rabbits passively sensitized with the same high-titer bacterial agglutinating antiserum, lesions of pulmonary periarteritis and panarteritis were demonstrated twenty-four hours later. 4.4. Lesions of pulmonary panarteritis and periarteritis were also observed when similar techniques were employed in rabbits passively sensitized with high-titer bacterial agglutinating antiserum and challenged with toxoid and in rabbits passively sensitized with antitoxin and challenged with either toxoid or soluble bacterial cellular protoplasm. 5.5. Neither anaphylactoid reactions nor the development of lesions of pulmonary periarteritis or panarteritis were observed in normal rabbits receiving only the same bacterial agglutinating antisera, antitoxin, soluble bacterial protoplasm, or toxoid. 6.6. The intracutaneous injection of preparations of soluble bacterial cellular protoplasm in normal nonsensitized rabbits resulted in the development of cutaneous lesions of erythema, edema, infiltration, and necrosis. This resembled the dermonecrotizing action of Staphylococcus aureus toxin and may have been due to the antigenic exotoxin components previously demonstrated within Staphylococcus aureus bacterial cells. 7.7. The sensitizing properties of the cytoplasm and toxin of Staphylococcus aureus, their antigenic relationships, and their ability to participate in such in vivo reactions of hypersensitivity in the rabbit as anaphylaxis and the development of tissue manifestations of vascular sensitization have been demonstrated.

Phylogeny of hypersensitivity. I. anaphylactic responsiveness of the frog, Rana pipiens*

Rana pipiens immunized with Salmonella typhosa vaccine developed (anaphylactic) shock reactions on challenge with corresponding soluble bacterial antigen (SBA) but not with washed organisms. Hemagglutinating serum antibody to lipopolysaccharide (LPS) and anti-H agglutinins were demonstrated in responsive frogs. Shock reactions were not influenced by hibernation at 4° C. or by total aqueous immersion. Less uniform results were produced by challenging injections of bovine gamma globulin in 6 of 36 frogs that developed corresponding 2-mercaptoethanol (2-ME)-sensitive hemagglutinating antibodies and 2-ME-resistant precipitins following effective immunization with bovine gamma globulin (BGG) added to typhoid vaccine. Rabbit antiserum to S. typhosa containing anti-O and anti-H agglutinins, 2-ME-sensitive hemagglutinating antibody to LPS, and 2-ME-resistant precipitins to SBA passively transferred anaphylactic responsiveness to the frog, but this could not be effected with rabbit antiserum to BGG. Identification of a shock organ or pathologic changes could not be demonstrated in affected animals. The frog, an ectothermic amphibian representing a transitional position on the phylogenetic scale in production of specific immunoglobulin classes, may develop hypersensitivity manifestations under delineated conditions of exposure and challenge to a microbial antigen .