scholarly journals PHENOMENON OF LOCAL SKIN REACTIVITY TO BACTERIAL FILTRATES: PASSIVE IMMUNITY TO REACTING FACTORS

1931 ◽  
Vol 54 (1) ◽  
pp. 1-10 ◽  
Author(s):  
Gregory Shwartzman

It has proved possible to elicit passive immunity to B. typhosus reacting factors by means of normal and immune homologous neutralizing antibodies. The in vivo serum protection against these factors followed the law of multiple proportions. There was observed a considerable loss of antibodies from the blood stream. Passive immunity was best obtained when the immune serum was injected intravenously ½ hour before the intravenous injection of the reacting factors. It was possible to prevent the occurrence of the local skin reaction by an intravenous injection of serum after the intravenous injection of the reacting factors, provided the serum dose was very large and provided the serum injection was made immediately after the filtrate injection. A number of experiments clearly demonstrated the interesting fact that the greater the amount of antiserum injected intravenously, the more efficient was the in vivo neutralization, in a ratio distinctly greater than the quantitative increase of serum. It is suggested that there may be a practical value of the observation in relation to serum therapy. The results also demonstrated passive serum protection against the lethal effect of B. typhosus "agar washings" filtrates, in a ratio which seemed to suggest the law of multiple proportions.

1985 ◽  
Vol 31 (12) ◽  
pp. 1152-1156
Author(s):  
Thomas Fitzgerald

The in vitro effects of antibodies, complement, and (or) macrophages on Treponema pallidum have been previously characterized using relatively simple systems of organisms incubated with the immune components. In vivo, the more complex environment may alter immune reactivity. Experiments were performed to determine whether immobilizing and neutralizing antibodies retained their effectiveness in a more complex environment involving cultured mammalian cells. Two different protocols were used. In protocol A treponemes and normal or immune serum were mixed and added immediately to the cultured cells. In protocol B treponemes were preincubated for 18 h with cultured cells to maximize treponemal attachment; then normal or immune serum was added. With both protocols, attachment of organisms resulted in less effecient immobilization and neutralization. In further experiments, cultured cells were disrupted with Triton X, leaving cytoskeletal remnants on the vessel surface. Identical immobilization and neutralization experiments were performed in the presence of these remnants. In contrast to the findings with viable cultured cells, treponemal attachment to these nonviable remnants did not effect either antibody reaction. Attached organisms were immobilized or neutralized just as efficiently as unattached organisms. Results are discussed in terms of the altered immune reactivity in more complex in vitro environments.


1940 ◽  
Vol 71 (3) ◽  
pp. 409-423 ◽  
Author(s):  
Reginald D. Manwell ◽  
Frederick Goldstein

The effect of therapy with immune serum has been studied in thirty-two cases of Plasmodium circumflexum infection, all of them produced by blood inoculation. Eighteen of these cases never showed parasites, and seven others developed infections which were definitely milder than those of the controls. The therapeutic serum was in all cases obtained from chronic cases which had previously been superinfected to raise the immune titre. It seems justifiable to conclude that: 1. Passive immunity can be conferred in avian malaria, at least when caused by Plasmodium circumflexum just as it can be in certain types of monkey malaria, and perhaps in human malaria as well. 2. Whatever the nature of the protective substances present in the serum of chronic cases may be, they are present in very low concentration. Their concentration can be raised by superinfection, however. These substances may be strain-specific or species-specific, but the results of these experiments do not give any clear-cut answer to this question. 3. Serum therapy previous to infection seems to be more effective than when given afterward. 4. The administration of normal serum or even of physiological saline in a dosage comparable to that employed with the immune serum used in these experiments produced similar macroscopic changes in the size of the spleen. 5. Agglutination of cells parasitized by Plasmodium circumflexurn when mixed with immune serum was observed.


1929 ◽  
Vol 50 (4) ◽  
pp. 521-531 ◽  
Author(s):  
Walther F. Goebel ◽  
Oswald T. Avery

It has been demonstrated that many multiples of minimal doses of Bacillus typhosus reacting factors can be neutralized by specific immune sera. The potency of a given serum can be conveniently titrated against increasing amounts of reacting factors. If the immune serum is diluted or if the amount of the reacting factors is too large for a given amount of serum, there is obtained neutralization but only irregularly. Normal and heterologous sera (therapeutic meningococcus and erysipelas horse sera) free of normal agglutinins or possessing normal agglutinins of a low titer (1:16) for Bacillus typhosus are not able to neutralize the reacting factors. There is obtained questionable neutralization with a serum possessing normal Bacillus typhosus agglutinins in dilution 1:64. The titer of the neutralizing antibodies increases in the course of immunization. Immune sera exercise a definite protection against the mortality induced by intravenous injection of Bacillus typhosus culture filtrates.


2014 ◽  
Vol 61 (3) ◽  
Author(s):  
Barbara Kalenik ◽  
Róża Sawicka ◽  
Anna Góra-Sochacka ◽  
Agnieszka Sirko

Passive immunity is defined as a particular antigen resistance provided by external antibodies. It can be either naturally or artificially acquired. Natural passive immunization occurs during pregnancy and breast-feeding in mammals and during hatching in birds. Maternal antibodies are passed through the placenta and milk in mammals and through the egg yolk in birds. Artificial passive immunity is acquired by injection of either serum from immunized (or infected) individuals or antibody preparations. Many independent research groups worked on selection, verification and detailed characterization of polyclonal and monoclonal antibodies against the influenza virus. Numerous antibody preparations were tested in a variety of in vitro and in vivo experiments for their efficacy to neutralize the virus. Here, we describe types of antibodies tested in such experiments and their viral targets, review approaches resulting in identification of broadly neutralizing antibodies and discuss methods used to demonstrate their protective effects. Finally, we shortly discuss the phenomenon of maternal antibody transfer as a way of effective care for young individuals and as an interfering factor in early vaccination.


1950 ◽  
Vol 91 (1) ◽  
pp. 65-86 ◽  
Author(s):  
Duard L. Walker ◽  
Frank L. Horsfall

There is an exponential linear relationship between the quantity of influenza virus neutralized and the quantity of immune serum employed in in ovo neutralization. The slope of the neutralization line is extremely steep. The concentration of neutralizing antibody can be measured with considerable precision in ovo if the constant virus-varying serum technique is utilized. The amounts of hemagglutination-inhibiting and neutralizing antibodies which are absorbed by a given quantity of influenza virus (PR8) were found to be predictable and the degree of reactivity of these two antibodies was shown to be directly related to the extent of immunization. It was demonstrated that there are marked discrepancies in correlation between antibody titers obtained by in vitro hemagglutination-inhibition and in vivo neutralization techniques and that neutralizing antibody is preferentially absorbed by a given quantity of virus. Inasmuch as the results were found not to be attributable to peculiarities of the techniques employed, it appears that the antibodies measured by hemagglutination-inhibition in vitro and by neutralization in vivo are not identical.


1904 ◽  
Vol 4 (1) ◽  
pp. 31-72 ◽  
Author(s):  
E. F. Bashford

By means of the graphic records given on Plates II–VI and VIII the following facts have been illustrated.Immunity to Erythrocytes.Normal rabbit's serum is relatively innocuous for bullock's erythrocytes. The serum of an immunised rabbit acquires the power to dissolve bullock's erythrocytes.Besides acquiring the power to dissolve bullock's erythrocytes, an immune serum may also acquire power to clump them, and it has been shown that the phenomena of haemolysis and of agglutination are independent.The powers acquired by the immune serum can be artificially modified. The serum may be deprived of its powers by heat. Serum cautiously so deprived of its haemolytic power can have it restored by the addition of normal serum. The haemolytic power of the un-heated serum is augmented if normal serum be superadded.It has been shown that an immune serum only differs from a normal serum by its containing antitoxic bodies which are endowed with powers of specific reaction with the bullock's erythrocytes.The mechanism by which erythrocytes are laked by an immune serum has been analysed, and it has been shown that the solution of the erythrocytes is effected through the intervention of an anti-erythrocytic body called forth by immunisation. The erythrocytes which have been subjected to the action of this product of immunity give indication of their reaction with it if they are subsequently or concomitantly placed under the influence of normal serum. The erythrocytes and normal serum together, therefore, form a combined indicator of the presence of the anti-eiythrocytic body. The part played by normal serum has nothing to do with the acquisition of immunity.The only conclusion drawn from the above observations is that in the production of immunity to erythrocytes the serum of the immunised animal acquires certain powers which are concomitant with, but are not necessarily the cause of the immunity. This special case of immunity to erythrocytes is therefore probably parallel to induced immunity to those bacterial toxines for which antitoxines are known to exist.The course and progressive augmentation of artificial immunity to erythrocytes has also been illustrated, and it has been shown that erythrocytes saturated with anti-erythrocytic body retain the power to augment the immunity of an already immune animal.The serum of an animal actively immunised has power to confer passive immunity upon other animals, and the course of this passive immunity differs in the two cases when it is induced in the same species and in a species alien to that providing the immune serum.The experiments with bullock's erythrocytes have been repeated in parallel observations with ricin in order to permit of the observations on haemolysis being utilised in drawing conclusions on the behaviour of bacterial toxines.By adjusting the conditions of experiment in such a way that the minimal lethal dose for an animal was also the minimal agglutinating dose in test-tube experiments, it has been possible to give graphic records showing the parallelism between the processes when erythrocytes or living animals are used as indicators of the presence of free ricin. In this way it has been possible to illustrate the determination of the minimal lethal and minimal agglutinating doses of ricin and that quantity of antitoxine (antiricin) which is necessary to abolish the corresponding actions in the animal and in the test-tube, and to show that the mixture of toxine and antitoxine which is physiologically neutral in vitro is also physiologically neutral in vivo within the limitations imposed by the preliminary determinations.The consequences of conferring passive immunity upon the guinea-pig by means of active immune serum of the rabbit have also been illustrated, and it has been shown that the alien antiricin serum leads to the production of agencies directed against itself.Ricin neutralised by antiricin retains its power to produce immunity when injected into the species of animal which has yielded the antiricin.In connection with the conference of immunity to erythrocytes and to ricin, the nature of the difference between normal and immune sera has been studied. Attention has been directed to the possession by normal sera of properties which simulate those possessed in more marked degree by the immune sera. In the case of haemolysis, it has not been possible to clearly demonstrate that the actions manifested by the normal and immune sera are distinct, although the weight of evidence is in favour of this view. In the case of ricin, however, it has been possible to demonstrate that the immune serum possesses properties which are quite distinct from those possessed by normal serum, and that the latter does not interfere with the action of ricin because of the natural presence of a trace of antiricin. In the case of immunity to ricin, the antitoxine is certainly something which has been super-added to the serum in consequence of the process of immunisation.The facts ascertained in regard to artificial immunity to erythrocytes and to ricin completely agree. Only in oue point is it impossible to be quite sure that the phenomena are identical, viz., in the simulation by normal serum of the powers characteristic of the immune serum; for the demonstration that the two are distinct has been possible for ricin, but open to doubt in the case of erythrocytes. My investigations have been extended to diphtheria and tetanus toxines and to cobra venom, kindly placed at my disposal by Sir Thomas R. Fraser. They have however been interrupted, but so far as they go they support fully the observations made on ricin and erythrocytes.


2012 ◽  
Vol 19 (7) ◽  
pp. 1075-1082 ◽  
Author(s):  
Patricia M. Day ◽  
Yuk-Ying S. Pang ◽  
Rhonda C. Kines ◽  
Cynthia D. Thompson ◽  
Douglas R. Lowy ◽  
...  

ABSTRACTPapillomavirus L2-based vaccines have generally induced low-level or undetectable neutralizing antibodies in standardin vitroassays yet typically protect well againstin vivoexperimental challenge in animal models. Herein we document that mice vaccinated with an L2 vaccine comprising a fusion protein of the L2 amino acids 11 to 88 of human papillomavirus type 16 (HPV16), HPV18, HPV1, HPV5, and HPV6 were uniformly protected from cervicovaginal challenge with HPV16 pseudovirus, but neutralizing antibodies against HPV16, -31, -33, -45, or -58 were rarely detected in their sera using a standardin vitroneutralization assay. To address this discrepancy, we developed a neutralization assay based on anin vitroinfectivity mechanism that more closely mimics thein vivoinfectious process, specifically by spaciotemporally separating primary and secondary receptor engagement and correspondingly by altering the timing of exposure of the dominant L2 cross-neutralizing epitopes to the antibodies. With the new assay, titers in the 100 to 10,000 range were measured for most sera, whereas undetectable neutralizing activities were observed with the standard assay.In vitroneutralizing titers measured in the serum of mice after passive transfer of rabbit L2 immune serum correlated with protection from cervicovaginal challenge of the mice. This “L2-based”in vitroneutralization assay should prove useful in critically evaluating the immunogenicity of L2 vaccine candidates in preclinical studies and future clinical trials.


1929 ◽  
Vol 50 (4) ◽  
pp. 513-520 ◽  
Author(s):  
Gregory Shwartzman

It has been demonstrated that many multiples of minimal doses of Bacillus typhosus reacting factors can be neutralized by specific immune sera. The potency of a given serum can be conveniently titrated against increasing amounts of reacting factors. If the immune serum is diluted or if the amount of the reacting factors is too large for a given amount of serum, there is obtained neutralization but only irregularly. Normal and heterologous sera (therapeutic meningococcus and erysipelas horse sera) free of normal agglutinins or possessing normal agglutinins of a low titer (1:16) for Bacillus typhosus are not able to neutralize the reacting factors. There is obtained questionable neutralization with a serum possessing normal Bacillus typhosus agglutinins in dilution 1:64. The titer of the neutralizing antibodies increases in the course of immunization. Immune sera exercise a definite protection against the mortality induced by intravenous injection of Bacillus typhosus culture filtrates.


1932 ◽  
Vol 56 (5) ◽  
pp. 677-686 ◽  
Author(s):  
Gregory Shwartzman

In this paper there are reported observations on a certain new reactivating property of normal and immune blood sera of various animal species. The effect of the reactivating sera consists in restoration of the toxicity in vivo and in vitro of completely neutralized meningococcus and B. coli reacting factors. The property is apparently non-specific, heat-labile, lessens on storage, and has no relationship to complement. Heating of immune sera to a temperature destructive for the reactivating property but innocuous to the neutralizing antibodies, raises considerably their neutralizing potency. The possible immunological significance of the reactivating property is discussed in this paper.


1917 ◽  
Vol 26 (1) ◽  
pp. 119-138 ◽  
Author(s):  
Carroll G. Bull ◽  
Ida W. Pritchett

Five cultures of Bacillus welchii have been studied and compared Four came from infected wounds in the western theatre of war, and one was obtained from a personal article of clothing. Each culture possesses the essential characteristics ascribed to that group of bacteria. The infectious processes caused by the five cultures in rabbits, guinea pigs, and pigeons, are local in character; and very few or no bacilli enter or are found in the general blood stream during life or immediately after death. Glucose broth cultures, injected intravenously, are fatal to rabbits. Death occurs, almost immediately or after a few hours. Agglutinative bacterial emboli have been ruled out as the cause of death, as has been an acid intoxication. The fluid part of the culture acts in the same manner as the full culture and irrespective of neutralization with sodium hydroxide. The full cultures and supernatant fluid are hemolytic when injected directly into the circulation of rabbits and pigeons, and the acute death produced may be ascribed to a massive destruction of red corpuscles. The passage of the fluid portion of glucose broth cultures through Berkefeld filters reduces materially the hemolytic and poisonous effects. Cultures of the Welch bacilli in plain broth to which sterile pigeon or rabbit muscle is added are highly toxic, and the toxicity is not noticeably diminished by Berkefeld filtration. The filtrates are hemolytic when injected intravenously and inflaming and necrotizing when injected subcutaneously and intramuscularly. The local lesions produced in the breast muscles of the pigeon closely resemble those caused by infection with the bacilli. The toxicity of these filtrates is not affected by neutralization with sodium hydroxide, but is materially reduced by heating to 62°C. and entirely removed by heating to 70°C. for 30 minutes. Successive injections of carefully graded doses of this toxic filtrate in pigeons and rabbits give rise to active immunity. The blood taken from the immunized rabbits is capable of neutralizing the toxic filtrate in vivo and in vitro. The filtrate has therefore been designated as toxin and the immune serum as antitoxin. The antitoxin neutralizes the toxin in multiple proportions. Hence the latter would seem to possess the properties of an exotoxin. Moreover, it neutralizes the hemolytic as well as the locally .injurious toxic constituent. Antitoxic serum prepared from a given culture of Bacillus welchii is neutralizing for the toxins yielded by the other four cultures of that microorganism. The antitoxin is protective and curative against infection with the spore and the vegetative stages of Bacillus welchii in pigeons. The limits of the protective and curative action are now under investigation.


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