scholarly journals Duration of Passive Immunity. Part III

1923 ◽  
Vol 22 (1) ◽  
pp. 37-51 ◽  
Author(s):  
A. T. Glenny ◽  
Barbara E. Hopkins

1. The course of disappearance of passive immunity in rabbits injected with diphtheria antitoxin obtained from goats, men, guinea-pigs and cows, consists of the same three phases that follow the injection of horse serum.2. The rabbits examined were more responsive to goat, human and guinea-pig serum than to horse and cow serum.3. The course of disappearance of passive immunity in rabbits, horses and guinea-pigs injected with homologous antitoxin, consists of Phases A and B only, and Phase B is far slower than when heterologous serum is injected into rabbits.4. Sheep and goats eliminate antitoxin obtained from a horse at a very slow rate, and Phase C is hardly detectable.5. Natural immunity of horses to diphtheria toxin is gradually acquired by a number of increasing responses to external stimuli.

1959 ◽  
Vol 57 (2) ◽  
pp. 227-234
Author(s):  
D. A. Long

Highly purified crystalline diphtheria toxin-protein, and toxoid prepared from it, were labelled with 131I, without change of potency, and injected intradermally into immune and allergic guinea-pigs. It is probable that actively immunized guinea-pigs localize these antigens and that localization is due to hypersensitivity of a type that cannot be transferred with serum; it is possibly of the delayed (tuberculin-type) of allergy.It is a pleasure to acknowledge the gift of highly purified (crystalline) diphtheria toxin, and toxoid prepared from it, from Dr C. G. Pope of the Wellcome Research Laboratories, England. Dr S. P. Masouredis of the Central Blood Bank of Pittsburgh kindly labelled these antigens, using the technique he devised. Dr W. J. Kuhns generously provided the human precipitating and non-precipitating diphtheria antitoxin*.The collimator head was made by Mr J. Nechaj of the University of Pittsburgh.All these collaborators gave me advice on matters of which I was ignorant; for this I am grateful.


1912 ◽  
Vol 12 (1) ◽  
pp. 64-76 ◽  
Author(s):  
H. J. Südmersen ◽  
A. T. Glenny

1. A male guinea-pig which has received a single injection of a mixture of diphtheria toxin-antitoxin causing severe constitutional disturbance, may beget offspring of slightly lower resistance than normal to diphtheria toxin2. This effect is generally restricted to young born within twelve months after the injection of the father, being rarely noticed in the young of later litters.3. An increased susceptibility to diphtheria toxin is likewise observed in the offspring of male or female guinea-pigs which have received a large dose of horse serum. The greater susceptibility to diphtheria toxin of the young of male guinea-pigs which have been treated with toxin-antitoxin may therefore be non-specific in character.4. The injection of diphtheria toxin-antitoxin mixtures into guinea-pigs whether male or female reduces their rate of breeding and lowers the vitality of their young.5. These effects are most pronounced when the toxin-antitoxin mixture produces severe constitutional disturbance or contains excess of horse serum


1914 ◽  
Vol 20 (1) ◽  
pp. 37-51 ◽  
Author(s):  
James W. Jobling ◽  
William Petersen

1. The unsaturated lipoids (serum antitrypsin) can be adsorbed from guinea pig serum, rabbit serum, and horse serum by kaolin, starch, agar, and bacteria. 2. Diphtheria toxin and cobra venom also reduce the serum antitrypsin, possibly because of their affinity for lipoids. 3. Anaphylatoxins represent sera rendered toxic by partial removal of serum antitrypsin. 4. The matrix of the protein split products lies in the serum proteins so exposed. 5. The amount of removal of serum antitrypsin depends on definite quantitative relations; very large amounts and very small amounts of adsorbing substances are least effective (kaolin, starch, and bacteria). 6. Bacteria previously treated with serum or with oils do not adsorb serum antitrypsin. 7. Bacteria treated with serum become more resistant to the action of trypsin.


Many experimenters have endeavoured to isolate diphtheria antitoxin from fludis containing it. In 1893 Brieger and Ehrlich (1) investigated the properties of milk obtained from animals which had been immunised against diphtheria toxin. This milk contained an appreciable amount of antitoxin which could be precipitated between 27- and 38-per-cent. ammonium sulphate. By this method they were able to increase the antitoxic value of their fluid about five hundred times. But in milk only two proteins are present which differ widely in their physical properties—caseinogen and lact albumin—and their results could not be extended to horse serum, which is the main source of diphtheria antitoxin. Their experiments did not show that antitoxin is not a protein.


1911 ◽  
Vol 11 (2) ◽  
pp. 220-234 ◽  
Author(s):  
H. J. Südmersen ◽  
A. T. Glenny

1. Diphtheria toxin-antitoxin mixtures induce a higher immunity in guinea-pigs than sub-lethal doses of toxin; one injection of the mixture being sufficient to produce an immunity lasting in some cases for a period of over two years, as shown by the passive immunity conferred on the offspring.2. The highest immunity is produced by toxin-antitoxin mixtures containing the most uncombined toxoid.3. The active immunity of the mother is transferred passively to the offspring.4. The passive immunity thus transferred usually disappears at the end of two months after birth, and only in rare instances has been recongnised after three months.5. Immunity is mainly transmitted in utero, and only to a slight extent during lactation.6. Young bred from does that have been used for a single routine antitoxin test may be able to tolerate 14 times the does of diphtheria toxin fatal for a normal guinea-pig.


1936 ◽  
Vol 64 (5) ◽  
pp. 673-687 ◽  
Author(s):  
Hans Zinsser ◽  
Attilio Macchiavello

1. Guinea pigs can be actively immunized against European typhus fever with homologous formalinized Rickettsia tissue cultures, provided sufficient amounts are injected. The method is suggested for practical application in man. 2. Serovaccination against European typhus fever can be successfully applied to guinea pigs by a variety of methods, the simplest of which consists of the injection of mixtures of virulent defibrinated guinea pig blood and convalescent guinea pig serum taken from 3 to 5 days after defervescence. Similar results can be obtained with mixtures in which tissue culture virus, either with convalescent guinea pig serum or with antimurine horse serum, is used. There is no indication so far that such animals become carriers. Possible application of these methods to typhus epidemics is discussed.


1911 ◽  
Vol 11 (3) ◽  
pp. 423-442 ◽  
Author(s):  
H. J. Sudmersen ◽  
A. T. Glenny

(1) The young of parents both of which have been injected with an immunising mixture of diphtheria toxin and antitoxin, show immunity of the same order as that of young from similarly treated mothers and normal fathers.(2) The injection of certain foreign substances into a female guinea-pig appears to have a direct effect on the offspring in diminishing their resistance to diphtheria toxin, shown equally well by the young of mothers injected, (a) before the attainment of sexual maturity, (b) during pregnancy, and (c) after birth during the period of lactation.(3) A single injection of diphtheria toxin may give rise to a condition of active immunity (as tested by the resistance of the young) in guinea-pigs possessing hereditarily transmitted passive immunity. Should this injection of toxin give rise to great constitutional disturbance, the young may show lowered resistance, whereas, if it give rise to but slight constitutional disturbance, the young show a high degree of immunity. These effects appear to be accentuated if similar injections are repeated in the next generation.


1923 ◽  
Vol 22 (1) ◽  
pp. 12-36 ◽  
Author(s):  
A. T. Glenny ◽  
Barbara E. Hopkins

1. Normal rabbits injected intravenously with diphtheria antitoxin obtained from a horse vary considerably both in regard to the duration of Phase B and the duration and the intensity of Phase C.2. Phase C, the phase of accelerated loss due to formation of precipitin appears sooner and is more pronounced in older rabbits.3. The early appearance and more rapid formation of antibody (precipitin) in certain rabbits is indicative of naturally acquired immunity.4. The highest concentration in the blood of rabbits injected subcutaneously with antitoxic horse serum is seen after 2 to 3 days, when it reaches approximately the same value as that of rabbits injected intravenously, and represents only one-third of the total antitoxin injected. Two hours after subcutaneous injection the antitoxic content is only one two-hundredth of that of a rabbit injected intravenously.


Diphtheria antitoxin prepared in the horse and refined by peptic digestion when injected in very large doses into women in an advanced stage of pregnancy did not pass to the infant. In pregnant guinea-pigs diphtheria antitoxin (naturalserum, ex -guinea-pig) passed to the young in abundance; but, after peptic-digestion, this homologous antitoxin failed entirely to pass the placenta, the young being devoid of antitoxin at birth. The passage was not affected by the treatment of the natural serum with ammonium sulphate as used in the Gibson-Banzhaf (1910) process for the concentration of antitoxin. Diphtheria antitoxin (natural serum ex -horse) passed from pregnant guinea-pigs to their off spring in smaller amounts and much less readily than homologous antitoxin, and the quantity of antitoxin( ex -horse) so passing was reduced even further and very considerably as a result of peptic digestion. Even under the most favourable conditions homologous antitoxin takes sometime (2 or 3 days) to attain the same concentration in the young as in the mother; but once this concentration has been attained it is preserve data high level for long periods. Passive anaphylactics ensitization of guinea-pigs, either of the whole animal or the isolated uterus, is easily effected, in vivo or in vitro , by small quantities of diphtheria antitoxin (either natural serum or ammonium sulphate concentrated, ex -guinea-pig), but this property is completely lost when the homologous antitoxin is subjected to peptic digestion. It is not possible to sensitize anaphylactically guinea-pigs, in vivo or in vitro , by means of diphtheria antitoxin, ex -horse, whether the antibody is presented either in the form of natural serum, or concentrated by means of ammonium sulphate; and the result is the same when pepsin-refined diphtheria antitoxin ex -horse is used. When 5 or 10 units of diphtheria antitoxin ex -horse, whether as natural serum, ammonium-sulphate concentrated or pepsin-refined, are injected subcutaneously into guinea-pigs, the animals are rendered Schick-negative in a few hours. These antitoxins are eliminated in about a week, after which time the injected guinea-pigs are found to be Schick-positive again. If, however, the same amounts of antitoxin made in guinea-pigs are injected into guinea-pigs the result is different; the animals also become Schick-negative, but this condition is maintained for a month or longer. That is, homologous antitoxin is eliminated much more slowly; but if this natural serum antitoxin from the guinea-pig is subjected to peptic digestion it is eliminated as quickly as diphtheria antitoxin made in the horse. When diphtheria toxin is injected intracutaneously into guinea-pigs, a quantity of diphtheria antitoxin 50,000 times as large as that required to neutralize it in vitro is required for neutralization in the animal, and then only if injected intravenously within 1hr.; but little or no neutralization in vivo occurs if the intravenous injection is longer delayed, whatever type of homologous or heterologous antitoxin is administered.


1934 ◽  
Vol 60 (6) ◽  
pp. 661-668 ◽  
Author(s):  
Jules Freund

1. Filtrates from B. coli, B. typhosus, or meningococci injected into the skin of guinea pigs do not produce visible inflammation. When these injections are followed by intravascular injections of the same material, hemorrhages do not occur in the skin. 2. Guinea pigs sensitized to horse serum react with redness and edema to 0.1 or 0.01 cc. of horse serum injected into the skin, and subsequent intravascular injection of typhoid filtrate does not produce hemorrhage at the site of the reaction to horse serum. 3. When guinea pigs are injected into the skin with diphtheria toxin and these injections are followed by intravascular injection of filtrates from B. typhosus, hemorrhage occurs in the skin at the site of the reaction to diphtheria toxin. 4. When silver nitrate is injected into the skin of guinea pigs, redness, edema, and necrosis follow, and in a few guinea pigs small areas of hemorrhage can also be noticed. About half of the guinea pigs that have received an intravascular injection of typhoid filtrate react with hemorrhage at the site of the injection of silver nitrate.


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