scholarly journals Immunity of Guinea-Pigs to Diphtheria Toxin and its Effect upon the Offspring

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.

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


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.


1925 ◽  
Vol 41 (1) ◽  
pp. 53-64 ◽  
Author(s):  
George M. Mackenzie ◽  

1. Intraperitoneal injections of killed and living broth cultures of a virulent pneumococcus produce in guinea pigs a high degree of active immunity and a serum with strong protective power. 2. Despite the protective power of such serum no agglutinins for the homologous organism and no precipitins for soluble derivatives were demonstrable. 3. Guinea pig immunity to pneumococcus infection produced by the method described is not attended by cutaneous allergy to derivatives of the pneumococcus used for immunization. 4. During the course of an artificially produced active immunity, anaphylaxis may at times be present and at times absent without any measurable effect upon the resistance of the animal to infection by intraperitoneal injection. 5. In the particular instance studied, the experiments indicate that anaphylaxis to pneumococcus protein has no important effect upon the resistance of the animal to infection. It appears to be a concomitant without any significant rôle in the immunity mechanism.


1922 ◽  
Vol 21 (1) ◽  
pp. 104-111 ◽  
Author(s):  
A. T. Glenney ◽  
K. Allien

The injection of the small amount of diphtheria toxin used in the Schick test may act as a secondary stimulus.A Schick test may therefore cause a great and rapid increase in the immunity of the animals tested.Examples are quoted of six rabbits and twelve guinea-pigs in Tables II to VII.2. A fraction of a Schick dose may act as a secondary stimulus. Rabbit G 23 quoted in Table IV, injected with 1/10 of a Schick dose, showed an immunity response, the antitoxic content of its blood rising from 1/50 to nearly 1/10 unit per c.c. in six days.3. The action of a Schick dose as a secondary stimulus may cause an animal to give a negative reaction when tested seven days or more after the first positive reaction.This is illustrated by rabbits G 7 in Table III, G 31 in Table II, G 32 and G 34 in Table V and four guinea-pigs in Table VI.4. The antigenic value of a Schick dose of toxin as a secondary stimulus may be as high as that of a reasonable dose of a toxin-antitoxin mixture suitable for human immunisation. Examples are given comparing the results of the injection of a Schick dose of toxin and of a toxin-antitoxin mixture in the same rabbit in Table III, in different rabbits, G 20 and G 22 in Table IV and reference is made to the companion rabbits to those quoted in Table V.5. The antigenic value of a Schick dose as a secondary stimulus can be demonstrated:A. In animals which have not produced a detectable quantity of antitoxin (that is less than 1/2000 of a unit per c.c.) as the result of a primary stimulus.See both rabbits in Table II, rabbit G 20 in Table IV, both rabbits in Table V, and guinea-pig FF 19. v in Table VII. The four guinea-pigs in Table VI probably come under the same heading.B. In animals whose actively produced antitoxin has fallen below a de tectable level.See rabbit G 7 in Table III.(These results add further confirmation to the phenomenon reported in the paper “Active immunity to diphtheria in the absence of detectable antitoxin” (Glenny and Allen, 1922).6. A Schick dose of toxin which gives a positive reaction may, by acting as a secondary stimulus, produce a rapid increase in the antitoxic value of animals already containing some actively produced antitoxin.See guinea-pig LL 17. vi in Table VII.7. A Schick dose of toxin which causes no reaction may, by acting as a secondary stimulus, produce a rapid increase in the antitoxic value of animals already containing some actively produced antitoxin.See guinea-pigs in Table VII.8. A Schick dose of toxin may fail as a secondary stimulus if the antitoxic content at the time of injection is comparatively high.See rabbit G 21 in Table IV.


1931 ◽  
Vol 53 (6) ◽  
pp. 821-826 ◽  
Author(s):  
Augustus Wadsworth ◽  
Ella N. Hoppe

As determined by the intracutaneous test in guinea pigs, diphtheria toxin is not altered in the presence of cardiac tissue obtained from the fetal or from the adult heart of the guinea pig. Tissue cultures were apparently uninjured by the presence of the toxin in the dilutions used in these experiments, and, when washed with embryo extract after removal of the diluted toxin, continued to grow. Embryonic guinea pig cardiac muscle tissue growing in cultures in vitro possesses the power of neutralizing, binding, or destroying diphtheria toxin so that it is no longer toxic for normal guinea pigs. Such neutralization takes place through the intervention of growing tissue and is a property which is lacking in similar surviving tissue not in a state of cultivation. Thus, it appears that the living, growing cells of the tissues neutralize or destroy limited quantities of toxin; only when the quantity of toxin exceeds a certain limit is its action injurious.


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.


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.


1909 ◽  
Vol 9 (4) ◽  
pp. 399-408 ◽  
Author(s):  
H. J. Sudmersen ◽  
A. T. Glenny

1. A larger dose of toxin is necessary to kill a guinea-pig of the same weight in summer than in winter.2. The rate of growth of guinea-pigs is more rapid in the summer months.3. The weights of guinea-pigs are least affected by lethal doses in summer.4. For guinea-pigs of the same weight the fatal dose increases with the age.


1970 ◽  
Vol 47 (2) ◽  
pp. 225-230 ◽  
Author(s):  
K. P. BLAND ◽  
B. T. DONOVAN

SUMMARY Regression of the corpora lutea in the guinea-pig could be accelerated by treatment with 10 μg. oestradiol benzoate daily over days 3–11 of the oestrous cycle. A single injection of 10 μg. oestradiol benzoate on day 3 was also effective. The luteolytic effect of oestrogen was abolished by hysterectomy, indicating that the uterus is involved in the mediation of the response. Progesterone (5 mg. daily over days 3–11) enhanced the luteal regression brought about by the presence of two glass beads in one horn of the uterus, but did not affect luteal size in otherwise intact females. Treatment of guinea-pigs with 5 mg. progesterone daily over days 2–5 or 4–7 failed to alter the length of the oestrous cycle.


1922 ◽  
Vol 21 (1) ◽  
pp. 96-99 ◽  
Author(s):  
A. T. Glenny ◽  
K. Allen

1. For the particular toxin tested, the intravenous m.l.d. for mice was 60 times and the intramuscular m.l.d. for mice 100 times, the guinea-pig sub cutaneous m.l.d.2. Antitoxin has the same neutralising power for toxin in mice as in guinea-pigs.


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