scholarly journals Notes on the Production of Immunity to Diphtheria Toxin

1921 ◽  
Vol 20 (2) ◽  
pp. 176-220 ◽  
Author(s):  
A. T. Glenny ◽  
H. J. Südmersen

(a) Primary Stimulus. In animals possessing no normal antitoxin a single injection of toxin either “attenuated” or under cover of antitoxin, whether injected previously or at the same time or present in the form of passive immunity maternally transmitted, is followed by a latent period of about three weeks, and the maximum immunity is reached in about eight weeks.(b) Secondary Stimulus. In immune animals, whether naturally immune or artificially immunised, a single injection of toxin or of a toxin-antitoxin mixture is followed by a latent period of about four days and the maximum immunity is reached in about ten days; the great and rapid immunity response to the secondary stimulus offers a striking contrast to the small and gradual response to the primary stimulus.(c) Intermediate Stimulus. In partially immune animals the response to an injection of toxin is in magnitude and rapidity of a character intermediate between the responses following a primary and a secondary stimulus.

1955 ◽  
Vol 53 (2) ◽  
pp. 172-179 ◽  
Author(s):  
J. H. Mason ◽  
Mary Robinson ◽  
P. Agerholm Christensen

SummaryGroups of guinea-pigs were passively immunized against diphtheria toxin with homologous antitoxic serum so that their sera contained, at the start of the experiment, 1·0, 0·1, 0·01 or 0·001 unit/ml, respectively. They were then actively immunized with one, or two spaced, injections of 0·1 Lf of A.D.F. Two control groups were included, one passively immunized only and the other actively immunized only.Passively produced serum titres of 0·01 and 0·001 unit/ml. did not interfere with active immunization in any demonstrable way.A titre of 0·1 unit/ml. did interfere with active immunization, markedly 4 weeks after the primary, slightly 2 weeks after the secondary, and markedly 14 weeks after the secondary, stimulus.A titre of 1·0 unit/ml. interfered with active immunization, markedly 4 weeks after the primary, and 2 and 14 weeks after the secondary, stimulus. This titre, however, did not completely annul the effect of the primary stimulus. The highest observed serum titre was obtained at the 32nd, instead of at the 4th week, as in the guinea-pigs actively immunized only.In large measure the results confirm those of Barr and her colleagues who found that, in human babies, an initial ‘passive’ titre of 0·04 unit/ml. serum did not interfere with active immunization, whereas a titre of 0·1 unit/ml, led to unsatisfactory immunization.


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.


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.


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


1962 ◽  
Vol 155 (961) ◽  
pp. 551-556 ◽  

The distribution of antibody activity in the protein fractions of immune hedgehog serum was studied. Following a single immunizing injection of Brucella abortus suspension about 80% of the immunological activity is located in the β -globulin fraction, and the remainder in the γ -globulin. With prolonged immunization there is no appreciable increase in the serum agglutinin titre, and the antibody activity is still predominantly in the β -globulin fraction (62%) and the remainder in the γ -globulin. Following a single injection of Salmonella pullorum the antibody activity is fairly evenly spread between the β - and γ -globulins, but with prolonged immunization the serum titre is greatly increased and about 80% of the activity of these high titre sera is located in the γ -globulin component. The significance of the distribution of antibody activity in the sera is discussed in relation to the postnatal transmission of passive immunity in this species.


1925 ◽  
Vol 24 (3-4) ◽  
pp. 301-320 ◽  
Author(s):  
A. T. Glenny

When diphtheria toxin is injected in a suitable form and in sufficient quantity into an animal, antitoxin will presently appear in the blood. If the injection be made into an animal that has not previously received a stimulus there is a latent period of about three weeks before any antitoxin can be detected. The amount present in the blood gradually increases, reaching a maximum about eight weeks after the injection, and then a gradual fall in level of antitoxic content is seen. If, however, the same amount of the same antigen be injected into a previously treated animal, antitoxin appears in the circulation at a far greater rate. The latent period is only three days, and the maximum antitoxin level is reached in about eight days. The maximum level reached is from 10 to 100 times that reached after an injection into a normal animal. The two types of response are illustrated in Charts 1 and 2 and also in Chart 3, which shows the antitoxic content of a horse after two separate injections of a toxin antitoxin mixture. There is a great contrast between the extent and rapidity of the antitoxic response on the two occasions.


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.


1968 ◽  
Vol 27 (1) ◽  
pp. 219-230
Author(s):  
Donald Stewart Leventhal

Stimulus generalization was hypothesized to represent the outcome of a perceptual (for primary stimulus generalization) or conceptual (for secondary stimulus generalization) categorization process. Perception and conception were distinguished by differential speed and locus of action and by varying susceptibility to irrelevant and redundant information. Within a semantic generalization paradigm, S's right forearm muscle potentials to semantic and homographic generalization words were recorded. Time interval and stimulus display characteristics of the presentations of the generalization word were varied. Results indicated little support for the view of stimulus generalization as a categorization process. There was, however, support for the differential susceptibility of perception and conception to variations in stimulus display characteristics.


1951 ◽  
Vol 93 (2) ◽  
pp. 161-171 ◽  
Author(s):  
Harold S. Ginsberg ◽  
Frank L. Horsfall

Inhibition of the multiplication of PVM by the capsular polysaccharide of Friedländer bacillus, type B, is associated with restriction in the development of pneumonia induced with the virus in the mouse lung. The extent of the pneumonic process appears to be a function of the degree of viral multiplication; the greater the inhibition of multiplication, the less extensive is the pneumonia and the more probable is the recovery of animals treated with the polysaccharide. Effective therapy of pneumonia induced in mice with PVM is obtained with a single injection of 0.02 mg. of the substance given intranasally either 2 or 3 days after inoculation. Under appropriate conditions, treated animals recover completely from a viral infection which is, in control animals, uniformly fatal. The polysaccharide produces inhibition if given in the first two-thirds of the latent period of the multiplication cycle, i.e., within 10 hours, but is ineffective when given at 12 hours or later. However, the second cycle and subsequent cycles are inhibited irrespective of the time the substance is injected during the first cycle of multiplication. The findings are discussed in relation to a theory regarding the mechanism of action of the polysaccharide.


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.


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