scholarly journals Some Fundamental Experiments on Immunity, Illustrated

1904 ◽  
Vol 4 (1) ◽  
pp. 31-72 ◽  
Author(s):  
E. F. Bashford
Keyword(s):  
Lethal Dose ◽  
Test Tube ◽  
Immune Serum ◽  
Normal Serum ◽  
Weight Of Evidence ◽  
Passive Immunity ◽  
Artificial Immunity ◽  
The Difference

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.

scholarly journals A SPECIFIC POISON IN THE LIVER EXTRACTS OF RABBITS INOCULATED WITH TYPHOID AND PRODIGIOSUS BACILLI INTRAVENOUSLY

1918 ◽  
Vol 28 (5) ◽  
pp. 571-583
Author(s):  
Julia T. Parker
Keyword(s):  
Anaphylactic Shock ◽  
Liver Extract ◽  
Lethal Dose ◽  
Toxic Substance ◽  
Normal Liver ◽  
Immune Serum ◽  
Minimum Lethal Dose ◽  
Lethal Doses

1. The livers of rabbits inoculated with cultures of Bacillus typhosus or Bacillus prodigiosus under certain conditions contain a toxic substance extractable with salt solution. When the toxic extracts are injected intravenously into normal rabbits the latter animals develop symptoms resembling those of anaphylactic shock and succumb. The lethal doses of the toxic extracts are far smaller than those of normal liver extract. 2. The livers of rabbits injected with typhoid antigen also yield a toxic extract. 3. Boiling as well as filtration through a Berkefeld filter only partially detoxicates the extract. 4. Tolerance to one to two lethal doses of the poisonous extracts can be induced by cautious immunization. 5. Rabbits actively immunized to Bacillus typhosus or Bacillus prodigiosus usually resist one lethal dose of the homologous liver poison; and animals tolerant to the typhoid liver poison resist one minimum lethal dose at least of Bacillus typhosus. 6. Typhoid immune serum is not detoxicating either in vivo or in vitro for the typhoid liver poison. 7. The liver poisons are specific, since rabbits actively immunized to either Bacillus typhosus or Bacillus prodigiosus withstand at least one minimum lethal dose of the homologous but not of the heterologous-liver poisons.

scholarly journals PneumococcalSurface Protein A Is Expressed In Vivo, and Antibodies to PspA AreEffective for Therapy in a Murine Model of PneumococcalSepsis

2003 ◽  
Vol 71 (12) ◽  
pp. 7149-7153 ◽  
Author(s):  
E. Swiatlo ◽  
J. King ◽  
G. S. Nabors ◽  
B. Mathews ◽  
D. E. Briles
Keyword(s):  
Northern Blot Analysis ◽  
Lethal Dose ◽  
Protein A ◽  
Surface Protein ◽  
Immune Serum ◽  
Invasive Infection ◽  
Pneumococcal Infections ◽  
Type 3

ABSTRACT Pneumococcal surface protein A (PspA) is an immunogenic protein expressed on the surface of all strains of Streptococcus pneumoniae (pneumococcus) and induces antibodies which protect against invasive infection in mice. Pneumococci used for infectious challenge in protection studies are typically collected from cultures grown in semisynthetic medium in vitro. The purpose of these studies is to confirm that PspA is expressed by pneumococci during growth in vivo at a level sufficient for antibodies to PspA to be protective. Mice were actively immunized with purified PspA or by passive transfer of monoclonal antibody (MAb) and challenged with a capsular type 3 strain in diluted whole blood from bacteremic mice. All were protected against challenge with 10 times the 50% lethal dose (LD50), and mice challenged with 1,000 times the LD50 had increased survival compared with controls. Additionally, nonimmune mice treated with MAbs to PspA or PspA immune serum at 6 and 12 h after infection with 10 times the LD50 also showed increased survival. Northern blot analysis of RNA from pneumococci grown either in vitro or in vivo showed similar levels of PspA mRNA. These results demonstrate that PspA is expressed in vivo in a mouse model and that immunization with PspA induces antibodies to an antigen which is expressed during the course of invasive infection. Immunotherapy with antibodies to PspA may have some utility in treating pneumococcal infections in humans.

scholarly journals THE OCCURRENCE OF DEGRADED PNEUMOCOCCI IN VIVO

1927 ◽  
Vol 45 (5) ◽  
pp. 807-814 ◽  
Author(s):  
Hobart A. Reimann
Keyword(s):  
Natural Infection ◽  
Blood Stream ◽  
Test Tube ◽  
Normal Serum ◽  
The Body ◽  
Slight Variation ◽  
Pure Cultures ◽  
Heterologous Serum

It is conceivable that a change from the virulent, non-phagocytable S form of Pneumococcus to the avirulent phagocytable R form may take place in pneumococcus disease, but the experiments here reported do not settle the question whether or not this is an important factor in determining the outcome in natural infection. It has been shown experimentally that the degradation from the S form to the R form actually does take place in cultures of Pneumococcus growing in agar subcutaneously embedded in guinea pigs, in agar enclosed in vials subcutaneously embedded in rabbits, and spontaneously in the blood stream of infected horses. However, it was not possible in any of the experiments here cited to demonstrate the complete change from S to R pneumococci before the bacteria disappeared from the body. When the intermediate or R forms did appear, they were always accompanied and usually exceeded in number by the S forms and all three forms disappeared together. S organisms may disappear entirely without evidence of first going through the intermediate and R stages. On the other hand, contrary to expectations, pure cultures of R forms remained viable in subcutaneous foci for weeks although apparently freely accessible to the action of phagocytes. It seems of some significance that the R forms appeared early in the vials (inoculated with S pneumococci) in immunized and normal rabbits alike, indicating that the presence of demonstrable specific immune bodies was not alone responsible for the variation of the bacteria. Of some importance also is the fact that R forms were never derived from similarly prepared control cultures growing in vitro at the same temperature and immersed in normal serum, although the S forms remained viable and unaltered for 6 weeks. It is likely that variations of pneumococci do not occur readily when S cultures are exposed to normal serum in vitro, especially when growing in closed vials under a diminished oxygen supply, for it has previously been shown (2) that only slight variation occurs even after prolonged (240) transfers in heterologous serum broth in the test-tube. It is possible, therefore, that the variation which occurred among pneumococci growing in agar vials embedded in normal rabbits was actually provoked by unknown influences in the living tissue fluids. Although R forms have been shown to occur in vivo, no positive evidence can be derived from these experiments to prove that recovery from pneumococcus infection depends upon the degradation of the virulent S forms of pneumococci to the avirulent R forms and the subsequent destruction of the latter by phagocytes.

scholarly journals LOCAL PASSIVE IMMUNITY IN THE SKIN OF RABBITS TO INFECTION WITH (1) A FILTERABLE VIRUS, AND (2) HEMOLYTIC STREPTOCOCCI

1925 ◽  
Vol 41 (2) ◽  
pp. 185-194 ◽  
Author(s):  
Thomas M. Rivers ◽  
William S. Tillett
Keyword(s):  
Normal Skin ◽  
Immune Serum ◽  
Normal Serum ◽  
Passive Immunity ◽  
Small Areas ◽  
Local Protection ◽  
Refractory State ◽  
The Difference

Small areas of skin infiltrated with immune serum proved refractory to the injurious action of a filterable rabbit virus inoculated 24 to 48 hours later. Infiltrations of normal serum did not appreciably protect the skin against the virus. The local protection afforded by the infiltrations of immune serum appears to constitute an example of local passive immunity. Small areas of skin infiltrated with either normal serum or meat infusion broth proved more refractory than normal skin to infection with hemolytic streptococci inoculated 24 hours later. The refractory state induced in the tissues was non-specific in character. A greater amount of local protection against hemolytic streptococci was afforded by infiltrations with a homologous immune serum than by infiltrations with normal serum. The difference in the amount of protection afforded by immune serum over that induced by normal serum may be thought of as representative of the degree of local passive immunity conferred.

scholarly journals STUDIES ON THE MECHANISM OF IMMUNITY IN TUBERCULOSIS

1942 ◽  
Vol 75 (3) ◽  
pp. 247-268 ◽  
Author(s):  
Max B. Lurie ◽  
Keyword(s):  
Normal Animal ◽  
Immune Serum ◽  
Body Fluids ◽  
Normal Serum ◽  
Active Tuberculosis ◽  
Mononuclear Phagocytes ◽  
Tubercle Bacillus ◽  
Normal Cells

1. Mononuclear phagocytes of immunized animals that had ingested tubercle bacilli in vivo and had subsequently been transplanted and grown in the environment of a normal animal continue to inhibit the multiplication of the microorganism in their cytoplasm in the absence of immune body fluids. 2. Mononuclear phagocytes of immunized animals that had ingested tubercle bacilli in vitro in the presence of immune serum inhibit the multiplication of the microorganism in their cytoplasm to a much greater extent than cells of normal animals that had ingested the bacteria in the same medium and had grown in a similar environment. 3. The presence of immune serum during the in vitro ingestion of tubercle bacilli by mononuclear phagocytes of normal animals does not regularly endow them with increased bacteriostatic properties for the microorganism. Whether or not continued sojourn of normal cells in immune body fluids will confer upon them such properties has not been determined. 4. Mononuclear phagocytes of immunized animals that had ingested tubercle bacilli in vitro in a medium of normal serum and had subsequently grown in an environment devoid of immune body fluids inhibit the multiplication of the microorganism in their cytoplasm to a much greater extent than do normal cells under the same conditions. 5. Active tuberculosis confers on the mononuclear phagocytes themselves increased bacteriostatic properties for the tubercle bacillus which are independent of the immune body fluids or of the organ environment in which they grow.

Enhancement of ADP-induced Platelet Aggregation by Adrenaline in Vivo and Its Prevention

1973 ◽  
Vol 29 (02) ◽  
pp. 490-498 ◽  
Author(s):  
Hiroh Yamazaki ◽  
Itsuro Kobayashi ◽  
Tadahiro Sano ◽  
Takio Shimamoto
Keyword(s):  
Platelet Count ◽  
Platelet Aggregation ◽  
Platelet Rich Plasma ◽  
The Other ◽  
Endothelial Surface ◽  
Important Interaction ◽  
Blood Coagulability ◽  
The Difference

SummaryThe authors previously reported a transient decrease in adhesive platelet count and an enhancement of blood coagulability after administration of a small amount of adrenaline (0.1-1 µg per Kg, i. v.) in man and rabbit. In such circumstances, the sensitivity of platelets to aggregation induced by ADP was studied by an optical density method. Five minutes after i. v. injection of 1 µg per Kg of adrenaline in 10 rabbits, intensity of platelet aggregation increased to 115.1 ± 4.9% (mean ± S. E.) by 10∼5 molar, 121.8 ± 7.8% by 3 × 10-6 molar and 129.4 ± 12.8% of the value before the injection by 10”6 molar ADP. The difference was statistically significant (P<0.01-0.05). The above change was not observed in each group of rabbits injected with saline, 1 µg per Kg of 1-noradrenaline or 0.1 and 10 µg per Kg of adrenaline. Also, it was prevented by oral administration of 10 mg per Kg of phenoxybenzamine or propranolol or aspirin or pyridinolcarbamate 3 hours before the challenge. On the other hand, the enhancement of ADP-induced platelet aggregation was not observed in vitro, when 10-5 or 3 × 10-6 molar and 129.4 ± 12.8% of the value before 10∼6 molar ADP was added to citrated platelet rich plasma (CPRP) of rabbit after incubation at 37°C for 30 second with 0.01, 0.1, 1, 10 or 100 µg per ml of adrenaline or noradrenaline. These results suggest an important interaction between endothelial surface and platelets in connection with the enhancement of ADP-induced platelet aggregation by adrenaline in vivo.

Reliability of a Single β-Thromboglobulin Measurement in a Diabetic Population : Importance of PGE1 in Anticoagulant Mixture

1987 ◽  
Vol 57 (02) ◽  
pp. 201-204 ◽  
Author(s):  
P Y Scarabin ◽  
L Strain ◽  
C A Ludlam ◽  
J Jones ◽  
E M Kohner
Keyword(s):  
In Vitro Release ◽  
Mean Value ◽  
Reliable Estimate ◽  
Diabetic Patients ◽  
Single Measurement ◽  
Diabetic Population ◽  
The Difference ◽  
Vitro Release

SummaryDuring the collection of samples for plasma β-thromboglobulin (β-TG) determination, it is well established that artificially high values can be observed due to in-vitro release. To estimate the reliability of a single β-TG measurement, blood samples were collected simultaneously from both arms on two separate occasions in 56 diabetic patients selected for a clinical trial. From each arm, blood was taken into two tubes containing an anticoagulant mixture with (tube A) and without (tube B) PGE!. The overall mean value of B-TG in tube B was 1.14 times higher than in tube A (p <0.01). The markedly large between-arms variation accounted for the most part of within-subject variation in both tubes and was significantly greater in tube B than in tube A. Based on the difference between B-TG values from both arms, the number of subjects with artifically high B-TG values was significantly higher in tube B than in tube A on each occasion (overall rate: 28% and 14% respectively). Estimate of between-occasions variation showed that B-TG levels were relatively stable for each subject between two occasions in each tube. It is concluded that the use of PGEi decreases falsely high B-TG levels, but a single measurement of B-TG does not provide a reliable estimate of the true B-TG value in vivo.

Hepato- and Nephroprotective Effects of the Polyphenol Concentrate From Cabernet Sauvignon Grape Varieties Cultivated in Kazakhstan in the Experimental Model Of CCL4-Induced Toxicity

2017 ◽  
Vol 9 (03) ◽  
Author(s):  
Nurgozhin T. ◽  
Sergazy S. H. ◽  
Adilgozhina G. ◽  
Gulyayev A. ◽  
Shulgau Z. ◽  
...  
Keyword(s):  
Carbon Tetrachloride ◽  
Experimental Model ◽  
Lethal Dose ◽  
Radical Scavenging ◽  
Cabernet Sauvignon ◽  
Intragastric Administration ◽  
Liver And Kidney ◽  
Antioxidant Stress

Objective:This study investigates the hepatoprotective effect and the antioxidant role of polyphenol concentrate in the experimental model of carbon tetrachloride (CCl4) induced toxicity. Methods: Antioxidant activity of Cabernet Sauvignon grape polyphenol were evaluated by radical scavenging of 1,1-diphenyl-2-picryl hydrazyl radical (DPPH), 2,2’-azinobis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS.+). In addition, the effects of polyphenol concentrate on the survival of Wistar rats in the toxicity model, was also investigated. The polyphenol concentrate was administered for 5 five days prior to injection of carbon tetrachloride in a sub-lethal dose of 300 mg/kg of animal body weight in order to perform histological examinations of the liver and kidney, and detect the levels of AST, ALT and bilirubin. Results: Administration of polyphenol concentrate increased animal survival in the experimental model. Moreover, the intragastric administration of polyphenol concentrate prior to the initiation of the experimental model of toxicity, which was caused by a sub-lethal CCl4 dose, reduced morphological injuries in the liver and kidney, decreased the AST and ALT levels of the blood serum. Discussion and conclusion: Our data demonstrate that polyphenol concentrate possesses an antioxidant potential both in vitro and in vivo by reducing antioxidant stress that was caused by CCl4 administration into rats.

In Vitro and In Vivo Neutralizing Activity of Uvaria chamae Leaves Fractions on the Venom of Naja nigricollis in Albino Rat and Bovine Blood

2020 ◽  
Vol 14 (4) ◽  
pp. 295-311
Author(s):  
Ada Gabriel ◽  
Mamman Mohammed ◽  
Mohammed G. Magaji ◽  
Yusuf P. Ofemile ◽  
Ameh P. Matthew ◽  
...  
Keyword(s):  
Ethyl Acetate ◽  
Neglected Tropical Diseases ◽  
Lethal Dose ◽  
Positive Control ◽  
Haemolytic Activity ◽  
Cytotoxic Activities ◽  
Albino Rat ◽  
Aqueous Residue

Background: Snakebite envenomation is a global priority ranked top among other neglected tropical diseases. There is a folkloric claim that Uvaria chamae is beneficial for the management of snakebite and wounds in African ethnobotanical surveys. Besides, there are many registered patents asserting the health benefits of U. chamae. Objective: This study aimed to investigate U. chamae’s potentials and identify candidates for the development of tools for the treatment and management of N. nigricollis envenomation. Methods: Freshly collected U. chamae leaves were air-dried, powdered, and extracted in methanol. The median lethal dose of the extract was determined and further fractionated with n-hexane, n-butanol and ethyl acetate. Each fraction was tested for neutralizing effect against venom-induced haemolytic, fibrinolytic, hemorrhagic, and cytotoxic activities. Results: U. chamae fractions significantly (p<0.05) neutralized the haemolytic activity of N. nigricollis venom in n-butanol; 31.40%, n-hexane; 33%, aqueous residue; 39.60% and ethyl acetate; 40.70% at the concentration of 100mg/ml of each fraction against 10mg/ml of the snake venom when compared to the positive control. The fibrinolytic activity of N. nigricollis venom was significantly (p<0.05) neutralized in n-hexane at 73.88%, n-butanol; 72.22% and aqueous residue; 72.22% by the fractions of U. chamae. In addition, haemorrhagic activity of N. nigricollis venom was significantly (p<0.05) neutralized by U. chamae fractions at the concentrations of 100mg/ml, 200mg/ml and 400mg/ml except for n-butanol and aqueous residues at 400 mg/ml. Conclusion: U. chamae leaves fractions possess a high level of protection against N. nigricollis venoms-induced lethality and thus validate the pharmacological rationale for its usage in the management of N. nigricollis envenomation.

scholarly journals Global metabolomic and lipidomic analysis reveals the potential mechanisms of hemolysis effect of Ophiopogonin D and Ophiopogonin D' in vivo

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Huan-Hua Xu ◽  
Zhen-Hong Jiang ◽  
Cong-Shu Huang ◽  
Yu-Ting Sun ◽  
Long-Long Xu ◽  
...  
Keyword(s):  
Chemical Properties ◽  
Principal Component ◽  
Partial Least Square ◽  
Least Square ◽  
Practical Significance ◽  
Plasma Metabolites ◽  
Active Components ◽  
The Difference

Abstract Background OPD and OPD' are the two main active components of Ophiopogon japonicas in Shenmai injection (SMI). Being isomers of each other, they are supposed to have similar pharmacological activities, but the actual situation is complicated. The difference of hemolytic behavior between OPD and OPD' in vivo and in vitro was discovered and reported by our group for the first time. In vitro, only OPD' showed hemolysis reaction, while in vivo, both OPD and OPD' caused hemolysis. In vitro, the primary cause of hemolysis has been confirmed to be related to the difference between physical and chemical properties of OPD and OPD'. In vivo, although there is a possible explanation for this phenomenon, the one is that OPD is bio-transformed into OPD' or its analogues in vivo, the other one is that both OPD and OPD' were metabolized into more activated forms for hemolysis. However, the mechanism of hemolysis in vivo is still unclear, especially the existing literature are still difficult to explain why OPD shows the inconsistent hemolysis behavior in vivo and in vitro. Therefore, the study of hemolysis of OPD and OPD' in vivo is of great practical significance in response to the increase of adverse events of SMI. Methods Aiming at the hemolysis in vivo, this manuscript adopted untargeted metabolomics and lipidomics technology to preliminarily explore the changes of plasma metabolites and lipids of OPD- and OPD'-treated rats. Metabolomics and lipidomics analyses were performed on ultra-high performance liquid chromatography (UPLC) system tandem with different mass spectrometers (MS) and different columns respectively. Multivariate statistical approaches such as principal component analysis (PCA) and orthogonal partial least square-discriminant analysis (OPLS-DA) were applied to screen the differential metabolites and lipids. Results Both OPD and OPD' groups experienced hemolysis, Changes in endogenous differential metabolites and differential lipids, enrichment of differential metabolic pathways, and correlation analysis of differential metabolites and lipids all indicated that the causes of hemolysis by OPD and OPD' were closely related to the interference of phospholipid metabolism. Conclusions This study provided a comprehensive description of metabolomics and lipidomics changes between OPD- and OPD'-treated rats, it would add to the knowledge base of the field, which also provided scientific guidance for the subsequent mechanism research. However, the underlying mechanism require further research.

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