scholarly journals STUDIES ON VIRULENCE

1932 ◽  
Vol 56 (1) ◽  
pp. 13-25 ◽  
Author(s):  
Lloyd D. Felton

From the study of different tissue extracts as media for the growth of pneumococci used in an automatic transfer device, certain inferences are warranted: 1. Media made from calf lung or heart, or from horse skeletal muscle maintain virulence over a long period of time. Conversely, media made from calf spleen lead to a decrease in virulence. 2. Lung medium causes an increase in virulence of seven strains of pneumococci. 3. Virulence is maintained in normal horse serum; but, it rapidly decreases in immune serum, or in pneumococcus antibody solution, a finding which confirms the work of Stryker. Immune serum freed from protective antibody gives results similar to normal serum. 4. Rabbit medium made from the entire animal apparently is less suitable for the maintenance of virulence of pneumococci than medium made in the same way from guinea pig.

1917 ◽  
Vol 25 (4) ◽  
pp. 499-505 ◽  
Author(s):  
Simon Flexner ◽  
Harold L. Amoss

The cerebrospinal fluid taken very early and quite late in the course of acute poliomyelitis exhibits no neutralizing action on filtered poliomyelitic virus. The blood serum on the 6th day of the disease already contains the neutralizing principles. The injection of sterile horse serum into the cerebrospinal meninges in monkeys increases their permeability, so that they permit the immunity neutralizing principles passively injected into the blood to pass into the cerebrospinal fluid. The passage in passively immunized monkeys takes place during a relatively brief space of time and apparently only while the inflammatory reaction produced by the horse serum is at its height. It is established for monkeys and rendered probable for man that the intraspinal injection of immune serum in poliomyelitis is curative. In monkeys normal serum exerts no such action, and at present nothing can be stated definitely regarding the therapeutic effect of normal serum in man except that probably any benefits which may arise from its employment would be attributable not to the action of the serum as such, but to the escape of circulating immunity principles in the blood made possible by the aseptic inflammation set up by it in the meninges. As the immunity principles appear in the blood only after several days, and the reported favorable effects of the immune serum treatment relate to the first days of illness, the employment of normal serum is thus not indicated, while that of an immune serum is.


1919 ◽  
Vol 29 (6) ◽  
pp. 597-603 ◽  
Author(s):  
Harold L. Amoss ◽  
Frederick Eberson

Agglutinins for the meningococcus were not found in the spinal fluid of normal monkeys which had received antimeningococcic serum intravenously. The intraspinal injection of isotonic salt solution, normal horse serum, or a culture of living meningococci allows agglutinins for the meningococcus to pass from the blood to the spinal fluid of the passively immunized monkey; and the rate of the passage is affected by the severity of the inflammation induced in the meninges. The rates of elimination from the blood and spinal canal of meningococcic antibodies, as shown by the agglutination reaction, were compared in monkeys treated with immune serum (a) intraspinally, (b) intravenously, and (c) intraspinally and intravenously in combination. (a) When immune serum is given intraspinally the agglutinins are very much diminished after 8 hours and practically disappear at 12 hours. They appear in the blood at the 4th hour after injection and quickly diminish. (b) After intravenous injection of immune serum, when the meninges are inflamed, agglutinins appear in the spinal fluid in small amounts in about 12 hours and increase to the 25th hour. More than one-half of the agglutinins disappear from the blood within 8 hours and remain in low concentration at 25 hours. (c) After combined intraspinal and intravenous injection the agglutinins remain in higher concentration in the spinal fluid and for a longer time than by method (a) or (b). The curve descends after 12 hours, and agglutinins are present at 25 hours. They remain in maximum concentration in the blood for 25 hours.


1931 ◽  
Vol 54 (6) ◽  
pp. 859-873 ◽  
Author(s):  
S. T. Walton

These experiments show: 1. That the surface tension of normal blood serum is considerably lowered by standing undisturbed for a period of 1 hour (time-drop). 2. That the greatest time-drop recorded is with serum diluted approximately 10,000 times in fresh serum, and 50,000 times in heated serum. 3. That immune serum is not affected in the same manner by heat as is normal serum. Syphilitic serum and anti-sheep cell rabbit serum behave similarly in this respect. 4. That serum albumin is much more readily soluble in alkaline buffer solutions than globulin is, and that globulin from normal serum ionizes more than that from syphilitic serum. Further investigations are being made in an effort to determine why the proteins aggregate or dissociate under the influence of the factors under consideration.


1918 ◽  
Vol 28 (1) ◽  
pp. 11-17 ◽  
Author(s):  
Simon Flexner ◽  
Harold L. Amoss

For the neutralization of the virus of poliomyelitis by antibodies, active complement is not required. In carrying out immunity tests it is imperative to choose a virus of established grade of virulence and to make adequate control observations. The neutralizing substances pass from the blood of actively immune monkeys into the cerebrospinal fluid when the permeability of the meningeal-choroidal complex is increased by an aseptic inflammation such as that induced by an intraspinal injection of horse serum. The immunity bodies in effective neutralizing quantities can be detected in the cerebrospinal fluid as early as 12 hours and as late as 48 hours after the intraspinal injection of horse serum. Doubtless the passage continues as long as the inflammation persists. This ability of the neutralizing substances to pass from the blood into the cerebrospinal fluid under conditions of inflammation doubtless plays an important part in arresting the multiplication of the virus on which the cessation and restoration of the poliomyelitic processes depend. The widespread involvement in the inflammatory conditions of the meninges, choroid plexus, and substance of the nervous organs, accompanied by severe lesions of the blood vessels in the last structures especially, opens the way widely for the passage of antibodies into the cerebrospinal fluid, whence all parts of the nervous tissues are reached, and also, probably, for direct transudation into the affected parts of the spinal cord and brain. The neutralization of the virus on which the continuance of the active pathological process depends is thus readily accomplished. Under these circumstances the use of an alien specific immune serum to anticipate the action of the individual's own immunity products appears logical, while the employment of normal serum has no basis in experiment and would seem not to offer any therapeutic advantage whatever.


1920 ◽  
Vol 32 (3) ◽  
pp. 283-293 ◽  
Author(s):  
Ida W. Pritchett

1. No demonstrable antiopsonins are formed in rabbits following the intravenous injection of monovalent pneumococcus horse sera, Types I, II, and III. 2. The serum of rabbits injected with immune pneumococcus horse serum, Type I, II, or III, or with normal horse serum, when mixed in the proportion of 1:4 with Type I or Type II pneumococcus horse serum, can greatly augment, in vitro, the opsonization and agglutination of Type I and Type II pneumococci by the homologous immune horse sera. No similar effect is obtained with Type III serum and pneumococci. 3. The increase in opsonization and agglutination is dependent upon (a) specific sensitization of the pneumococci by the homologous immune serum and (b) the presence of the precipitating serum. In the absence of sensitization, as when a heterologous or normal horse serum is employed, opsonization and agglutination do not occur, even though a precipitating mixture is provided. The substitution of normal rabbit serum for the precipitating rabbit serum gives opsonization and agglutination in dilutions slightly higher than are effected with salt solution only, due possibly to the more favorable medium created for the leucocytes by the addition of 25 per cent of whole rabbit serum. 4. Different methods of combining the immune horse serum, precipitating rabbit serum, and pneumococci yield very similar results, preliminary sensitization of the bacteria before precipitation, or precipitation in the rabbit-horse serum mixture before the addition of the pneumococci for sensitization causing little if any difference in result from that obtained when immune horse serum, precipitating rabbit serum, and pneumococci are all mixed and incubated together. 5. This increased opsonization in the test-tube does not seem to be paralleled by increased protective power, or at any rate such protection is not readily demonstrated.


1929 ◽  
Vol 50 (4) ◽  
pp. 431-437 ◽  
Author(s):  
Louis Tuft ◽  
Susan Griffith Ramsdell

After the injection of normal horse serum in the human being, serum sickness occurs even more regularly than in cases treated with the various immune sera, but this is not accompanied by the production, to any notable degree, of circulating antibodies of the various types that are regularly to be demonstrated after the administration of immune serum and its resulting serum sickness. Since normal horse serum therefore appears to be weakly antigenic, and immune serum highly antigenic for the human being, one must assume that this difference is the result of some alteration in its antigenic characteristics produced during the course of the immunization or of its preparation for use; or that the specific antibody which is responsible for the phenomenon of serum sickness has not yet been identified; or that this phenomenon is not in any way dependent on the presence of the various known antibodies to normal horse serum.


1919 ◽  
Vol 30 (6) ◽  
pp. 569-587 ◽  
Author(s):  
M. A. Barber

1. Under the conditions stated pneumococci grow as readily in the serum of horses highly immunized to the homologous organism as they do in normal horse serum, and the rate of growth is not appreciably diminished. 2. This failure of immune serum to affect the growth rate is not altered when fresh rabbit blood, fresh human blood, or rabbit blister fluid is added in order to supply any hypothetical complement which might be lacking. 3. We have not been able to show that when immune horse serum is injected intravenously into rabbits or intraperitoneally into mice, it acquires the property of killing pneumococci or inhibiting their growth. 4. Experimental evidence has been obtained indicating that in the peritoneal cavity of the passively immunized mouse the growth of extracellular pneumococci continues at apparently the normal rate, until the bacteria are engulfed by phagocytes. 5. The immunizing and protective power of antipneumococcic serum probably depends, in part at least, on properties which are not at present known. It has not been possible in the present study to demonstrate that one of these properties consists in delaying the growth of pneumococci.


1938 ◽  
Vol 31 (7) ◽  
pp. 799-806 ◽  
Author(s):  
G. M. Findlay ◽  
F. O. MacCallum

Among 3,100 persons immunized against yellow fever with virus and immune serum over a period of five years, 89 cases of jaundice have been traced. The symptoms are those of a hepatitis and closely resemble those produced by common infective hepatic jaundice, cases of which have frequently been noted as occurring in the same areas. The average period between the time of inoculation and the development of hepatitis is between two and three months. Attention is directed to the occurrence of hepatitis in horses, usually two to three months after immunization against the viruses of horse sickness and equine encephalomyelitis, and also after the injection of horse serum containing antitoxins against Cl. welchii toxins. Similar symptoms were observed, though to a lesser extent, in normal horses. The only factor common to the inoculated horses and men was the injection of homologous proteins, either in sera or in tissue extracts. The only theories which at present explain the observed facts are that either (1) a hepatotoxic virus is introduced with the virus inoculum or that (2) two factors combine to induce the hepatitis ( a) a hepatotoxic substance present in the homologous sera or tissue extract injected and ( b) an infective agent which, in the case at least of human beings, is probably the causal agent of common infective hepatic jaundice.


1931 ◽  
Vol 54 (4) ◽  
pp. 623-627 ◽  
Author(s):  
Ernest G. Stillman ◽  
Arnold Branch

1. When mice are passively immunized by the intraperitoneal injection of antipneumococcus horse serum or actively by the injection of heat-killed pneumococcus cultures, and are then alcoholized and sprayed with a culture of pneumococci of the same type as that of the bacteria employed in immunization, a considerable number die with localized lesions in the lungs. 2. If instead of injecting immune serum of the type corresponding to that of the bacteria employed in producing the infection, normal horse serum or immune serum of a heterologous type be injected, or if the animals be previously immunized by the injection of killed pneumococci of a heterologous type, none of the animals which die show any evidence of localization of the infection in the lung. 3. The occurrence of pulmonary lesions in alcoholized mice after spraying with a culture of pneumococci is the consequence of a general immunity of a very mild grade.


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