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Studies the cellular localization of Salmonella Adelaide flagellin following injection into the rat in the presence of Freund's complete adjuvant. Comparison of the uptake of flagellin in the popliteal lymph nodes following its injection into the foot-pad of the rat in aqueous solution and in Freund's complete adjuvant; Antigen taken up by the reticular dendritic web of the cortical lymphoid follicles that may act as an antigen depot; Implications on experimental biology and medical science.

Studies the immune response of normal and tolerant rats to Salmonella Adelaide flagellin in Freund's complete adjuvant. Antibody production considerably enhanced if the antigen were injected in emulsion with Freund's complete adjuvant; Ability of antigen injected in Freund's complete adjuvant to be retained in the body for a considerable period of time; Implications on experimental biology and medical science.

A study has been made of the conditions under which antibody to bacteriophage is produced in the chick embryo chorio-allantoic membrane (CAM), following the direct inoculation of spleen cells from an adult fowl previously inoculated with bacteriophage. Antibody is produced in the CAM when spleen cells are transferred 48 hours after a primary in vivo antigenic stimulus, and in greater amounts following transfer 24 hours after a secondary in vivo stimulus. High titres of antibody also appear in the blood and spleen of the recipients. Cells transferred after a primary stimulus given either in vitro or by simultaneous injection of cells and antigen produced very small amounts of antibody. The transfer of spleen cells from stimulated adult fowls to genetically dissimilar recipients is accompanied by the appearance of proliferative lesions on the CAM. These are characteristic of the Simonsen phenomenon, and are a manifestation of the graft versus host reaction. When the donor and recipient are derived from the same highly inbred strains of fowls, few, if any, lesions develop. There is no macroscopic evidence for the proliferation of the donor cells, but antibody, in comparable amounts to that produced in outbred systems, appears in the recipient membranes. [ABSTRACT FROM AUTHOR]

The article presents a study according to which immunization of adult fowls with embryonic tissue does not increase the ability of their blood large lymphocytes to produce lesions on the ehorio-allantoic membrane. The results of Coombs' tests and of haemagglutination tests indicate that inoculation of spleens from 16-18 day embryos provides an antigenic stimulus in the adult fowl, but that 12-day embryonic spleens evoke no detectable immune response. The bearing of these findings on the application of the clonal selection theory of acquired immunity to the Simonsen phenomenon is discussed.

The article informs that the characteristics of aWS, a non-mouse-pathogenic mutant of the influenza virus strain WS, and its reversion to mouse virulence under certain conditions of passage in the chick embryo have been described in a recent paper. With the object of reaching a clearer understanding of the difference between aWS, and WS, investigations were made of the behavior of aWS, on intranasal inoculation into mice and of the results of recombination between aWS, and one of the mouse pathogenic revertant strains to which it gave rise.

Investigates the behavior of aWS, a mutant of the WS strain of the influenza virus, to see if the change in character were due to a complete mutation to avirulence or if it, too, could be more readily explained in terms of the suppressor gene concept. Background on the WS strain; Emergence of a new strain called avirulent WS or aWS; Limit infecting dilution passages in the allantoic cavity of the mouse lung, which aWS was taken through; Determination of mouse lung pathogenicity; Results of the limit infecting dilution titration.

A study has been made of the capacity of heat-inactivated influenza virus to contribute to recombination reactions with an appropriate active virus as the second component. Only virus which was non-infective by rigid criteria was used as the inactive partner. The following temperatures, 37°, 55°, 57-5° and 60° C. were used, the exposures being arranged so that the minimal time necessary for complete inactivation was included. With M+ as the heat-inactivated component, MEL recombinants were obtained in each case with the material having received minimal exposure. None of the M+ material given 18-20 hours before adding WS--(active) showed any significant interference. Using M+ inactivated at 37° C. the yield of recombinants was almost unrelated to the size of the dose of inactivated virus inoculated 18-20 hours previously. With WS-- as the inactivated component and M+ as the active one, there was very little production of WSE recombinants, a total of three strains being obtained, all from systems containing virus inactivated at 37° C. However, WS--, inactivated at 37° C. and Administered 18 hours before M+, strongly interfered with growth of the M+. In a single experiment in which M+ which had not been completed inactivated was used with active WS--, an unusual heat labile variant of M+ was obtained. [ABSTRACT FROM AUTHOR]

Ribonuclease is capable of inhibiting the production of haemagglutinin in de-embryonated eggs infected with influenza viruses. The inhibitory effect is increased (a) if time is allowed for penetration of ribonuclease before the virus is added, (b) if Ca++ is eliminated from the saline medium used, and (c) if the DEE are chilled before adding virus. Ribonuclease greatly reduces the subsequent yield of haemagglutinin both in the fluid and in the chorio-allantoic membrane if added after virus production is in full progress. When a suitable mixed inoculum is used, the degree of double neutralization (phenotypic mixing) shown by the harvested virus is reduced if ribonuclease has been used. No evidence of any increase in incomplete virus was obtained. The inhibitory effect of ribonuclease persists for at least 96 hours if the de-embryonated egg is held at 0° C. but is lost in 48 hours at 37° C. There are only minor differences in the susceptibility of different virus strains to inhibition by ribonuclease. The content of soluble complement fixing antigen in the chorio-allantoic membrane is reduced, but to a much smaller extent than the haemagglutinin content. [ABSTRACT FROM AUTHOR]

Interpolation of a period of chilling at 0° C. for 20 hours at any stage of the process makes very little difference in the sequence of influenza virus production at 37° C. in the de-embryonated egg. Double infections with the strains M+ and WS-- which interact to give doubly neutralized virus (phenotypic mixtures) and an easily isolated recombinant can provide information, based on the dominance of one strain over the other, about the early stages of infection which cannot be obtained from single infections. When one virus is taken up by the cells in the cold before the other virus is added also in the cold, the virus presented second dominates in the yield. This dominance is annulled or reversed when the cells are pretreated with RDE. When preparations on which one virus has been adsorbed in the cold are exposed to 37° C. before addition of the second virus, the first virus dominates the eventual yield if the intervening period is more than 10 to 30 minutes. These indications of two initial stages in the process of infection are discussed in relation to the work of Ishida and Ackermann (1956). [ABSTRACT FROM AUTHOR]

A mutant, M+d, of the influenza strain M+ is described, which differs from the parent M+ in its heat resistance and indicator status and which has lost all virulence for both the chick embryo and the mouse lung. In addition, it lacks the enzymic activity of M+ and occupies a different position in the fowl cell receptor gradient. M+d can readily be maintained by allantoic passage at limit infecting dilution. However, passage at low dilution (10-2) or in the de-embryonated egg reveals a high rate of reversion to the M+ parental type with restoration of all M+ characters. It is especially noteworthy that the full virulence for both mouse lung and chick embryos is regained along with the in vitro characters. The reversion of M+d to M+ occurs as readily with tenth limit dilution passage material as with the original isolate. Since it must be postulated that the reversion from M+d to M+ represents a unitary genetic change, despite the large number of changed characters, the presence of a modifier or suppressor gene is suggested and some of its implications discussed. [ABSTRACT FROM AUTHOR]

Presents the results of a study comparing the behavior of different virulence markers in recombinations. Characteristics of the virulence markers; Consistency of the neuropathogenicity of the strain NWSE and the NWS strain; Information on the independent segregation of the four linkage groups.

An analysis has been made of the progeny resulting from recombination between the influenza virus strains MEL and NWSE with special reference to heterozygosity. With this system most of the recombinants obtained showed no evidence that they were derived from heterozygotes. A limit dilution fluid showing both heterozygosity and a large proportion of doubly neutralizable virus was further analysed along the same lines. It yielded all four of the possible combinations of "linkage groups". The results are discussed and the conclusion reached that there must be some means by which potential heterozygotes can give rise to progeny of homogeneous serological character. [ABSTRACT FROM AUTHOR]

Recombination experiments were carried out between the influenza type A strain WSE, and other type A influenza strains Swine 15, SR-CAM, Ocean Island, CHO and A/Persian Gulf/2/52. Recombinant virus strains which had acquired various characteristics of WSE, notably convertibility to the indicator state and pathogenicity for chick embryos and for mouse lung, while retaining the serological type of the other parent strain, were isolated in all experiments except those with Ocean Island virus. The yield of recombinants in all cases was lower than in previously described experiments and a selective medium was usually needed for their isolation. The extent to which chick embryo and mouse lung pathogenicity were expressed in the recombinant strains varied from one set of experiments to another and also between individual recombinant clones derived from a single experiment. These pathogenic activities tended to find weaker expression in the recombinants with the type A strains of more recent origin such as CHO (1950) and Persian Gulf (1952). This weak pathogenicity could be enhanced by appropriate passage. [ABSTRACT FROM AUTHOR]

Recombination between the A prime strain CAM and the influenza A strain WSE gave rise to the forms CAM+ and WS -- corresponding to an interchange of characters formulated as A'bD-FCE+abd-fce→ A'bD-fee and abd-FCE. A very small yield only of recombinants was obtained. Back recombination, according to the scheme A'bD-fce+abd-FCE→ abdfce+A'bDFCE, occurred readily, giving a high yield of both original forms. A variety of WS derivatives showing varying degrees of loss of virulence for the mouse lung and/or the chick embryo were obtained in these interactions. [ABSTRACT FROM AUTHOR]

With repeated passage of influenza virus WS -- in deembryonated eggs using large inocula, highly incomplete virus develops and passage fails after 4-7 transfers. Experiments to determine the first cycle haemagglutinin yield from a graded series of inoeula have been made with virus of different degrees of incompleteness. The results show that many virus preparations have a much greater power to produce first cycle haemagglutinin than to give conventional evidence of infectivity. Evidence that this is not due to multiplicity reactivation is provided by comparison with heated material in which multiplicity reactivation probably does occur. Incomplete virus can contribute genetic characters to recombinants produced from double infection with an appropriate active virus. [ABSTRACT FROM AUTHOR]

Two modified lines of the influenza A prime virus, CAM, were developed: (1) CAM-SR resistant to anti-CAM serum, and (2) CAM-MP fully adapted to growth in the mouse lung. A study was made of the distribution of mouse lung pathogenicity among pure clone samples of the CAM-MP strain at different stages in the course of its adaptation to mice. Recombination experiments between CAM-MP and CAM-SR yielded only one mouse pathogenic CAM-SR strain, and gave CAM-MP strains which showed a wide variation in their power to produce mouse lung lesions. Few of these latter strains had the lesion producing power of the standard CAM-MP strain. [ABSTRACT FROM AUTHOR]

A re-examination has been made of recombinations in which neuropathogenicity for mice has been concerned. Using the symbols previously adopted with the addition of g for neuropathogenicity, and G for its absence, the following interactions have been observed: ABDF-ceg/abdf-CEG → abdf-ceg aB'df-cEg /abdf-ceG → abdf-ceg abdf-cEG aB'df-cEG aB'df-cEG/ab'(d)f-(c)eg → ab'(d)f-(c) eG ab'(d)f-(c) EG There was a wide variation in the degree of neuropathogenicity shown by the recombinants. Many experiments showed a proportion of non-lethal strains, and there was a general tendency for the average degree of neuropathogenicity to diminish on continued limit dilution passage. [ABSTRACT FROM AUTHOR]

A modified technique for de-embryonation of fertile eggs is described which allows retention of the whole surface of the allantois for influenza virus growth. With the standard technique involving treatment of the cells with receptor destroying enzyme RDE, haemagglutinin and newly produced infective virus are liberated earlier than in the normal allantoic cavity. Recombination in the first infective cycle is only demonstrable if the dose of virus used is sufficient to ensure that a considerable proportion of cells will be infected with at least two virus particles. When the interval between the addition of the two viruses to the system is one hour or less, recombination can be demonstrated. It is not shown when the interval is two hours. With cells all initially infected and treated with RDE to minimize the likelihood of reinfection, virus liberation continues for a long period. The constitution of the virus liberated into the fluid at different periods is almost uniform in regard to the extent of anomalous neutralization, the relative apparent excess of one virus over the other, the degree of "incompleteness" of the virus and the types of virus isolated by allantoic inoculation at limiting infective dilutions. The ratio of the recombinants MEL and AVSE from M +/WS -- experiments is approximately 4-7:1. Discussion of the significance of this ratio in the light of the existence of double neutralization leads to the conclusion that the viruses concerned normally have a diploid constitution. [ABSTRACT FROM AUTHOR]

In the recombination systems MEL/WSE or M +/WS -- heat inactivation of one component (56° 0. for 30 minutes) does not prevent the appearance of recombinants of the same serological type as the heated component. With only very minor exceptions, all the results obtained are compatible with the hypothesis that the genetic material of the viruses is distributed in the form of two linkage groups. [ABSTRACT FROM AUTHOR]

The strains M+ and WS- obtained as recombinants from MEL and WSE strains of influenza A virus in previously reported experiments, have been used in back-recombination experiments to produce MEL and WSE. Several strains of each type have been obtained as well as a number of anomalous strains whose nature is discussed in the text. Irrespective of the way the experiment is carried out, MEL plus WSE or M+ plus WS-, the order of abundance of the four products in technically satisfactory experiments is MEL WS- M+ WSE. Preliminary evidence for the existence of " heterozygotes" is presented. [ABSTRACT FROM AUTHOR]

There is a close relationship between the haemagglutinin, the cell sensitizing agent and the complement fixing antigen in mumps allantoic fluid. These three activities appear to be properties of the virus particles themselves. Mumps virus agglutinates human as well as fowl cells, but there appears to be a much weaker adsorption of virus particles to human cell receptors than to fowl cell receptors. There is evidence that mumps virus is present in infected embryonic fluids in an aggregated state. Cells sensitized with mumps virus have the capacity to agglutinate normal cells. The mechanisms of haemagglutination, cell sensitization, agglutination of sensitized cells by immune serum and agglutination of normal cells by sensitized cells are discussed. There is close resemblance between the behaviour of mumps virus and that of Newcastle disease virus. [ABSTRACT FROM AUTHOR]

Although it was not possible to obtain consistent yields of high-titre mumps allantoic fluid, sufficient high-titre fluid for production of mumps vaccine on a laboratory scale was obtained by allantoic inoculation of high-titre seed virus into eight-day chick embryos and harvesting the allantoic fluid after four days' incubation at 35° C. Mumps vaccine was prepared by an addition of 0·1 p.c. formalin to the infected allantoic fluid which was then held at 37° C. for twelve hours. 0·25 p.c. phenol was added just prior to use. The keeping quality of different batches of vaccine varied considerably, but antigenicity seemed to be little affected by loss of haemagglutinating activity. All strains of mumps virus used in vaccine preparation were serologically similar, although one strain END did not appear to be identical with the others. Two doses of 2 ml. vaccine each were given subcutaneously, with an interval of three weeks between doses, to two groups of children. In general it was found that the higher the pre-vaccination antibody the greater the response to the first injection. In neither group was there any clear response to the second inoculation. [ABSTRACT FROM AUTHOR]

A survey has been made of the titres of "T" agglutinins in human sera from individuals of various ages. There is no "T" agglutinin in umbilical cord serum, the agent develops normally during the first year of life and after the age of three the titres are not significantly different from those of adults. Sera from cases of atypical pneumonia with cold agglutinins are significantly higher in "T" agglutinins than normal sera. "T" agglutinins and cold agglutinins in these sera are distinct. There is no significant alteration in the "T" agglutinin titre of sera from cases of mumps, influenza, psittacosis and hepatitis. [ABSTRACT FROM AUTHOR]

Three strains of mumps virus have been isolated in chick embryos from human saliva and passaged 15 to 30 times. The virus multiplies readily after yolk sac or amniotic inoculation and some-what less readily after allantoic inoculation. [ABSTRACT FROM AUTHOR]