Immunized Dams Research Articles

The astrocyte is a target cell in mice persistently infected with mouse hepatitis virus, strain JHM

Mouse hepatitis virus, strain JHM (MHV-JHM), causes a late onset, clinically apparent, demyelinating encephalomyelitis in 40% of suckling C57BL/6 mice born to immunized dams. Suckling mice born to unimmunized dams rapidly succumb to an acute encephalomyelitis. MHV-JHM can be isolated from the brains and spinal cords of maternal antibody-protected mice when the late onset disease becomes clinically apparent, showing that the virus must be present in these mice when they are still asymptomatic. To determine which cells of the central nervous system (CNS) were potential reservoirs for the virus during the asymptomatic period, tissue sections were assayed simultaneously by immunoperoxidase and immunofluorescence staining for the presence of viral antigen and for glial fibrillary acidic protein (GFAP), a marker for astrocytes. 2 The results indicate that 20% (range 0–52%) of the MHV-JHM infected cells in asymptomatic mice were astrocytes. In mice symptomatic with late onset hindlimb paralysis, a higher percentage of infected cells were astrocytes. These results indicate that astrocytes are a target cell in both symptomatic and asymptomatic mice persistently infected with MHV-JHM, and suggest that the astrocyte is a potential cellular reservoir for MHV-JHM in asymptomatic mice.

Fetal and maternal immunologic manifestations of intrauterine adenovirus SV-20 infection

Rhesus monkey fetuses of either immune or nonimmune dams were inoculated in utero with Adenovirus SV-20 (AdSV-20), a virus capable of inducing fetal pneumonia, and studied immunologically at various intervals. AdSV-20 infection at 90–100 days gestational age resulted in absolute lymphopenia in a few fetuses, reduced numbers of peripheral blood lymphocytes (PBL) which formed rosettes with sheep erythrocytes (ERL) and reduced complement-receptor lymphocytes (CRL) in a majority, while Fc fragment-receptor lymphocytes (FcRL) were occasionally increased. There was a tendency for depression of ERL and CRL early in infection of 120–130-day fetuses, followed by stimulation of these populations and FcRL in later phases. Maternal immunity did not protect against these effects of AdSV-20 infection in fetuses. Immune and nonimmune dams were spared adverse clinical effects and had no changes in lymphoid cell populations following inoculation of their fetuses. Despite precocious production of circulating IgM, fetuses of nonimmune dams had little or no demonstrable anti-AdSV-20 serum neutralizing (SN) antibody, indicating that the ability to develop an effective immune response was suppressed or had not been acquired at the gestational ages studied. Nonimmune dams displayed little evidence of seroconversion following inoculation of their fetuses with AdSV-20, except in those dams whose fetuses died in utero, whereby there was a significant antibody response. SN antibody titers of immune dams were not boostered substantially subsequent to inoculation of their fetuses, and fetal SN titers were lower than maternal titers, suggesting absence of an active fetal antibody response in this group also. Direct inoculation of AdSV-20 into 90–130-day rhesus monkey fetuses provided a model system for immunologic study of fetal infection, probably involving complex fetal-maternal interactions, in a situation where the infected, viable fetus and its dam appeared to be microbiologically isolated from one another.

Immunization of swine with heat-stable Escherichia coli enterotoxin coupled to a carrier protein does not protect suckling pigs against an Escherichia coli strain that produces heat-stable enterotoxin.

Pregnant swine were immunized parenterally with purified heat-stable Escherichia coli enterotoxin that was made antigenic by coupling it to bovine immunoglobulin G. Immunized swine had high titers of antitoxin in serum and colostrum as measured by radioimmunoassay. However, the heat-stable enterotoxin neutralizing titers of the serum and colostrum from immunized swine were comparatively low. Newborn pigs suckling their immunized dams were not protected against challenge with porcine enterotoxigenic E. coli that produce heat-stable toxin but do not produce heat-labile toxin.

Vaccination Against Infectious Bronchitis and the Immunosuppressive Effects of Infectious Bursal Disease

An immunosuppressive effect was demonstrated in chickens which were infected with infectious bursal disease virus (IBDV) early in life and prior to or shortly after vaccination with infectious bronchitis virus (IBV). This effect was evident by an increased susceptibility to respiratory tract infection with IBV and reduced virus-serum neutralizing antibody levels. Chickens which were hatched from dams susceptible to infectious bursal disease (IBD) were less responsive to IBV immunization attempts, if exposed to IBDV, than were those individuals hatched from IBD immune dams. However, in some cases, chickens from IBD immune dams were also more susceptible to IBV challenge when they had been exposed to IBDV and when compared to birds unexposed to IBDV but vaccinated against IB. An effect of cyclophosphamide on the bursa of Fabricius also had an immunosuppressive action on IBV immunity which was similar to the results from IBDV exposure. The data engendered from these trials may explain the unsatisfactory immunity sometimes observed under field conditions when broilers and replacement pullets are vaccinated at an early age.

Experimental neonatal colibacillosis in cows: immunoglobin classes involved in protection.

Pregnant cows were vaccinated with one of four vaccine preparations to induce passive immunity in their offspring against a homologous oral challenge with Escherichia coli strain B-44. Quantitative assays of specific antibody in colostral whey from both immunized and nonimmunized dams revealed that immunoglobulin G, immunoglobulin A (IgA), and immunoglobulin M (IgM) with anti-O (somatic) activity were present in whey of all dams tested, whereas a marked deficiency of IgA and IgM anti-K immunoglobulin was noted in the whey from control dams only. The degree of scours (neonatal colibacillosis) induced by oral challenge was evaluated clinically and reported by a semiquantitative scour index as 0 to 4+. Calf scour indexes showed an inverse relationship to the frequency of occurrence and to the levels of IgA and IgM in whey of dams vaccinated with killed vaccine, live vaccine, and culture supernatant, and from nonvaccinated controls. The data strongly suggested that IgA and colostral IgM anti-K immunoglobulins were important in passive immunity in experimental neonatal bovine colibacillosis.

The susceptibility of young and newborn calves to bovine ephemeral fever virus.

The pathogenicity of a field strain, 417, of bovine ephemeral fever (BEF) virus for newborn and young calves was investigated. Three colostrum-deprived newborn calves inoculated intravenously developed severe clinical disease and viraemia, and produced long-lasting neutralising antibody. The incubation period in these animals was 10 and 11 days, compared with 5 to 7 days for older calves. Two newborn calves which received colostrum from immune dams and 2 which received colostrum from non-immune dams failed to respond clinically to intravenous inoculation with strain 417. The neutralising antibody response of these calves was of short duration. Four calves, 7 to 8 weeks old and lacking detectable neutralising antibody to BEF virus, or having low levels of antibody, did not develop clinical disease when inoculated intravenously. Four calves 12 to 14 weeks of age and free of detectable neutralising antibody to BEF virus developed clinical disease when inoculated with strain 417.

Experimental studies on the bridging hypothesis of anaphylaxis: haptenic determinants required to elicit immediate-type reactions in calf skin by separate or concurrent sensitization with reagins of different specificity.

The present study has established, that cows suitably immunized with either DNP-edestin (DNP-Ed), di-DNP-gramicidin-J [(DNP)(2)-Gram], respectively, or p-azobenzenearsonate-Ed (ABA-Ed) synthesized and secreted reaginic antibodies (IgE) into colostrum. Whereas ABA-Ed failed to elicit more than a low response, there was however a persistent and increased antibody synthesis between 10 and 56 days after priming with DNP-Ed. Bivalent and multivalent DNP haptens differing in molecular size, degree of substitution, and rigidity were compared for their effectiveness in eliciting Prausnitz-Küstner (P-K) reactions in either newborn colostrum-deprived calves or in those 4 wk of age. The sensitization with reaginic anti-DNP antibody has been accomplished either by feeding colostrum of the immunized dam or by intradermal injection of reaginic serum or colostral whey. It could be demonstrated that equimolar doses of the bivalent alpha,N-(epsilon,N-DNP-aminocaproyl-)-epsilon,N-DNP-L-lysine and the multivalent dinitrophenylated bovine serum albumin were equally effective in eliciting reactions in skin sites provided that a high affinity antibody was used for sensitization. By contrast, the comparatively rigid, bivalent hapten, (DNP)(2)-Gram consistently failed to induce comparable reactions. Furthermore, it was clearly shown that optimal distances of determinant groups on the haptenic molecule are a prerequisite for positive P-K reactions, since alpha,epsilon,N-bis-DNP-lysine failed to induce comparable reactions. Concurrent sensitization of skin sites with reaginic anti-DNP and anti-ABA antibodies provides the final proof that cross-linking of two adjacent reaginic molecules on the mast cell surface by a bivalent hapten is required for effective elicitation of immediate-type reactions. This has been accomplished by utilizing the bivalent epsilon,N-DNP-alpha,N-[(4-hydroxy-3-azobenzenearsonic acid)-phenacetyl]-L-lysine (DNP-ABA) carrying noncross-reactive haptenic groups, which was consistently effective in eliciting P-K reactions in doubly but never in singly sensitized skin sites. It is apparent from the results that equimolar doses of monovalent haptens could completely inhibit the response to DNP-ABA. The present studies finally establish that mast cells of newborn colostrum-deprived calves lack IgE molecules on their surface. Thus, mast cells of newborn calves may be unique, to investigate the molecular mechanisms involved in immediate-type reactions more precisely.

Antibody and resistance to infection with Yersinia pestis in the progeny of immunized rats.

The presence of HA antibody to the Fraction I antigen of Yersinia pestis was examined in sera of neonatal, suckling, and newly weaned Rattus norvegicus. Newborn rats from immunized dams possessed antibody at birth, before suckling. Antibody declined or disappeared in suckling rats nursed by unimmunized dams, while antibody appeared in sera of rats born of unimmunized dams and fostered by immunized dams. Antibody also appeared in suckling young of dams inoculated with antiserum to Y. pestis prepared in rabbits. Offspring of immunized dams usually had titers of HA antibody at weaning equal to 25%-50% of the dams' titers. Most one-week-old rats and many six-week-old rats that had been nursed by immunized dams survived inoculation with about 1,000 virulent plague bacilli, and all young rats that possessed HA antibody titers of > 64 at the time of inoculation survived. The significance of passively acquired antibody and protection in the epidemiology and the ecology of plague was considered.

Induction of the feline oncornavirus associated cell membrane antigen in human cells.

USING indirect immunofluorescence we recently demonstrated a feline oncornavirus associated cell membrane antigen (FOCMA) in cultured feline lymphoma cells that produce feline leukaemia virus (FeLV)1,2. Using electron microscopy and ferritin-labelled immunoglobulin, Oshiro et al. obtained similar results3. We found that cats with regressing feline sarcoma virus (FeSV)-induced tumours had high titres of FOCMA-specific antibody1 and that the presence of antibody in neonatal kittens was associated with resistance to tumour development2. In the latter case, the antibody was apparently passively obtained from immune dams.

Histopathologic Differentiation of Diseases of the Nervous System of the Domestic Fowl (Gallus gallus)

5. Hwang, J., L. A. Devenpeck, and E. Dougherty. Incidence on commercial farms of duck virus hepatitis in white Pekin ducklings hatched from immunized and unimmunized dams. Avian Dis. 7:411-416. 1963. 6. Rispens, B. H. Some aspects of control of infectious hepatitis in ducklings. Avian Dis. 13:417-426. 1969. 7. Toth, T. E. Studies of an agent causing mortality among ducklings immune to duck virus hepatitis. Avian Dis. 13:834-846. 1969.

Detection of homocytotropic antibody associated with a unique immunoglobulin class in the bovine species.

AbstractHomocytotropic antibodies capable of sensitizing calf skin were demonstrated in serum of cows as early as 7 to 9 days following antigenic stimulation with rabbit serum albumin. In addition, the antibody was present in colostrum of the immunized dam and was taken up by the intestine of the newborn calf as an intact molecule. Skin‐sensitizing activity was also detected in calf urine after uptake of colostrum. Evidence is presented for an anamnestic response, suggesting the existence of an immunological memory for the formation of skin‐sensitizing antibodies. The homocytotropic antibody was shown to be heat labile and sensitive to treatment with 2‐mercaptoethanol. Time course studies revealed that homocytotropic antibodies persist in calf skin for at least 8 weeks.The immunoglobulin class associated with homocytotropic activity was enriched from appropriate antisera by salt precipitation, DEAE‐cellulose chromatography and gel filtration on Sephadex G‐200 columns. The final preparation was still capable of sensitizing calf skin for positive PCA reactions using a minimum dose of 0.009 μg N. The homocytotropic activity of the vinal fraction could not be removed by antibodies specific for the IgG class, but was completely blocked by antibodies against the fraction enriched in homocytotropic activity. The immunoglobulin class associated with skin‐sensitizing activity possesses antigenic determinants which are lacking in μ‐, α‐, and γ‐chains. The results indicate that the homocytotropic activity in the bovine species is associated with a unique immunoglobulin class analogous to human IgE.

Infectivity of Infectious Bursal Disease Virus for Embryonating Eggs

THE disease that Cosgrove (1962) reported as avian nephrosis has since been referred to as infectious bursal disease. Early attempts to propagate the infectious bursal disease virus (IBDV) by serial passage in embryonating eggs frequently resulted in failure to maintain the virus. Landgraf et al. (1967) reported a typical experience that has been observed by other workers. Infective tissue suspensions killed all inoculated embryos on first passage. Materials from embryos of the first passage killed 30% of those inoculated on the second passage, and on the third passage there was no embryo mortality.In some of the initial studies with IBDV it was observed that eggs from certain supply flocks would not support the growth of the virus, suggesting that parental antibodies from immune dams may have inhibited the virus. However, this did not provide the full explanation for failures to maintain the virus since serial passage failed even when.

Transference of maternal passive immunity to vaccinia virus in mice.

ADULT mice are highly resistant to experimental vaccinial infection, but suckling mice succumb to relatively low doses of virus introduced into the inter-scapular fat pad1. Transfer of protective antibody from immunized dams to their offspring has been described in this species for the viruses of variola2, herpes3, foot and mouth disease4 and Friend leukaemia5. In this communication, I report the transfer of antivaccinial immunity from actively immunized pregnant mice to their young. The Porton strain of albino mice and the WR strain of vaccinia virus were used throughout. The biological characteristics and method of assay of WR vaccinia virus are recorded by Turner6. A single batch of virus (titre 2 × 107 plaque forming units (P.F.U.)/ml.) was used, collected from chick embryo fibroblasts and stored in small volumes at −70° C.

Newer Knowledge About Dogs

Summary Infectious canine hepatitis antibodies are passed from an immune dam to her puppies primarily in the colostrum. This passively‐transmitted antibody declines in the puppy at a seemingly regular rate. Under the conditions of this experiment, when the antibody titer of the puppy falls below 10‐2 (1:100), that puppy can be successfully immunized. Puppies of infectious hepatitis immune dams reached this point between five and seven weeks of age. Dogs successfully vaccinated against ICH with a modified live virus vaccine shed the modified virus in sufficient concentration to immunize contact controls. This secondary immunization is apparently dependent upon the closeness of contact, and is not a reliable means of immunization. Dogs successfully vaccinated against ICH with modified live virus vaccine maintained a high antibody titer against the disease for 2 1/2 years under the conditions of the experiment.

Hemolytic Disease in Newborn Dogs

Abstract1. Bitches with erythrocytes lacking the canine A factor were immunized with intravenous injections of A-positive dog cells and mated with A-positive sires. ll A-positive pups born to such dams developed hemolytic disease provided they suckled the immunized dam during the first day of life. There was no evidence of transplacental isoimmunization or of transfer of antibody across the placenta from mother to pup. Anti-A could not be demonstrated in the blood of pups at birth and was not acquired by pups that first suckled an immunized bitch after the first day of life. A-positive pups born to a non-immunized bitch developed hemolytic disease after suckling an immunized foster dam on the day of birth.2. Of 24 affected A-positive pups, 3 were sacrificed, 9 died within three days of birth and 12 recovered, 2 with the aid of transfusions of A-negative blood. Autopsies revealed varying degrees of hepatomegaly, splenomegaly, erythroid hyperplasia of the bone marrow, extra-medullary erythropoiesis, and questionable evidence of specific injury of the nerve cells of the basal nuclei of the brain.3. The degree of anemia in the A-positive pups varied widely, the minimum hematocrit for the group being 10 per cent at forty-eight hours after birth. Erythroblastosis, reticulocytosis and spherocytosis were noted in most of the severely affected pups and osmotic fragility of the red cells was substantially increased in all of the A-positive pups exposed to anti-A.4. The concentration of bilirubin in the serum of most of the affected pups was only slightly increased. The relatively small increases in serum bilirubin, compared with those in hemolytic disease of human infants, are presumably attributable to the unusual capacity of the dog liver for excreting bilirubin.5. The red cells of all affected A-positive pups gave antiglobulin (Coombs) reactions and in surviving pups the cells were agglutinable in antiglobulin rabbit serum for as long as twenty-two days in A pups and sixty-five days in A' pups. The degree of reactivity with antiglobulin serum was not correlated with the severity of the hemolytic process. Erythrocytes of the very mildly affected A' pups were strongly agglutinated by antiglobulin serum but showed no definite sphering and only slight increase in osmotic fragility.6. Serum of the 20 A-negative litter mates examined in this study contained anti-A for periods as long as thirty-two days while the red cells of these pups remained normal. A few of the A-positive pups also had anti-A in the serum. The in vitro behavior of anti-A in the pups' sera was identical with that of anti-A in the maternal sera.7. Twelve C-positive pups in 2 litters born to bitches immunized against the canine C factor showed no evidence of hemolytic disease.8. Hemolytic disease of newborn dogs is compared with that of human infants and the need for further investigation of certain aspects of the disorder in both species is stressed.