Valerie E. Jones

Reaginic antibodies and immunity to Nippostrongylus brasiliensis in the rat

Rats thymectomized at birth were infected with Nippostrongylus brasiliensis at 6 weeks of age. In some, but not all, rats egg production was greatly prolonged after the primary infection. Thymectomized rats were less resistant than controls to second infections. In rats infected at birth the development of resistance was significantly delayed. Neonatally infected rats, when they were 6 weeks old, were less resistant to reinfection than adult controls. Rats infected three times in the neonatal period were more resistant to challenge at 6 weeks of age than rats infected once at birth, but less resistant than adult controls. The degree of immunity induced by a single neonatal infection was variable; some rats showed little or no resistance to reinfection 6 weeks later. Antibody formation, measured by the occurrence of reagins, was altered in the same way by both neonatal thymectomy and neonatal infection. In the thymectomized (immunologically deficient) and newborn (immunologically immature) rats, reagin formation following initial infection was delayed; there was a reduced anamnestic response after challenge; mean titres were lower and more variable than in control animals; and in some rats circulating reagins were never detected. In thymectomized rats the capacity to demonstrate anaphylaxis was as variable as in control rats, but in the few thymectomized rats in which egg production was prolonged, anaphylaxis was slight at a time when most intact rats had developed the capacity to show anaphylaxis. Rats infected at birth and adult rats infected at the same time were equally susceptible to systemic anaphylaxis 6 weeks later, although by this time there was a marked difference in the degree of resistance to the parasite developed by the two groups. In adult rats splenectomy before, during or after initial infection had no effect either on the rate of development, or the degree of immunity induced by primary or secondary infections, or on antibody formation. We would like to thank Miss W. Griffiths and A. J. Edwards for their willing technical assistance. This work was done whilst one of us (B.M.O.) was the holder of a Wellcome Fellowship of the Animal Health Trust.

Passive protection with cells or antiserum against Nippostrongylus brasiliensis in the rat

Rats can be passively protected against N. brasiliensis either with antiserum or with cells. Only some pools of antiserum (15 of 48 pools) and a few batches of cells (three of 11 batches) were protective. Protective activity was found in serum taken after one infection as frequently as after several infections and gave the same degree of protection. This suggests that second and subsequent infections do not stimulate an anamnestic increase in protective antibodies in the circulation. Serum and cells taken from the same rats were unrelated in their protective capacity; sometimes serum protected when the cells were ineffective and the reverse also occurred. Cells transferred from the spleen, peritoneal cavity or mesenteric lymph nodes were capable of initiating reagin formation, irrespective of their ability to protect against N. brasiliensis . When protection was achieved with transferred cells, the parasite life-cycle was shortened by only 1–2 days. We have found no evidence that a delayed mechanism of the homograft type is concerned in immunity to N. brasiliensis in the rat. We thank Miss W. D. Griffiths and Mr A. J. Edwards for their willing assistance. The statistical analysis was kindly done for us by Miss M. V. Mussett of the Statistics Department at our Institute.

Reaginic Antibodies and Immunity to Nippostrongylus brasiliensis in the Rat

1. Passive transfer of immunity to Nippostrongylus brasiliensis with pooled antiserum from immune rats was neutralized in vivo by intravenous injection of small amounts of a saline extract of adult worms. This inhibition of protection was associated with systemic anaphylaxis and appeared to result from the neutralization of protective antibodies. 2. Serum from infected rats was fractionated by G-200 Sephadex gel-filtration. Reaginic antibodies were shown to be intermediate in molecular size between 7S and 19S globulins in sera from both singly and multiply infected animals. In immunoelectrophoresis they migrated with fast immunoglobulins but could not be related to either IgG or IgA rat immunoglobulins. The same serum fractions gave both homologous passive cutaneous anaphylaxis (PCA) and systemic anaphylaxis. 3. Blocking antibodies were found both in the 7S and 19S fractions after separation on G-200 Sephadex. These antibodies were found in sera from rats immunized with worm extracts as well as in sera from singly and multiply infected animals. 4. The saline extract of adult worms was fractionated on G-200 Sephadex. The isolated antigenic material (allergen) for both homologous PCA and systemic anaphylaxis seemed to be a protein with a molecular weight of approximately 12,000–17,000.