Ellen E. E. Jarrett

Selective suppression of IgE antibody responsiveness by maternal influence

IMMUNOGLOBULIN E antibodies are produced in two circumstances: by all normal animals in infections with helminth parasites1,2, and by certain individuals against common environmental substances3. In these latter ‘atopic’ individuals, immediate hypersensitivity reactions mediated by IgE are responsible for various disorders, which in man include hay fever, allergic asthma and allergies to foods and drugs. It is known that the antibody response of the young animal may be reduced or enhanced by maternal immunisation4–9. We have examined the antibody response of rats immunised with egg albumin (EA) and show here that both these effects can occur together: suppression of the IgE antibody response may occur against a background of enhanced total antibody responsiveness in the offspring of immunised mothers.

Mucosal mast cells in vivo and in vitro.

There has recently been a flurry on the mast cell front caused, not least, by the publication of articles about the IL3-induced growth of mast cells in vitro from haemopoietic tissue. This has left bystanders, and one suspects not a few participants, confused about some of the issues involved. The reason for the confusion lies in the participation of disparate specialities - such as experimental haematology and immunoparasitology - among which communication has not been traditional: however, the revelations raise specific questions which demand an interdisciplinary approach. Thus the evidence is strong that the mast cells derived from cultured haemopoietic tissues are of a special type hitherto called atypical, intestinal or mucosal mast cells (MMC) which are known to occur in profusion in mucous membranes of helminth-infected animals. In this article Ellen Jarrett and David Haig link information about these cells obtained from both in-vivo and in-vitro experiments.

Immunological unresponsiveness to helminth parasites: I. The pattern of Nippostrongylus brasiliensis infection in young rats

Abstract The pattern of primary N. brasiliensis infections of different sizes is followed in young rats. When the number of worms that becomes established from the infecting dose is about 250 or less, worm expulsion as seen in adult rats does not occur. If considerably more than 250 worms are established, worm expulsion occurs, but is incomplete in comparison with that of adults in that it starts later, proceeds at a slower rate, and terminates when the worm population falls to a mean of approximately 200. These worm infections then persist until well into the adult life-of the rat. Attempts were made to interpret these facts in the light of published information on unresponsiveness and the self-cure reaction.

A Radioimmunoassay for Evaluation of the IgE and IgG Antibody Responses in the Rat

An assay, the paper radioallergosorbent test (PRAST), tor the measurement of specific serum IgE antibody in the rat is described in detail. This assay has been used, in conjunction with a modified PRAST for the determination of relative specific serum IgG antibody and the PRIST assay for total serum IgE [13], to measure specific IgE and IgG and total IgE immune responses in normal parasite infected rats immunized using various protocols. The results indicate that there is a relationship between the basic IgE level and the immune response, i.e. a rat strain with a low constitutive IgE level demonstrates a weak response whereas a high level strain reacts strongly. When PRAST and passive cutaneous anaphylaxis (PCA) were compared, using standardized IgE antibody containing sera, the results were in good agreement. However. PRAST is the preferable assay as it shows less intrinsic variation, is more sensitive than PCA, and is not influenced by high serum IgE levels in the recipient animal.

Immunological unresponsiveness to helminth parasites. II. Antibody response and hypersensitivity reaction associated with Nippostrongylus brasiliensis infection in young rats.

Abstract We have previously shown that in rats infected when under 6 weeks of age with N. brasiliensis worm expulsion occurs only if more than 200 worms are established in the intestine. In such cases, worm expulsion starts later and proceeds at a slower rate than in comparatively infected adult rats stopping when a worm burden of 200 is reached. This relatively large residual infection persists into adult life. In the present paper the antibody status of rats infected when young was examined. Passive protection tests using the serum from such rats showed that protective antibody was produced by rats infected with more than 800 larvae, despite the fact that in these rats worm expulsion did not proceed to completion. It was also found that young rats produced reaginic antibody comparable in time of appearance and titer with similarly infected adults. Allergen production by the worms of the persistent infection was titrated and found to be produced in unreduced amount for at least 40 days after infection. Intestinal mast cell counts of the unresponsive rats were similar to those of infected adult rats. It was concluded that the incomplete expulsive reaction of rats infected when young cannot at present be explained by the absence of protective or reaginic antibodies or by a deficiency in the number of intestinal mast cells.

The Effect of Various Adjuvant Regimens and of Nematode Infection on the Reaginic Antibody Response to Egg-Albumin in the Rat

The role of some critical components of the potentiated reagin response to egg-albumin following nematode infection in the rat are examined. The phenomenon can conveniently be described in two stages: Stage 1. Following injection of the antigen reagin production must be initiated before infection with the parasite. To satisfy this precondition, egg-albumin requires to be injected with an adjuvant since no detectable reagin appears if the antigen alone is injected. Adjuvants found to be successful in this system were Bordetella pertussis, Freund’s complete or incomplete adjuvants, Corynebacterium parvum in water-oil emulsion and aluminium hydroxide gel. C. parvum in saline suspension proved ineffective. Stage 2.Nippostrongylus brasiliensis infection potentiates the circulating reagin titre up to 100 times. Attempts to potentiate by substituting B. pertussis for a parasite infection in stage 2 were unsuccessful.

Production of IgE and Reaginic Antibody in Rats in Relation to Worm Infections

Natural or experimental infection with live worm parasites is the most effective known stimulus for the production of IgE, resulting generally in higher levels of both antibody and total IgE than can be elicited by any other means. This general proposition is put into perspective by adding that virtually all animals are naturally infected with helminth parasites as are indeed the majority of human beings. Hookworm infection alone affects about 400 million people.

Immunological unresponsiveness to helminth parasites: III. Challenge of rats previously infected at an early age with Nippostrongylus brasiliensis

Abstract We have previously shown that when rats are infected when young with 500 N. brasiliensis larvae worm expulsion does not occur as in adult rats; instead rats so infected remain unresponsive to their intestinal worm burdens well into adult life. It was subsequently shown that this state is to a certain extent dose dependent in that infections of a greater size do result in a measure of worm expulsion but that this ceases when a burden of approximately 200 is reached; this also persists into the adult life of the rats. In this paper the response of rats infected when young to a subsequent challenge infection has been studied. Three factors have been found to be of importance in determining the type of response elicited: 1. (1) The size of the first infection given when young. Young rats initially infected with a small dose of larvae (500) respond to a challenge of 1000 larvae in adult life by a pattern of worm expulsion similar to rats experiencing a primary infection of N. brasiliensis , whereas rats initially infected with a large dose (3200) show a secondary type of response. 2. (2) The size of the challenge infection. Whereas removal of the original worm population by thiabendazole and its replacement with a similar small number of new worms (either by infection with larvae or by adult worm transplant) results in a primary type of worm expulsion, a large challenge infection (3000) larvae is capable of eliciting a secondary type of expulsion response despite an initial small infection. 3. (3) The age of the rats at the challenge infection. The superimposition of a challenge infection on a primary infection where both occur during the original unresponsive period (i.e. up to 7 weeks) results merely in a continuation of the unresponsive state into adult life although the worm burden is again adjusted to bring it down to a level of around 200 worms. It was concluded on several grounds that immune tolerance in the classical sense is not responsible for the persistence into adult life of the relatively large worm burdens acquired from infection during the immunologically unresponsive period. Alternative explanations and the significance of the phenomenon are discussed.

Stimulation and Suppression of IgE Antibodies by Antigens Presented to Mucosal Surfaces

Experiments in rats and mice have shown that antigens absorbed across mucous membranes may give rise to an IgE response, or alternatively to the suppression of IgE responsiveness through the activation of immunoregulatory mechanisms. Which of these alternatives occurs seems to depend on an interaction of extrinsic factors including dose and form of antigen presentation with the intrinsic immune reactivity of the animal, which may in itself be influenced by previous events. The available evidence for these statements will be reviewed.

Bone Marrow Differentiation

This workshop covered diverse topics which were nominally related in that they included the characterisation and regulation of differentiation of pluripotent hematopoietic stem cells and their progeny into B cells, mast cells and other leucocytes.