Virtually all the components of nematodes have been reported to be antigenic to some extent, but as the contact of tissues with the host is restricted, when the parasites are alive, it is unlikely that these antigens act as immunogens. It is more probable that the antigens which evoke a strong immunity are the w o r m ’s secretory pro
ducts .
The concept, of the protective antigens being released from the parasite, first came from the work of Sarles (1938), who demonstrated precipitates at the orifices of N. brasiliensis larvae in immune serum in vitro. Edwards, Burt and Ogilvie (1971) and Sanderson and Ogilvie
(1971) suggested that the enzymes produced by adult N. brasiliensis were the important protective antigens. Four enzymes, aminopeptidase, non-specific esterase, acid phosphatase and acetylcholinesterase
(AChE) were detected in the adults (Lee, 1970).
AChE was secreted from the anterior glands of adult and L4 worms, but not from infective larvae (Lee, 1970) and only this enzyme was considered to be important as an immunogen as its production, by the worms, was closely linked to the immune response, being increased in the presence of antibodies and decreased in their absence (Sanderson, 1969» Lee, 1970» Sanderson and Ogilvie, 1971» Edwards et a l ., 1971»
Jones and Ogilvie, 1972) . AChE reduces peristalsis of the gut and aids the worm's maintenance in situ (Symons, 1966» Ogilvie and Jones, 1971). As worms became damaged, the Increase in AChE levels was coupled with an alteration in the proportions of its isoenzymes
(Edwards et al., 1971). AChE has three isoenzymes, A, B and C and antibodies associated with IgG, were detected to all three (Jones,
o
xj
1Edwards and Ogilvie, 1970). The antibody response had its strongest activity against the isoenzyme A, but antibodies were induced more readily by the B and C isoenzymes; no antibodies were found against the worms' non specific esterases, aminopeptidases or acid phosphatases
(Ogilvie and Jones, 1971).
The functional antigens of T. spiralis are secreted from the multicellular stichosome (Despommier and Muller, 1970b), an organ which occupies the anterior third of the muscle larvae and adult worms and consists of large stichocyte cells, filled with granules which are secreted through the oesophagus (Despommier and Muller, 1970a). The granules are of 3 types; alpha, beta^ and b e t a ^ ; the smaller beta^ granules are the important antigens; they w ere purified and were shown to be strongly immunogenic and to elicit a protective immune response (Despommier and Muller, 1969; Despommier and Muller, 1970a). Microgram quantities were capable of protecting mice and rats against all stages of a subsequent challenge. However, lower stimu
lating doses of the antigen served only to reduce female fecundity (Despommier, Campbell and Blair, 1977). This work illustrates the degree of control, on the immune response, available when purified antigenic materials are used.
5. The thymus dependency of the immune response
The majority of antigens are thymus dependent, in that they require the presence of thymus derived cells to induce an immune response. The absence of a functional thymus and thymus derived cells allowed a greatly prolonged life span of adult T. spiralis worms in nude mice (Ruitenberg, 1974; Ruitenberg, Elgeroraa, Kruizinga and Leenstra, 1977a). Anti-thymocyte serum (ATS) prevented rats and mice
m m .
rr
from developing protective immunity to T. spiralis (Kozar, Karmanska, Kotz and Seniuta, 1971; Larsh, Weatherly, Goulson and Chaffee, 1972;
Mackinicka, 1972; Walls, Carter, Leuchars and Davies, 1973). The increase in the number of plasma cells in the intestinal mucosa of infected animals was thymus dependent (Ruitenberg, Leenstra and Elgersma, 1977b) as was the presence of intra-epithelial lymphocytes
(Parrott and de Sousa, 1974; Guy-Grand, Griscelli and Vassalli, 1974), the degranulation of intestinal mast cells coupled with IgE production
(Kelly, 1972; Ruitenberg, Teppema, Kruizinga, Elgersma and Steerenberg, 1975; Ruitenberg and Elgersma, 1976; Ruitenberg et a l ., 1977b) and the blood and tissue eosinophil response (Basten and Beeson, 1970;
Walls et a l ., 1973).
However, some degree of antibody formation, to infection with T. spiralis, has been found in thymectomised and irradiated CBA mice.
It was suggested that these immunoglobulins acted as blocking anti
bodies and that their production w a s stimulated by thymus independent antigens (Ljungstrflm and Ruitenberg, 1976). No antibody response to T. spir alis was noted in nude mice (Ruitenberg et a l . , 1977a) . This disparity could be due to the incomplete destruction of the thymus and thymus derived cells of the C B A mice or their possible genetically determined ability to respond to T-independent antigens.
The development of protective immunity to N. brasiliensls is also totally thymus dependent (Ogilvie and Jones, 1967; 1971; 1973;
Kelly, 1972; Ferguson and Jarrett, 1975).
II. THE COMPONENTS INVOLVED IN THE IMMUNE EXPULSION OF T. SPIRALIS AND N. BRASILIENSIS FROM THE INTESTINE OF THE HOST
1. Factors involved in the immunological response
T. spiralis and N. brasiliensis infections of the gut induce antibody formation, a cell mediated response and an inflammatory reaction. The infiltration of plasma cells, mononuclear cells, eosinophils and mast cells/basophils into the intestine have all been described (Taliafferro and Sarles, 1939; Larsh and Race, 1954; Ogilvie and Jones, 1973) .
Two main theories have been proposed to describe the mechanism of immunological expulsion of T. spiralis and N. brasiliensis from the gut. Briefly, Larsh and his co-workers (reviewed by Larsh and Race, 1975; Larsh and Weatherby, 1975) proposed that expulsion of these worms from the host was due directly to the inflammatory changes brought about by antigen sensitised lymphocytes and involved no humoral response. Ogilvie and Love (1974) suggested that immune expulsion was a complex mechanism requiring the sequential action of antibodies and sensitised lymphocytes. Antibodies caused cytological damage to the intestinal and genital cells of the worms (Ogilvie and Hockley, 1968;
Lee, 1969 ; Love, Ogilvie and McClaren, 1976), while sensitised lymphocytes, with the possible Involvement of inflaimatory cells, effected their expulsion from the host (Ogilvie and Love, 1974).
Present day knowledge suggests that the immune response against these worms may not be as stereotyped as suggested by these theories
(discussed later).
2