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SummaryIn this study we have examined serum from patients with Plasmodium falciparum malaria, collected at the time of acute attack and 14 days later. We have also examined sequential samples of sera taken from children living in Madang Province, Papua New Guinea, an area endemic for malaria. The total amount of antibody directed against P. falciparum in acute phase sera was less than that found in matched controls. An in vitro assay measuring inhibition of penetration of uninfected erythrocytes by merozoites of P. falciparum revealed less inhibitory activity in acute phase sera than in matched controls. The longitudinal study of sera from village children demonstrated that non-specific inhibition of intracellular parasite growth was fairly stable, while merozoite inhibiting activity was unstable and varied with time. A cloned P falciparum species has been used to directly demonstrate the specific growth enhancement by serum in vitro.Australian Journal of Experimental Biology and Medical Science (1986) 64, 229–235; doi:10.1038/icb.1986.25

SummaryThe kinetics of T lymphocyte responses to mucosally presented antigen and the appearance of antigen-reactive T cells in mucosal and systemic tissues have been investigated by measuring secondary mixed lymphocyte culture reactivity after intestinal administration of alloantigens. The data indicate that T lymphocytes in the intestine are able to respond to mucosally presented alloantigens, and that following immunisation the T cell reactivity occurs first in Peyer's patches then sequentially in mesenteric lymph nodes, thoracic duct lymph, gut lamina propria and distant mucosal sites. The response was mucosally restricted and the ultimate location of antigen-reactive cells is influenced by site of antigen administration. Evidence is also presented for the existence of systemic non-reactivity to mucosally presented antigens.Australian Journal of Experimental Biology and Medical Science (1984) 62, 687–699; doi:10.1038/icb.1984.65

SummaryThe immune function of lymphocytes isolated from human mesenteric lymph nodes (MLN) has been examined. Large yields of viable lymphocytes were obtained from MLN without the need for using enzyme or mucolytic agents. In comparison to gut mucosal lymphocytes MLN lymphocytes (MLNL) were technically easier to manipulate and to use in providing a more quantitative analysis of T-B cell interaction. The results presented indicate that the pattern of immunoglobulin secretion and immunoregulution of lymphocytes isolated from MLN was similar to that in cells isolated from the lamina propria, supporting that MLN constitute an important component of gut-associated lymphoid tissue (GALT).Australian Journal of Experimental Biology and Medical Science (1984) 62, 531–537; doi:10.1038/icb.1984.50

SummaryIn this study we have modified a micro Plasmodium falciparum in vitro growth inhibition assay to allow dissection of growth inhibition induced by test sera into two categories: inhibition of intracellular schizont growth and inhibition of uptake of merozoites into a second cohort of erythrocytes. This was achieved using morphology-controlled synchronised cultures with incubation times restricted to cover either ring to schizont development or schizont to ring development. Sera tested were obtained from a large prospective study of healthy residents of Madang, Papua New Guinea, who were carefully documented with respect to presence of malarial parasites in the blood, spleen size, age, sex and history of fever. In the ring to schizont assay sera from all the children tested inhibited parasitic growth by at least 20%, compared to only 10 of 39 adults tested (P < 0.0005). In the schizont to ring assay 20 of 39 adult sera tested inhibited the uptake of 14C-isoleucine into P. falciparum protein compared to 3 of the 15 children's sera tested (P < 0.01). These results are interpreted as reflecting a switch from non-specific mechanisms of resistance with increasing age.Immunology and Cell Biology (1985) 63, 513–520; doi:10.1038/icb.1985.55

SummaryA local antibody response occurred in the small intestine when immune sheep were challenged with the enteric nematode parasite, Trichostrongylus colubriformis. Incoming infective larvae stimulated the appearance of increased numbers of IgA-containing lymphocytes in intestinal lymph. There were increases in the populations of IgA- and IgG1-containing plasma cells in the lamina propria. This did not occur in regions of the small intestine distant to the habitat of T. colubriformis. Challenge infection in immune animals increased the titre of anti-T. colubriformis haemagglutinating antibody in serum, intestinal lymph, intestinal fluid and extracts of intestinal mucosa. Although immune intestinal lymph contains anti-T. colubriformis antibody of IgA isotype, which is presumably produced in intestinal lamina propria, it failed to transfer passive immunity against the parasite. This result, however, does not exclude the possibility that IgA-antibody responses are important in protective immunity against T. colubriformis.Australian Journal of Experimental Biology and Medical Science (1980) 58, 167–177; doi:10.1038/icb.1980.17

SummaryStudies were made on the origin and mechanism of transfer of IgG1, IgG2, IgA and IgM into the secretion of isolated loops of jejunum of unanaesthetized sheep. IgA was the major immunoglobulin in intestinal secretion, although considerable quantities of IgG1and IgG2were also present. Secretion: serum radioactivity ratios for IgG1and IgG2were similar, indicating that they were transferred into intestinal secretion with equal facility. Specific radioactivities of the various immunoglobulins in serum and secretion were compared and the results suggested that all the IgG2and most of the IgG1were derived from blood plasma, whereas only a trivial amount of the IgA was plasma-derived. The slow equilibration of IgM, together with its relatively short biological ‘half-life', prevented accurate assessment of plasma contribution of this immunoglobulin.Australian Journal of Experimental Biology and Medical Science (1974) 52, 711–716; doi:10.1038/icb.1974.70

SummarySome changes produced in the cell populations of intestinal lymph by infection with the enteric nematode Trichostrongylus colubriformis. were studied in sheep regularly re-infused with all discharged lymph. Lymphocyte traffic through the intestinal lymphatic duct was reduced until day 35 of primary infection, mainly due lo the- absence of lymphocytes with smaller cell volumes but was increased two-fold after day 70 and in immune sheep. Antigen-reactive lymphocytes in Mood and lymph were assayed by the uptake of: 3H-thymidine in cell culture stimulated by extracts from the larvae of T. colubriformis. Cells from the blood and lymph of immune sheep were highly reactive to worm antigen. A relatively smaller reactivity was present in the blood of worm-free sheep and was abolished during the first 12 days of primary infection. Antigen-reactive cells were not detected in intestinal lymph until 12 days after primary infection, mid in vitro antigen reactive in intestinal lymph of immune sheep was increased after challenge with infective larvae. Responses to the mitogens, concanavalin A and phytohaemagglutinin in cultures of cells from both intestinal lymph and blood were depressed on days 7 and 12 of primary infection.It is proposed that the diminished traffic of lymphocytes in intestinal lymph and the reduced numbers of mitogen and nematode antigen-reactive lymphocytes in both blood and intestinal lymph during the early stages of infection with T. colubriformis is closely related to the slow development of protective immunity to this parasite.Immunology and Cell Biology (1977) 55, 509–522; doi:10.1038/icb.1977.51

SummaryThe turnover rate and pool volume of radiolabelled autologous IgG1was similar to homologous IgG1in adult sheep. In neonatal lambs there was no significant difference for either of these parameters between homologous serum IgG1and maternal colostrum IgG1. However, the pool volume for IgG1expanded by approx. 30% over the experimental period in the lambs. When the turnover rates were corrected for this increase they were found to be similar to those observed for IgG1in adult animals.Australian Journal of Experimental Biology and Medical Science (1979) 57, 147–150; doi:10.1038/icb.1979.15

SummaryA study of immunoglobulin and albumin concentrations and the flow of intestinal lymph was made in sheep during infection with the parasitic nematode, Trichostrongylus colubriformis. Observations were made on uninfected worm-free sheep, on worm-free sheep undergoing primary infection and on immune sheep undergoing challenge infection.The flow of intestinal lymph and the concentrations of IgG1, IgG2and IgM in intestinal lymph and IgG2and IgM in blood plasma remained relatively constant during both primary and challenge infection. The concentration of IgA in intestinal lymph and blood plasma increased as early as day 6 of primary infection and maximum values were observed at day 34. By day 34 of primary infection the concentration of IgG1in blood plasma was significantly greater than that found in worm-free controls. Plasma IgG1, concentrations in resistant sheep were also significantly greater than those observed in worm-free controls. Challenge infection in immune sheep did not raise the concentration of IgA in intestinal lymph and blood or IgG1in blood.An indirect haemagglutination test was used to detect antibodies to T. colubriformis. Primary infection did not increase anti-worm antibody titres in either intestinal lymph or serum. Significant antibody titres were present in serum and lymph from immune sheep and were rapidly increased by challenge infection. Most antibody activity in serum was associated with IgM, whereas that in intestinal lymph was associated with IgA. These observations indicate the occurrence of a local antibody response to T. colubriformis in the intestine of immune sheep.Australian Journal of Experimental Biology and Medical Science (1978) 56, 225–235; doi:10.1038/icb.1978.24

SummaryRadiotracer techniques were used to compare the kinetics of IgG1and IgG2metabolism in sheep (1) prior to parasite exposure, (2) during an initial patent infection with Trichostrongylus colubriformis, and (3) during continuous exposure to the parasite when the animals were exhibiting resistance. Plasma concentrations of IgG1, IgG2, IgA and IgM were also monitored throughout the experiment.Plasma IgG1concentration increased significantly during the development of resistance and maintained this higher level on further exposure to the parasite. IgA concentration was also elevated during the development of resistance to a level approximately three times that observed prior to initial infection, hut this increase was only transitory. No significant changes in either IgG2or IgM concentration occurred.Analysis of the radiotracer data for IgG1and IgG2, was based on a two-compartment model comprising intravascular and extravaseular protein pools with reversible exchange between them and irreversible loss from the intravascular site. No significant changes in compartment sizes or rates of exchange between compartments were recorded during measurement periods (1), (2) and (3) for either IgG1or IgG2. Rates of irreversible loss of IgG2were similar during (1), (2) and (3); the irreversible loss of IgG1was unaltered following the initial infection but Increased by approximately 50% during period (3).It is concluded that increased synthesis of IgG1in resistant sheep continually exposed to T. colubriformis occurs as a result of antigenic stimulation rather than as a consequence of increased loss of plasma into the intestine.Australian Journal of Experimental Biology and Medical Science (1978) 56, 181–194; doi:10.1038/icb.1978.20

SummarySome aspects of the local immune response to nematode infection were examined by introducing fourth-stage Trichostrongylus colubriformis larvae into Thiry-Vella loops in worm-free and T. colubriformis-resistant sheep. Approximately 15% of the larvae introduced into the worm-free sheep survived and matured into adult worms, whereas less than 1% survived in resistant sheep. The amount of IgG1, IgG2, IgM and albumin discharged from loops in worm-free hut not resistant sheep all increased following infection with larvae. Secretions from resistant sheep contained approximately three times as much IgA as secretions from the worm-free group and. in addition, their plasma IgG1level was significantly higher. Antibodies against T. colubriformis were found in both plasma and intestinal secretions, the highest titres being found in the resistant sheep. During worm expulsion from loops in the resistant sheep neither immunoglobulin levels nor antibody titres in the secretions increased significantly.Australian Journal of Experimental Biology and Medical Science (1978) 56, 99–106; doi:10.1038/icb.1978.10

SummaryThe experiment comprised two sections. First, radiotracer techniques were used to study the metabolism of IgG1and IgG2in 5 non-pregnant and 4 pregnant ewes. In the pregnant ewes, the rates of synthesis for IgG1and IgG2were similar to the rates observed in non-pregnant animals. However, the irreversible loss of IgG1was significantly greater than IgG2in pregnant ewes and IgG1in non-pregnant ewes. Additionally, it was found that most of the IgG1and virtually all of the IgG2in mammary secretion was serum derived.Secondly, the levels of sodium, potassium and lactose and the selective index for IgG1in mammary secretions of 5 pregnant ewes were monitored over the parturient period. The values of all the measures remained relatively constant until one day before parturition. From one clay pre-partum, the levels of potassium and lactose in mammary secretion began to increase and had risen 2-3 fold by 5 days post-partum. Over the same period, the selective index for IgG1decreased 20 fold, whereas the level of sodium fell from approximately 32 mmol/l to 18 mmol/l. The concentration of IgG1in plasma slowly declined from approximately 23 g/l to 15 g/l over the last 10 days of pregnancy.During the parturient period, the decline in plasma IgG1levels, in comparison with IgG2, without alteration in the rates of synthesis of either immunoglobulin, supports the hypothesis that selective transport of IgG1into mammary secretion occurs without degradation. The results also indicate that the transport of sodium and potassium into mammary secretions are altered over the parturient period.Australian Journal of Experimental Biology and Medical Science (1976) 54, 337–348; doi:10.1038/icb.1976.34

SummaryA comparative study was made on the secretion of IgG1and IgA into parotid and submaxillary saliva of sheep. The purpose of the study was to examine the suggestion that in the external secretory organs of ruminants there is an inverse relationship between the capacity to selectively transfer IgG1and the development of the IgA secretory system. Despite a marked difference in the secretion of IgA between the parotid and submaxillary salivary glands, the magnitude of selective transfer of IgG1was similar. Thus, there appears to be no relationship between the selective transfer of IgG1and the secretion of IgA into the saliva of sheep.Australian Journal of Experimental Biology and Medical Science (1976) 54, 191–195; doi:10.1038/icb.1976.19

SummaryIn non-pregnant adult sheep biological ‘half-lives’ of IgG1and IgG2were approximately 8 days with those for lambs slightly less than 7 days. In contrast, in late pregnant ewes forming colostrum the ‘half-life’ of IgG1was only 3·7 days. This value was significantly less (P < 0·01) than for IgG2and less (P < 0·001) than the value for IgG1in non-pregnant animals.Australian Journal of Experimental Biology and Medical Science (1974) 52, 717–719; doi:10.1038/icb.1974.71