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Effect of dietary protein supplementation on the development of immunity to Ostertagia circumcincta in growing lambs.

Thirty four-and-a-half-month-old worm-free lambs were used to determine whether the rate of development of immunity to Ostertagia circumcincta infection in growing lambs could be influenced by the addition of a by-pass protein supplement. Sixteen lambs (groups 1 and 2) were fitted with an abomasal catheter and infected daily with 2000 O circumcincta L3 for eight weeks. Group 1 lambs received 45 g of crude protein day-1 (sodium caseinate) as a continuous infusion into the abomasum from week-1 to week 8. At week 9, groups 1 and 2, together with eight naive controls (group 3), were treated with anthelmintic and challenged one week later with 50,000 O circumcincta L3 and killed after a further 10 days. An additional six worm-free lambs provided feed intake and growth rate data. All the lambs were offered a complete ruminant ration (167 g crude protein kg-1) ad libitum. The cumulative liveweight gain of both the trickle-infected groups was less than that of the controls. The mean faecal egg counts were lower in group 1 from day 39 after infection and the mean worm burdens were significantly lower than in group 2. Total Ostertagia populations did not differ significantly between group 3 and either group 1 or 2 lambs. Early L4 stages constituted a greater percentage of the total worm population in group 1 (79.5) and group 2 (48.5) than in the challenge controls (group 3) (20.4). The trickle-infected lambs also had higher concentrations of gastric mast cell protease which correlated positively with the proportion of early L4 stages and negatively with the total worm burden. The provision of by-pass protein supplement accelerated the development of immunity to O circumcincta in these lambs.

Animals↗

Development of immune complexes in the skin.

Complement activation by immune complexes induces inflammation, but during this process the nature of the complexes is altered. Once immune complexes have attained sufficient lattice to activate complement, further increase of the lattice and immune precipitation are limited by the incorporation of complement components. The presence of complement components in immune complexes facilitates their disposal from circulation by complement receptors on red cells in humans. Without complement activation the disposal of immune complexes of sufficient lattice is mediated by Fc receptors. The development of immune deposits in tissues can arise by several mechanisms. Circulating immune complexes may be deposited in a number of vascular beds. Immune deposits in tissues may also arise by local formation. This process may involve structural antigens in tissues, cell surface antigens that are shed after interaction with specific antibodies or antigens that have become planted in tissues and then combine with antibodies. Charge-charge interactions enhance deposition of immune complexes in several organs, involving fixed negative charges in tissues and positive charges on antigens or antibodies in immune complexes. Successful detection of immune deposits in dermal vessels requires the examination of fresh lesions. Local vascular changes contribute significantly to deposition of immune complexes in dermal vessels. Charge-charge interactions enhance this deposition and contribute to the development of deposits at the dermal-epidermal junction in experimental animals.

Animals↗

Studies of missed opportunities for immunization in developing and industrialized countries.

Missed opportunities for immunization are an obstacle to raising immunization coverage among children and women of childbearing age. To determine their global magnitude and reasons, studies reported up to July 1991 were reviewed. A standard measure for the prevalence of missed opportunities was calculated for each study. Seventy-nine studies were identified from 45 countries; 18 were population-based, 52 were health-service-based, and 9 were intervention trials. A median of 32% (range, 0-99%) of the children and women of childbearing age who were surveyed had missed opportunities during visits to the health services for immunization or other reasons. Missed opportunities were mainly due to failure to administer simultaneously all vaccines for which a child was eligible; false contraindications; health workers' practices, including not opening a multidose vaccine vial for a small number of persons to avoid vaccine wastage; and logistical problems. To eliminate missed opportunities for immunization, programmes should emphasize routine supervision and periodic in-service training of health workers which would ensure simultaneous immunizations, reinforce information about true contraindications, and improve health workers' practices.

Adult↗

Complement: an inflammatory pathway fulfilling multiple roles at the interface of innate immunity and development.

Complement has been long perceived as an innate immune system that plays a pivotal role in the maintenance of host defense against infectious agents and the propagation of pro-inflammatory responses in the context of human disease. Complement activation has been associated with the onset of acute inflammatory reactions leading to complications such as acute graft rejection, local tissue injury and multi-organ failure. However, recent studies have indicated that various complement activation products may exert a beneficial effect by contributing to critical developmental and regenerative processes. Appreciating this extraordinary 'versatility' of complement proteins provides a framework for revisiting the design of effective complement therapeutics. A balanced strategy will have to consider limiting the detrimental proinflammatory effects of complement while preserving those activities that promote tissue repair and regeneration, cell survival and early development.

Animals↗

The spontaneous development of immune complex type glomerular lesions in outbred mice is dependent on environmental factors and sex.

To investigate the role of environmental factors in the spontaneous development of immune complex glomerulonephritis in the mouse, follow-up studies of various immunological parameters and of kidney lesions have been done in male and female outbred OF1 mice housed from birth to four months of age in two different conditions: (a) in a conventional animal house; (b) in a "controlled" animal house designed for long-term studies on nude mice. Female mice housed under conventional conditions develop mild to intense glomerular lesions with granular deposits of immunoglobulins and C3 after two months of age. The appearance of these lesions is correlated with a sharp increase of various IgG subclasses levels at two months of age. Female mice housed under "controlled" conditions do not show such an increase and have only scarce to mild lesions until four months of age. In male mice, similar observations are done but the differences in immunological parameters and in histopathological findings between the two groups of mice according to the housing conditions are less noticeable. The environmental factors which are involved in the development of these immune mediated lesions are not known; it is hypothetized that infectious agents play a role. This study emphasizes the importance of housing conditions and of sex in immunopathological investigations in the mouse and the possible bias these conditions may introduce, in some experiments.

Animals↗

Influence of source and quantity of protein on the development of immunity and resistance to African trypanosomiasis.

Although it is well documented that severe protein deprivation inhibits the development of the immune response and exacerbates certain infections, little has been done to study the effects of native diets on endemic diseases or immunity. Therefore, protein-restricted diets were formulated for mice to mimic the sources and amounts measured in human diets of the Batouri region of Cameroon, endemic for African trypanosomiasis. Weanling C57BL/6 female mice were fed a diet that contained 73% of the recommended daily allowance (RDA) of protein. The sources of protein were all plant (cornmeal), all animal (casein), or a ratio that reflected the native diet (2.2 parts plant to 1 part animal protein). Diets were isocaloric on a weight basis, equal in lipids, and adequate in vitamins and minerals. Control mice were fed laboratory chow or two times the RDA of animal protein (casein). Mice fed only cornmeal or the native diets consumed as much food but did not gain as much weight as mice fed only animal protein, indicating the poorer quality of protein in their diets. Upon infection with Trypanosoma brucei gambiense, however, significantly higher numbers of these mice controlled the first peak of parasitemia and survived the infection as compared with mice fed the other three diets. Since all mice developed patent infections and the parasite growth rate was unaffected by diet, innate immune factors were ruled out as the cause for the higher level of resistance to the parasite. To determine whether diet affected the development of the immune system, weanling mice were maintained on diets for 30 days before immunization with sheep erythrocytes or trinitrophenylated Ficoll. Mice fed only plant protein or native diets elicited higher direct plaque-forming-cell responses to both the T-cell-dependent and T-cell-independent antigens. Since variant-specific immunity which controls levels of African trypanosomes in the blood is a T-cell-independent humoral immunoglobulin M response, this suggests that cornmeal, a protein of poor quality, was adequate for the development of humoral immunity and resistance to African trypanosomiasis while casein, an animal protein of high quality, was not. This provides more evidence that diet plays an important role in infection and immunity.

Animals↗

Early nutrition and the development of immune function in the neonate.

The present review will concentrate on the development of the gut-associated lymphoid tissue and the role of early nutrition in promoting immune function. The intestine is the largest immune organ in the body, and as such is the location for the majority of lymphocytes and other immune effector cells. The intestine is exposed to vast quantities of dietary and microbial antigens, and is the most common portal of entry for pathogens, some of which are potentially lethal. The development of normal immune function of the intestine is therefore vital for survival, and is dependent on appropriate antigen exposure and processing, and also an intact intestinal barrier. In early life innate mechanisms of defence are probably more important than active or adaptive mechanisms in responding to an infectious challenge, since the healthy neonate is immunologically naïve (has not seen antigen) and has not acquired immunological memory. During this period maternal colostrum and milk can significantly augment resistance to enteric infections. The mechanisms of enhancing disease resistance are thought to be passive, involving a direct supply of anti-microbial factors, and active, by promoting the development of specific immune function. A tolerance response to dietary and non-invasive antigens is generally induced in the gut. However, it must also be able to mount an adequate immune response to ensure clearance of foreign antigens. It is now recognized that regulation of tolerance and active immune responses is critical to health, and failure to regulate these responses can lead to recurrent infections, inflammatory diseases and allergies. The education of the immune system in early life is thought to be critical in minimizing the occurrence of these immune-based disorders. During this phase of development maternal milk provides signals to the immune system that generate appropriate response and memory. One factor that has been proposed to contribute to the increase in the incidence of immune-based disorders, e.g. atopic diseases in Western countries, is thought to be the increased prevalence of formula-feeding.

Animals↗

Effects of prednisolone on the development of immune responses to canine distemper virus in beagle pups.

Effects of oral prednisolone (OP) on the development of immune responses of Beagle pups to canine distemper virus (CDV) were studied. Dogs were treated with OP for 21 days, twice a day for the first 7 days, once a day for the next 7 days, and on alternate days for the last 7 days. Dogs given dosages of OP (1 mg/kg and 10 mg/kg) showed a normal in vivo immunogenic response after CDV vaccination and survived a virulent CDV challenge exposure, whereas non-treated, nonvaccinated dogs became ill or died after challenge exposure. The most marked effect of corticosteroid treatment on the immune system was the graded phytoimmunosuppressive effect upon the lymphocyte blast transformation test.

Administration, Oral↗

Development of immune response during typhoid fever in man.

The development of both humoral and cell-mediated immune responses (CMIR) to antigens prepared from Salmonella typhi was investigated in patients suffering from typhoid fever. The antibodies were determined by the standard Widal test while the leucocyte migration test was used for CMIR. These immunological parameters were correlated with the duration of illness, the duration of chloramphenicol therapy and the severity of the illness. It was found that CMIR appeared after the first week of illness in uncomplicated cases of typhoid fever, where as it remained negative in the patients who had complications. The antibody titres were similar in the two groups. On further follow up of complicated cases, the clinical recovery coincided with the development of CMIR. It may be concluded that for recovery in typhoid fever CMIR is more important than antibodies.

Adult↗

Effects of chloramphenicol on the development of immune responses to canine distemper virus in beagle pups.

The effect of oral chloramphenicol (CHPC) on the development of immune responses to canine distemper virus (CDV) in Beagle pups was studied. Dogs were treated with CHPC for 14 days at a dose of 50 mg/kg, three times a day. Hematologic changes in CHPC-treated dogs included: polychromasia, anisocytosis, and target cell formation of red blood cells concurrent with vacuolation of lymphocytes and basophilic granule formation in neutrophils. Dogs given this therapy showed normal in vivo and in vitro immune responses after CDV vaccination and survived a virulent CDV challenge, whereas untreated, unvaccinated dogs became ill or died after challenge exposure. The results of this study indicate that CHPC therapy does not interfere with either the prechallenge immune response to attenuated viral antigen or the efficient immune mechanisms invoked during virulent virus challenge.

Animals↗

Hypothetical thinking on influences of chemicals in the environment and female sex hormones in food on Japanese children.

Allergic diseases have rapidly increased in Japan. Changes in the prevalence of bronchial asthma in children and birth years of anaphylactic patients suggest that an event that may have increased allergic diseases occurred in about 1970, and chemicals in the environment and food are considered to be a cause. Some environmental pollutants inhibit the development of the immune system, and such chemicals possibly affect immune development from the fetal period. Female hormones contained in milk, meat and eggs may also affect the development of the immune system after birth. It may be possible that a cause of the current increase in allergic diseases, the disruption of Th1 (T lymphocyte helper type 1)/Th2 (T lymphocyte helper type 2) balance, occurs due to a complex influence of chemicals and excess female hormones, and the development of the immune system may be affected in children in whom hormone production is physiologically low, particularly boys before puberty. The influences of chemicals and sex hormones in food have not been fully investigated, and future studies are expected.

Adolescent↗

Intestinal absorption of colostral lymphocytes in newborn lambs and their role in the development of immune status.

Two model experiments were conducted to study the intestinal absorption of colostral lymphoid cells and the role of these cells in the development of immune status in newborn lambs. In experiment I, 17 lambs of 14 Merino ewes were used. Suspensions of lymphoid cells separated from the colostrum (cell density: 5 x 10(6)/ml) and blood (3 x 10(6)/ml) were labelled with technetium (Na99mTcO4) of 37 MBq/ml radioactive concentration. In three groups of lambs, 10-ml volumes of the cell suspensions were injected directly into the duodenum after laparotomy, while in a fourth group (group Ia) the same volume was administered to the animals through an oesophageal tube. The labelled cells revealed that colostral cells of the lamb's own dam are absorbed from the gastrointestinal tract and get into the newborn lamb's lymph circulation irrespective of the route of application. In experiment II, involving 40 lambs of 40 ewes, we studied the effect of absorbed colostral lymphocytes on the development of the newborn lamb's immune status. Twenty ewes (group A) each were treated with 3 ml tetanus anatoxin twice, while the remaining animals (group B) were left uninoculated. Lambs of group A (designated A2) were separated from their dams immediately after birth, then were administered, through an oesophageal tube, 10 ml of a suspension of lymphoid cells (cell density: 5 x 10(6)/ml) separated from the maternal colostrum. Subsequently, the lambs were interchanged with lambs of nonimmunized ewes of group B (designated lambs B1), i.e. were mutually put out to nursing. At three days of age, lambs of groups A1, A2, B1 and B2 were inoculated with 3 ml tetanus anatoxin, then blood samples were taken from them 5 times in a period of 27 days for comparative examination of the humoral and cellular immune reactions. The results demonstrate that lymphoid cells from the colostrum of the lambs' own dam become absorbed into the newborn lambs' lymph circulation, remain immunologically active and may transfer, besides immunological memory, also cellular activity.

Animals↗

Development of immunity to coccidiosis in chickens administered anticoccidials in feed.

New combinations of techniques were employed for comparing the development of immunity of Eimeria tenella in chickens being medicated with 12 different anticoccidials. Broiler-type birds in batteries received a daily measured dose of E. tenella oocysts for 15 consecutive days while the drug was administered at the manufacturer's recommended level. Two or more tests of each drug gave the following ratings: strong suppression, monensin (121 ppm), salinomycin (80 ppm), lasalocid (75 ppm); moderate suppression, monensin (100 ppm), decoquinate (30 ppm), clopidol (125 ppm), and narasin (80 ppm); slight suppression, arprinocid (70 ppm), nicarbazin (125 ppm), and amprolium (125 ppm + ethopabate (4 ppm); no effect, robenidine (33 ppm), zoalene (125 ppm), and aklomide (250 ppm).

Amprolium↗

Effects of thyroid hormone on the development of immune system in zebrafish.

Effects of thyroxine (T4) and methimazole (MMI) on the development of the zebrafish immune system were investigated using continuous immersion treatment experiments. The effects of the treatments on thymus development were determined using computer-aided thymus morphometric analyses on in situ hybridization serial sections of the thymus while the effects on immune-related gene expression levels were monitored using quantitative real-time PCR. The findings indicate that thymus development and thymopoiesis, as indicated by thymus size, thymus Rag-1-positive region, and TCRAC expression level, were affected by T4 and MMI-treatments. With the exception of Ikaros, MMI-treated fish has lower immune-related gene expression levels, although it is not certain whether the effect resulted indirectly from the concomitant growth-retardation and/or directly from an effect on lymphopoiesis itself. The findings were comparable with those in mammalian system, thus providing the first evidence that the thyroid relationship with thymus development and lymphopoiesis is likely to be conserved from fish to higher vertebrates. It suggests the possibility of using zebrafish as a model system to investigate the molecular mechanisms involved in thyroid hormone-dependent disorders in the immune system.

Animals↗