Antigen Absorption Research Articles

Allergic contact dermatitis in children.

DefinitionAllergic contact dermatitis (ACD) is an inflammatory reaction of the skin that follows percutaneous absorption of antigen from the skin surface and recruitment of previously sensitized, antigen-specific T lymphocytes into the skin.EpidemiologyIn the pediatric age group, ACD can involve either sex and manifest as early as the first week of life. A recent review of several European and US studies found that ACD may account for up to 20% of cases of dermatitis in the 0- to 14-year-old age group. Although the incidence and prevalence of the disease in the general pediatric population is unknown, epicutaneous patch testing of randomly selected and otherwise healthy children revealed that 13% to 20% were allergic to one or more common antigens, suggesting that at least 20% of children in the general population theoretically are at risk of developing ACD. When one considers poison ivy or poison oak as contact allergens prevalent in certain areas of North America, the likelihood of allergic contact dermatitis may be much higher. Pediatricians should recognize that children are sensitized to contact allergens early in life, with most children being sensitized by age 5 years. The allergens most commonly responsible for allergic contact dermatitis in North American children are listed in Table 1.

Analysis of antigenic determinants shared by two different allergens recognized by human T cells: house dust mite (Dermatophagoides pteronyssinus) and chironomid midge (Chironomus yoshimatsui).

To analyse the cross-reactivity of T-cell-mediated immunity between Dermatophagoides pteronyssinus (Dp) and Chironomus yoshimatsui (Cy), the most common allergens in Japan, we established antigen-specific human T-cell lines and clones. Some but not all of the Cy-induced T-cell lines showed a significant proliferative response not only to Cy, but also to Dp. No T-cell line responded to other unrelated antigens. When we stimulated the Dp-induced T-cell clones with Cy, 3 of the 40 clones (7.5%) showed a significant proliferation, and 2 of the 3 clones produced interleukin-4 and interferon-gamma, indicating their helper function. Cross-reactivity was diminished significantly after the absorption of Dp antigen in an anti-Cy affinity column. The cross-reactive epitopes were thought to be expressed on the Dp molecule of 45-53 kD. The presence of helper T cells reactive to both allergens suggests a possibility that this cross-reactivity might be involved in part in the high incidence of allergy to the 2 major allergens.

Vegetable foods in weaning.

Vegetable foods (cereals, non-starchy vegetables, legumes) make a unique nutritional and metabolic contribution during weaning. They provide proteins that are of low biological value individually but whose value can be raised by consuming appropriate combinations: minimal amounts of lipids, mostly essential polyunsaturated fats; complex carbohydrates; and soluble fibre, which are fermented by colonic flora to short-chain fatty acids that have beneficial effects. Insoluble fibre, minerals, trace elements and vitamins are also nutritionally important components of vegetable foods. Vegetable foods lower the calorific density of meals, modulate nutrient and antigen absorption, and promote a physiological copropoiesis. Recent nutritional surveys have shown that 12-month old children eat an excessive amount of animal proteins. Whole cereals and non-starchy vegetables, including whole legumes, should be routinely eaten during weaning to improve nutritional balance and to make children accustom to eating fibre, which has prophylactic properties. The daily intake of fibre should be progressively increased to 5 g during the first year of life.

Papaverine effects on PGI 2 and TXA 2 release from the canine vascular wall

Operative manipulation of blood vessels might lead to spasm, thereby destroying the endothelial cell function: the spasm can be prevented by the vasodilator papaverine. To study if this was mediated via the prostanoid pathway the following investigation was undertaken: canine jugular veins and carotid arteries were dissected with or without papaverine. Vessel segments were then perfused with Hank's balanced salt solution for five times 15 min. Prostacyclin was measured as the stable degradation product 6-keto-PGF 1α and thromboxane as TXB 2, by radioimmunoassay. Control arterial segments' 6-keto-PGF 1α release was initially 129.5 + 20.1 pg/ mm 2 15 min , and 29.7 + 10.4 after 60 min (p<0.05 vs initial value) and responded to arachidonic acid (AA) with an increase to 139.2 ± 23.1 pg/ mm 2 15 min (p<0.05). Segments treated with papaverine had the same release as the controls. In venous segments there was a lower initial release (p<0.05) from segments given papaverine than from controls, but this was more likely an effect of papaverine on the assay. There was no difference in release of prostacyclin from segments given papaverine in the perfusate compared to controls when using 125I tracer. When using 3H tracer including absorption of free antigen to dextran coated charcoal, papaverine displaced the free tracer giving artificially low values. There was no effect of papaverine given intraoperatively on the TXB 2 release, neither from arteries nor from veins. In another experiment the vessel wall tension was examined and the cyclooxygenase inhibitor diclofenac did not inhibit the vasodilating effect of papaverine. It is concluded that the vasodilating effect of papaverine is not mediated via prostacyclin release and that the vasodilating effect does not influence the prostacyclin release from arteries or veins. Finally, papaverine interacts with the 3H assay by displacing the antigen-antibody complex.

Effect of aging and caloric restriction on intestinal permeability

Intestinal permeability is increased in several disorders such as Crohn's disease or rheumatoid arthritis. Since aging leads to alteration of many biological functions, the effect of aging on intestinal permeability was studied by measuring the intestinal permeability in aging rats gavaged with different size permeability probes— mannitol, polyethylene glycol (PEG) 400, and inulin. In rats fed with control diet, there was a significant increase in intestinal permeability to medium size probes PEG 400 (14.8 ± 0.4 and 21.0 ± 1.1% at 3 and 28 months respectively, p < .01) and mannitol (3.41 ± 0.4 and 5.3 ± 0.5% at 3 and 28 months, respectively, p < .01). Intestinal permeability of the large macromolecule inulin did not change (0.42 ± 0.03 and 0.38 ± 0.02% at 3 and 28 months, respectively) with aging. There was no correlation between weight of the rats and their intestinal permeability. Because dietary caloric restriction has been found to prolong the life span, retard deterioration of several biological functions, and affect intestinal absorptive functions, we examined the effect of lifelong calorie restriction on intestinal permeability changes. Lifelong calorie-restricted diet did not affect age-related change in intestinal permeability. We conclude that intestinal permeability of medium size probes increases with aging and that lifelong caloric restriction does not prevent this change. We speculate that age-associated deterioration in intestinal barrier functions could permit increased systemic absorption of lumenal antigens and could perhaps contribute to the genesis of antigen-related age-associated diseases.

Prospects for human mucosal vaccines.

The selective induction of antibodies in external secretions and mucosal T cell-mediated immunity are desirable for the prevention of various systemic as well as predominantly mucosa-restricted infections. An enormous surface area of mucosal membranes is protected primarily by antibodies that belong, in many species, to the IgA isotype. Such antibodies are produced locally by large numbers of IgA-containing plasma cells distributed in subepithelial spaces of mucosal membranes and in the stroma of secretory glands. In humans and in some animal species, plasma-derived IgA antibodies do not enter external secretions in significant quantities and systemically administered preformed IgA antibodies would be of little use for passive immunization. Systemic administration of microbial antigens may boost an effective S-IgA immune response only in a situation whereby an immunized individual had previously encountered the same antigen by the mucosal route. Immunization routes that involve ingestion or possibly inhalation of antigens lead to the induction of not only local but also generalized immune responses, manifested by the parallel appearance of S-IgA antibodies to ingested or inhaled antigens in secretions of glands distant from the site of immunization. Convincing evidence is available that antigen-sensitized and IgA-committed precursors of plasma cells and T cells from IgA inductive sites (e.g., BALT, GALT, and tonsils) are disseminated to the gut, other mucosa-associated tissues, and exocrine glands. However, due to the limited absorption of desired antigens from the gut lumen of orally immunized individuals, repeated large doses of antigens are required for an effective S-IgA response. Novel antigen delivery systems for the stimulation of such responses has been briefly reviewed here. These, of course, include genetically engineered bacteria and viruses, CT/CFB, liposomes and microspheres. Live attenuated or genetically manipulated bacteria expressing other microbial antigens have been used for selective colonization of GALT. Unique antigen packaging and the use of adjuvants suitable for oral administration hold promise for an efficient antigen delivery to critical tissues in the intestine and deserve extensive exploration. The oral immunization route appears to have many advantages over systemic immunization; however, one must consider alternate IgA inductive sites and compartmentalization within the Common Mucosal Immune System. In addition to providing immunity on mucosal surfaces, which are the most common sites of entry of infectious agents, the mucosal routes of administration are more acceptable and do not require stringent criteria applicable for injectable vaccines, storage problems may be simplified, and large populations of individuals can be immunized simultaneously without the assistance of highly trained health personnel.

Enhanced enteric uptake of human gamma globulin by Quil-A saponin in Oreochromis mossambicus

The localisation of orally and anally delivered antigen (human gamma globulin, HGG) was investigated in the tilapian, Oreochromis mossambicus , using several sensitive immunohistochemical and immuno-electronmicroscopical techniques. The antigen was absorbed rapidly across the intestinal enterocytes (after 15 min) and was observed in intimate contact with a variety of cells in the epithelium and lamina propria including gut-associated lymphoid tissue cells. The transcytosed antigen was also observed in the vicinity of underlying intestinal capillaries within 1 h. Several novel delivery systems were used employing the saponin adjuvant Quil-A as a direct adjuvant and in combination with antigen in defined multimeric forms. Quil-A had a direct effect on the intestine of O. mossambicus and on the levels of absorption of HGG and its subsequent cellular localisation. The results demonstrate the ability of the intestine of tilapia to absorb and to have potentially relevant immune interactions with orally and anally delivered protein antigens and the potential of enhancing antigen absorption with saponin adjuvants.

Morphology of the gut associated lymphoid tissue of Oreochromis mossambicus and its role in antigen absorption

Gut-associated lymphoid tissue (GALT) was investigated in adult fish using histological procedures. GALT was present in all regions of the gut, most extensively in the intestine, as individual cells or small aggregations in both the epithelium and lamina propria. Accumulations were observed in the lamina propria but were random in their distribution. Four types of leucocyte were identified; lymphocytes, macrophages, plasma cells and granulocytes. These tissue granulocytes and a typical blood granulocyte were identified in the gut. Following oral intubation of ferritin, large macrophages containing ferritin associated with membranous vesicles were observed in the basal region of the epithelium of the intestine. Twenty-four hours after intubation, Macrophages containing ferritin were located in the lamina propria of the intestine.

Naturally occurring immunoglobulin Mantibodies toToxoplasma gondiiin Japanese populations

Varying degrees of naturally occurring immunoglobulin (Ig) M antibodies to Toxoplasma gondii were observed in almost all of adult Japanese populations negative for IgG antibodies as determined by an enzyme-linked immunosorbent assay (ELISA). The antibody activity was reduced by absorption of sera with Toxoplasma soluble antigen or by 2-mercaptoethanol treatment of the IgM fraction after sucrose density gradient centrifugation. Umbilical cord sera had almost no detectable IgM antibodies, and the ELISA value in infants increased with age until 1 year. Most paired sera collected from adults at a 1-year interval showed constant IgM antibody levels, suggesting retention of natural IgM antibodies throughout their lives without changing ELISA values of greater than or equal to 0.1/year. Polar staining was observed in immunofluorescent studies for 14 serum samples with natural IgM antibody levels of greater than or equal to 0.5, while samples obtained from a pregnant woman with natural IgM antibody levels of greater than or equal to 0.9 reacted to the whole organism as was observed in positive sera of acute patients. Western blotting analysis revealed that natural IgM antibodies were directed to multiple antigen molecules. The band pattern differed slightly from one serum to another, but almost consistent patterns were observed in sera sequentially obtained from an adult over 4 years.

Immunocytochemical typing of ABO blood groups in vaginal swabs partly contaminated with semen

ABH typing by immunocytochemical method has been carried out on 163 selected vaginal swabs. 127 cases (78%) were determined correctly, 11 cases (7%) incorrectly and 25 cases (15%) could not be classified. Often, not all of the vaginal cells showed the expected positive staining, which was not counted as a false result. The incorrect results were not dependent on the secretor status, but 37% of the non-secretor cases could not be classified immunocytochemically, as compared with 12% of the secretors. In a second series, 61 vaginal swabs, dried on microscope slides, have been covered with semen from an A1 B secretor. Absorption of heterologous antigens by the vaginal epithelia could be demonstrated only after extremely long incubation with semen and extremely long incubation with the anti-A or anti-B antibodies. From the 163 "native" swabs, 17 gave a positive reaction with the acid phosphatase test, but only one false ABH result. A possible influence of bacteria upon the results is discussed. We believe that in practice, no faults in immunocytochemical ABH typing have to be expected, due to absorption of heterologous antigens.

Anaphylaxis

Anaphylactic reactions are acute medical emergencies characterized by the abrupt onset of hemodynamic instability, respiratory distress from bronchoconstriction or laryngeal edema, urticaria, and angioedema. These clinical manifestations may occur singly or in any combination. Inciting stimuli are diverse, ranging from penicillin, Hymenoptera venom, and radiographic contrast media to exercise. The pathogenesis usually involves interaction of an antigen with specific immunoglobulin E (IgE) antibodies on the surface of mast cells or basophils, which then results in the release of chemical mediators from intracytoplasmic granules and the generation of arachidonic acid metabolites, including prostaglandin D2, and leukotrienes B4, C4, D4, and E4, at the cell membrane. Mediator release from mast cells and basophils may also be stimulated by non-IgE mechanisms, such as complement activation or direct mast cell/basophil activation. Mast cell and basophil—derived mediators have a panoply of effects, including vasodilatation, increased vascular permeability, smooth muscle contraction, airway mucous gland hypersecretion, and chemotaxis of neutrophils and eosinophils. These cellular events result in the observed clinical features. Effective treatment depends on prompt recognition of the clinical syndrome of anaphylaxis, interruption of antigen exposure and absorption when feasible, and administration of appropriate medication. Epinephrine is the drug of first choice for all of the manifestations of anaphylaxis. Adjunctive therapy with oxygen, fluid, H1 and H2 antihistamines, bronchodilators, corticosteroids, and other vasopressors is frequently necessary. Prevention of recurrence is vital. The roles of patient education, skin testing, pretreatment, and desensitization are reviewed.

Use of monoclonal antibodies against Rickettsia tsutsugamushi Kawasaki for serodiagnosis by enzyme-linked immunosorbent assay

Monoclonal antibodies (MAbs) against Rickettsia tsutsugamushi Kawasaki were prepared. The crossreactivity tests of the MAbs performed by using antigenically distinct strains of R. tsutsugamushi in immunofluorescence and immunoblotting analyses indicated that the Kawasaki strain contains a strain-specific epitope and also contains a common epitope on the 56-kDa polypeptide cross-reactive with the Gilliam strain, group- and subgroup-specific epitopes on the 46-kDa polypeptide, and a subgroup-specific epitope on the 25-kDa polypeptide. By using the strain-specific MAb for serodiagnosis of tsutsugamushi disease (or scrub typhus fever), we have established a method which was designated the inhibition enzyme-linked immunosorbent assay. The principle of the method is to measure the percentage of inhibition of antigen absorption on a MAb-coated plate by antibody-positive sample sera which were mixed with the antigen suspension. The advantages of this test for practical use are that (i) crude antigen can be used, i.e., purification of the antigen is not required; (ii) the test is more sensitive than immunofluorescence; (iii) the final judgment of plus or minus is clear-cut; and (iv) rickettsial antigenic types in the patients can be distinguished by this test.

Anaphylaxis Is Enhanced by Increased Absorption of Antigen in Postinflammatory State

Hemagglutinating antibodies and cell-mediated immunity are increased when antigens are injected intraperitoneally (i.p.) into rats during the healing phase of a chemical peritonitis. In the present work, the anaphylactogenic effects of either sensitization or challenge were increased when any of three different antigens were injected i.p. in the postinflammatory state. The postinflammatory state made it possible to sensitize rats for anaphylaxis without any adjuvants at all. Lymph nodes draining the peritoneal cavity had evidence of enhanced absorption of inoculum in the postinflammatory state.

Antigen absorption in rabbit bacterial diarrhea (RDEC-1)

Intestinal absorption of antigenic (intact) and degraded beta-lactoglobulin and horseradish peroxidase was studied in rabbits experimentally infected at weaning with the rabbit-specific Escherichia coli strain RDEC-1 (015:NM). Transepithelial fluxes of both proteins were measured at four stages after infection: early, peak, late, and recovery, on segments of ileum and Peyer's patches mounted in Ussing chambers. During this period of observation, absorption of antigenic beta-lactoglobulin and intact horseradish peroxidase decreased significantly in the ileum and Peyer's patches of age-matched controls. No significant age-related decrease was observed in the controls for the transport of these proteins in degraded form. RDEC-1 infection caused, first, a rise in degraded protein fluxes across Peyer's patches only, during the early phase of the disease. Second, during the peak phase of infection, absorption of antigenic beta-lactoglobulin by the ileum rose to 74.0 ng/hr/cm2 (90% confidence interval: 63.1, 86.8) vs 15.8 (5.8, 42.8) in the controls (P = 0.07), and absorption of intact horseradish peroxidase rose to 21.8 (16.5, 26.7) ng/hr/cm2 vs 4.4 (0.7, 26.6) in control ileum, (P = 0.09). These rises, which were similar in Peyer's patches, delayed the physiologic decrease in protein absorption that occurs with age. These results indicate that increased antigen absorption is observed during bacterial diarrhea and that it might interfere with the immune responses of the host.

Inflammation in HLA-B27-associated Diseases

The pathogenetic mechanisms in the development of spondyloarthropathies are multifactorial. These include the possible role of infective micro-organisms which can by direct invasion lead to persistence of microbial antigens and thus trigger arthritis or by cross-reactions with the host tissue lead to inflammatory symptoms or by cross-reactions with HLA-B27 trigger cytotoxic T-cell response. After the primary event, exaggerated inflammatory response can lead to amplification of inflammation. The components in the amplification of inflammation include hyperreactive neutrophils and serum factors such as enhanced production of activation products of complement in subjects with HLA-B27. The enhanced neutrophil function seems to persist in patients with previous severe inflammatory symptoms during acute reactive arthritis or in those with late inflammatory complications. The enhancement is probably caused by priming effect by lipopolysaccharide, which seems to persist for a long period in patients with acute reactive arthritis. Enhanced production of monokines can contribute to the enhanced inflammation in patients with spondyloarthropathies. The primed phagocytes can respond vigorously when rechallenged with antigenic load during a new infection, thus leading in some patients to recurrent or chronic inflammatory symptoms. Antimicrobial therapy or sulphasalazine by modifying antigen elimination or absorption can diminish inflammatory response during acute arthritis and in chronic spondyloarthropathies. Long-term follow-up studies are needed to find out whether prolonged therapies with these agents affect the prognosis of spondyloarthropathies.

Antigen absorption in bacterial diarrhea: in vivo intestinal transport of beta-lactoglobulin in rabbits infected with the entero-adherent Escherichia coli strain RDEC-1.

We studied the absorption of both antigenic and degraded beta-lactoglobulin (beta-LG) from the ileum to the portal blood, in rabbits infected at weaning with the entero-adherent Escherichia coli strain RDEC-1. The infection was characterized by high bacterial excretion from days 7 to 18 postinfection (pi), acute diarrhea for 10 days, and considerable growth retardation. Intestinal absorption of beta-LG was measured at four stages of the infection: early (day 3 pi), peak (day 10 pi), late (day 18 pi), and recovery (day 30 pi). During the 30-day period of infection, age-matched control rabbits exhibited a significant decrease in antigenic and degraded beta-LG absorption. In both control and infected animals, more than 90% of the beta-LG was absorbed by a degrading pathway and the remainder in antigenic form by a minor pathway. RDEC-1 infection significantly raised antigenic beta-LG absorption from days 10 to 30 pi, which delayed the decrease that normally occurs with age. Degraded beta-LG absorption was not modified by the infection, except for a slight increase observed at the recovery stage (day 30 pi). These results suggest that RDEC-1 diarrhea increases absorption of food antigens. The subsequent local or systemic immune responses are not known, but pathologic consequences are possible in susceptible individuals.

INCREASED ANTICEN ABSOBPTIN INDUCED BY INFECTION WITH THE ADHERENT ENTEROPATHOCENIC E.COLI STRAIN RDEC-1 IN RABBIT ILEUH AND PEYER'S PATCHES

Intestinal absorption of antigenic (intact) and degraded β-lacto-globulin (β-lg) and horseradish perioxidase (HRP) was studied in rabbits experimentally infected at weaning with the rabbit-specific Escherichia coli strain RDEC-1 (015: NM). Traneptithelial fluxes of both proteins were measured at four stages post infection: early, peak, late and recovery, on segments of ileum and Peyer's patches mounted in Ussing chambers. During this period of observation, absorption of antigenic β-lg and intact HRP decreased significantly in the ileum and Peyer's patches of age-matched controls probably reflecting gut closure to the food antigen. No significant age-related decrease was observed in the controls for the transport of these proteins in degraded form. During the early phase of RDEC-1 infection, absorption of egraded protein fluxes rose across Peyer's patches only. During the peak phase of infection, absorption of antigenic β-lg (74.0 ng/h.cm2) and intact HRP (21.8 ng/h cm2) rose fivefold compared to controls (15.8 and 4.4 ng/h.cm2 respectively). These rises, which were also found in Peyer's patches, delayed the physiologic decrease in protein absorption which occurs with age. These results indicate that increased antigen absorption is observed during RDEC-1 bacterial diarrhea, and that it might interfere with the immune responses of the host.

The appearance of soluble antigen, horseradish peroxidase (HRP), in tissues of the rainbow trout ( Salmo gairdneri Richardson), subsequent to variable dip-immersion procedures

There currently exists a paucity of information regarding the quantitative absorption of soluble protein antigens by fish subsequent to immersion. Accordingly, a series of experiments was undertaken in order to determine the tissue localization of horseradish peroxidase (HRP) in juvenile rainbow trout, following variable periods of immersion (10–60 s) in a bath containing 2.5 mg HRP mg −1. In addition, the time-course of appearance and net tissue accumulation of HRP was examined. Regardless of immersion period HRP was detectable within all tissues examined as early as 5 min post-treatment. Peak net tissue accumulation of HRP on a per g wet weight basis was found to be of the order spleen>kidney>heart>liver. Peak tissue levels of HRP were recorded following 60-s exposure to the antigen.

Absorption of food protein antigen in infants with food protein-induced enterocolitis.

Increased gastrointestinal absorption of intact antigen with systemic immunization has been considered a major etiologic factor in the development of food sensitivity. We attempted to test this hypothesis in infants with suspected food protein-induced entercolitis by measuring serum ovalbumin (OVA) concentrations after ingestion of egg white (prior to the performance of good challenges to establish this diagnosis). We first noted significant underestimation of serum OVA concentrations in the presence of even low serum anti-OVA antibody concentrations (greater than 1:12). Next, using selected noninhibitory sera, we found that all infants studied absorbed some OVA, there was no correlation between serum OVA levels and age (3-11 months), and there was no significant difference between serum OVA concentrations in infants who subsequently had positive oral food challenge responses (120 +/- 67 ng/ml) and a matched group with negative challenges (102 +/- 80). These data do not support the hypothesis that "intestinal closure" (antigen exclusion) occurs in the neonatal period or the role of antigen absorption as the major etiological factor in the development of food sensitivity. Better methods of quantitating macromolecular absorption must be developed before the role of antigen absorption in food sensitivity can be assessed. Of note, urinary excretion of intact OVA also occurred. This varied greatly from one voiding to the next and continuing for at least 13 hr after ingestion.

TRICHOPHYTON ASTHMA: SENSITISATION OF BRONCHI AND UPPER AIRWAYS TO DERMATOPHYTE ANTIGEN

12 adult patients with perennial asthma and chronic skin infection were found to have immediate hypersensitivity to Trichophyton spp. 10 patients were tested by bronchial provocation and gave immediate bronchial reactions to an extract of T tonsurans. Double-blind, placebo-controlled nasal challenge of 8 patients demonstrated that the upper airways of these patients were also sensitive to this dermatophyte antigen. In addition to perennial asthma most of the patients had persistent eosinophilia and chronic rhinosinusitis. The results suggest that absorption of fungal antigen can give rise to IgE antibody production, sensitisation of the airways, and symptomatic asthma and rhinosinusitis. Several patients had many of the features of late onset or "intrinsic" asthma.