Serum antibodies to dietary antigens: a prospective study of the diagnostic usefulness in celiac disease of children

We examined 1,541 consecutive serum samples from 707 children with suspected food intolerance and 32 with treated celiac disease (CD) for IgG and IgA antibody reactivities to antigens from gluten, egg, and cow's milk by an enzyme-linked immunosorbent assay (ELISA). Samples from 72 patients showed increased IgA and/or IgG reactivity to gluten antigens; four were known CD patients not complying with a gluten-free diet, 13 were suspected CD patients challenged with gluten, and 30 most likely had CD as suggested by small intestinal villous atrophy and histological and/or clinical improvement on a gluten-free diet. The remainder with increased antigluten activity had other disorders that might have affected mucosal permeability. Nevertheless, the median IgA reactivity to gluten was significantly higher in the CD group, and the probability for CD increased from 25 to 100% when this reactivity was above 2.4 optical density (OD) units in our ELISA. Sixteen CD patients (but none of those without CD) had IgA reactivity to gluten higher than 2.4 OD units. We conclude that ELISA determinations of levels of serum antibodies reacting to dietary antigens is a valuable adjunct in the diagnosis of CD in children.     

A prospective study of humoral immune responses to cow milk antigens in the first year of life

Previous studies have shown that in cow milk allergy the specific immune response to dietary cow milk antigens is deficient. This study aimed at delineating the development of humoral immune response to cow milk antigens in healthy infants. Twenty-five healthy newborns were enrolled, and seen at scheduled visits at the ages of three, six and eleven months, and they formed two groups: those breastfed and those fed adapted cow milk formulae. The local immune response in the gut was approximated using the ELISPOT assay of circulating antibody secreting cells. At the age of three months, in the formula fed group, cells secreting specific IgA to cow milk antigens were detected despite low levels of IgA serum antibodies. The total number of IgA secreting cells increased with age (p = 0.001). The milk in the infant diet directly influenced this development so that the age related increase was significantly greater in the formula fed group (p = 0.04). The results indicate that diet has a significant effect on the developing immune system, and that healthy infants are able to respond in an antigen specific fashion to dietary antigens, which may be central in attaining clinical tolerance of such antigens.     

Variable increases of IgG and IgM antibodies in milk of IgA deficient women

Serum, milk and saliva from seven IgA deficient mothers were studied for the presence of IgA, IgG and IgM antibodies to Escherichia coli and polio virus antigens. Different variable patterns were obtained. One mother had very much increased IgM and IgG antibodies in milk and saliva against both antigens; the milk IgG antibodies were 11–14 times higher than the reference milk pool. Another mother showed also striking increases of both IgM and IgG antibodies in milk, as well as in saliva where the increases were much higher for the poliovirus than the E. coli antibodies. Yet another mother showed a certain increase of IgM but not of IgG antibodies in the milk. The uneven appearance of IgG and IgM antibodies in serum and secretions suggests local production. So do the differences ot antibody avidities, the variations in IgG subclass distribution of antibodies and different patterns after isoelectric focusing (IEF) /immunoblotting analysis of antibody spec-trotypes in secretions and serum.
The study illustrates the variable patterns of compensatory increases of IgG and IgM antibodies which may occur in IgA deficiency. It also shows that the milk from IgA deficient mothers can still be rich in antibodies, in spite of the lack of secretory IgA.     

High levels of IgA in HIV-1-perinatally-infected children. Antigen specificity and possible role of increased substance P plasma levels

The specificity of IgA against food, inhalant, bacterial and fungine antigens as well as for HIV-1 proteins was investigated in 14 HIV-1-infected children (CDC stage P-2) and 15 controls. IgA against food- and inhalant antigens as well as against tetanus toxoid were significantly more often present in the HIV positive children than in controls. No difference between the two groups was present for IgA against Candida albicans. A significant increase of substance P, a strong IgA synthesis inducing neuropeptide, was demonstrated in the plasma of HIV-1 infected children. In conclusion, high levels of IgA seem to reflect a complex immune dys-function in which many factors are involved. The importance of neuro-immune dysregulation is discussed.     

Serum and salivary antibody responses to non-capsular Haemophilus influenzae antigens in children with meningitis and epiglottitis

Serum IgG, IgA and IgM antibody and salivary IgA antibody concentrations to non-capsular Haemophilus influenzae antigens were measured in 13 children with H. influenzae type b meningitis and in 15 children with epiglottitis. Most had detectable serum IgG and IgM antibody at presentation but significantly fewer patients with meningitis had serum IgA antibody at presentation ( P <0.05). Serum antibody concentrations had risen significantly by 3 weeks after presentation in patients with epiglottitis only. Convalescent serum IgG antibody concentrations against these antigens were higher in younger children with epiglottitis.
Salivary IgA antibody to H. influenzae was detectable at presentation in all children with epiglottitis and in 12 of 13 with meningitis. Salivary antibody concentrations did not differ significantly between the two patient groups at presentation, although patients with meningitis had higher salivary IgA antibody concentrations than 10 children of similar age with bronchiolitis ( P <0.02). There was no association between the presence of salivary antibody and low concentrations of convalescent serum antibody.
The rise in convalescent serum antibody concentrations to non-capsular H. influenzae antigens only in children with epiglottitis is similar to findings for antibody to capsular polysaccharide. However, this rise was greater for IgG in younger patients, and the low titre of convalescent serum antibody in patients with meningitis was not associated with higher titres of IgA antibody in secretions as described by others for polysaccharide antibody. These findings suggest that the poor serum antibody response to these antigens in patients with meningitis is independent of age and is not due to mucosal induction of systemic tolerance.     

Serum and salivary antibody responses to non-capsular Haemophilus influenzae antigens in children with meningitis and epiglottitis

Serum IgG, IgA and IgM antibody and salivary IgA antibody concentrations to non-capsular Haemophilus influenzae antigens were measured in 13 children with H. influenzae type b meningitis and in 15 children with epiglottitis. Most had detectable serum IgG and IgM antibody at presentation but significantly fewer patients with meningitis had serum IgA antibody at presentation (P less than 0.05). Serum antibody concentrations had risen significantly by 3 weeks after presentation in patients with epiglottitis only. Convalescent serum IgG antibody concentrations against these antigens were higher in younger children with epiglottitis. Salivary IgA antibody to H. influenzae was detectable at presentation in all children with epiglottitis and in 12 of 13 with meningitis. Salivary antibody concentrations did not differ significantly between the two patient groups at presentation, although patients with meningitis had higher salivary IgA antibody concentrations than 10 children of similar age with bronchiolitis (P less than 0.02). There was no association between the presence of salivary antibody and low concentrations of convalescent serum antibody. The rise in convalescent serum antibody concentrations to non-capsular H. influenzae antigens only in children with epiglottitis is similar to findings for antibody to capsular polysaccharide. However, this rise was greater for IgG in younger patients, and the low titre of convalescent serum antibody in patients with meningitis was not associated with higher titres of IgA antibody in secretions as described by others for polysaccharide antibody. These findings suggest that the poor serum antibody response to these antigens in patients with meningitis is independent of age and is not due to mucosal induction of systemic tolerance.(ABSTRACT TRUNCATED AT 250 WORDS)     

The high lectin-binding capacity of human secretory IgA protects nonspecifically mucosae against environmental antigens

The anti-infectious role of human milk may be, at least partly, ascribed to its content in secretory IgA. As lectins are present in various infectious antigens, the binding of different types of IgA to three lectins (concanavalin A, peanut agglutinin, wheat germ agglutinin) was studied by Elisa. The specificity of those bindings was assessed by inhibitory experiments performed with the corresponding oligosaccharides. The following were found for the three lectins: (1) the lectin-binding capacity of colostrum secretory IgA was markedly greater than that of normal plasma IgA1 (p less than 0.001); (2) the lectin-binding capacity of polymeric IgA1 was greater than that of monomeric IgA1 (p less than 0.001). This property of mucosal IgA may be responsible of a nonimmune opsonization able to prevent the early step of some infectious mucosal diseases, i.e. the attachment of bacteria to epithelial cells by lectin-like bonds and also the penetration into the body of some antigens able to favor the development of allergy. Milk mucosal IgA, present in significant amounts in human colostrum and mature milk - but not in infant formulas - may therefore play an important polyvalent protective role in newborns.     

Concentration of milk secretory immunoglobulin A against Shigella virulence plasmid-associated antigens as a predictor of symptom status in Shigella-infected breast-fed infants.

We conducted a prospective, community-based study of healthy breast-fed Mexican infants to determine the protective effects of anti-Shigella secretory IgA antibodies in milk. Milk samples were collected monthly, and stool culture specimens were obtained weekly and at the time of episodes of diarrhea. Nineteen breast-fed infants were found to have Shigella flexneri, Shigella boydii, or Shigella sonnei in stool samples. Ages of the 10 infants with symptomatic infection and the nine with asymptomatic infection did not differ significantly. Milk samples collected up to 12 weeks before infection were evaluated by enzyme-linked immunosorbent assay for secretory IgA antibodies against lipopolysaccharides of S. flexneri, S. boydii serotype 2, S. sonnei, and virulence plasmid-associated antigens. The geometric mean titers of anti-Shigella antibodies to virulence plasmid-associated antigens in milk received before infection were eightfold higher in infants who remained well than in those in whom diarrhea developed. The significance of milk secretory IgA directed against lipopolysaccharide was less clear. We conclude that human milk protects infants against symptomatic shigella infection when it contains high concentrations of secretory IgA against virulence plasmid-associated antigens.     

Antibodies to pertussis antigens in pediatric health care workers

BACKGROUND: To compare the antibody concentrations against Bordetella antigens in health care workers in a pediatric hospital with those of two different populations without professional contact with children. METHODS: In a pediatric hospital 155 health care workers (135 female, 20 male), 292 male navy recruits after 3 months at sea and 146 regular blood donors (41 female, 105 male) were screened for antibodies of isotypes IgG and IgA to pertussis toxin (PT) and filamentous hemagglutinin (FHA) by enzyme-linked immunosorbent assay. RESULTS: Pediatric health care workers were positive for IgG anti-PT in 88%, for IgA anti-PT in 52%, for IgG anti-FHA in 99% and for IgA anti-FRA in 84%. Relative numbers for blood donors and recruits were 86 and 80% for IgG anti-PT, 56 and 55% for IgA anti-PT, 100 and 98% for IgG anti-FHA and 92 and 82% for IgA anti-FHA, respectively. Reverse cumulative distribution of all antibodies except for IgA anti-FHA showed no differences among the three groups; 2% of pediatric personnel, 3% of blood donors and 3% of navy recruits, respectively, had IgG anti-PT > or = 100 enzyme-linked immunosorbent assay units/ml, indicating a recent contact to Bordetella pertussis. CONCLUSION: Antibodies to B. pertussis antigens, such as IgG/IgA anti-PT and IgG/IgA anti-FHA, were similarly distributed in all three groups. Our results suggest that exposures leading to measurable immune responses to pertussis antigens in German pediatric health care workers are not significantly more frequent than in other populations without professional contacts with children.     

Protection against Campylobacter diarrhea: role of milk IgA antibodies against bacterial surface antigens

In developing countries, Campylobacter jejuni causes diarrhea and dysentery, especially in children less than one year of age. Breast feeding protects against infectious diarrhea, with milk IgA antibody playing a determining role. Therefore, it has been proposed to increase the protective effect of human milk by vaccinating women of child-bearing age. To identify antigens which may induce protective breast-milk IgA, we analyzed 60 strains of C. jejuni isolated from asymptomatically- and symptomati-cally-infected breast-fed children less than 12 months of age. Surface antigens of c. jejuni , separated by polyacrylamide gel electrophoresis, were probed with breast milk collected concurrently with the fecal sample from which C. jejuni was isolated, and specific IgA was developed by immunoblotting. Our results indicate that milk antibodies against three high molecular weight bacterial surface antigens of 95, 110 and 185 kDa are involved in protection of infants infected with C. jejuni (p = 0.00964 for one-tailed Fisher's cxact test).     

Protection against Campylobacter diarrhea: role of milk IgA antibodies against bacterial surface antigens

In developing countries, Campylobacter jejuni causes diarrhea and dysentery, especially in children less than one year of age. Breast feeding protects against infectious diarrhea, with milk IgA antibody playing a determining role. Therefore, it has been proposed to increase the protective effect of human milk by vaccinating women of child-bearing age. To identify antigens which may induce protective breast-milk IgA, we analyzed 60 strains of C. jejuni isolated from asymptomatically- and symptomati-cally-infected breast-fed children less than 12 months of age. Surface antigens of c. jejuni , separated by polyacrylamide gel electrophoresis, were probed with breast milk collected concurrently with the fecal sample from which C. jejuni was isolated, and specific IgA was developed by immunoblotting. Our results indicate that milk antibodies against three high molecular weight bacterial surface antigens of 95, 110 and 185 kDa are involved in protection of infants infected with C. jejuni (p = 0.00964 for one-tailed Fisher's cxact test).     

Titres of specific antibodies to poliovirus type 3 and tetanus toxoid in saliva and serum of children with recurrent upper respiratory tract infections

A study of antibody levels (in saliva and blood) against common vaccine antigens was performed in a population of 32 children suffering from recurrent upper respiratory tract infections (URTI). None of the patients had primary or secondary immunodeficiency syndromes or other known predisposing factors for respiratory diseases. Titres of the isotype-specific antibodies immunoglobulin A (IgA), immunoglobulin M (IgM), and immunoglobulin G (IgG) against two vaccine antigens – poliovirus type 3 (P3) and tetanus toxoid (TT), a viral antigen and a bacterial antigen, respectively – were measured in unstimulated saliva and serum, both in patients and in 24 healthy children (controls), by using a standard enzyme-linked immunosorbent assay (ELISA). In addition, levels of total IgA and avidity of IgA antibodies to both P3 and TT in saliva were evaluated. No difference was found between patients and controls as to levels of total IgA, or specific IgA and IgM antibodies against both P3 and TT in saliva. Furthermore, the avidity of salivary IgA antibodies against the two antigens did not differ between the two populations. However, the average concentrations of saliva-specific IgG antibodies to both the viral and the bacterial antigen were significantly lower (p < 0.01 for P3 and p < 0.05 for TT, respectively) in saliva of children with recurrent URTI, whereas no difference was found in serum for any immunoglobulin isotype determined compared with healthy individuals. The results of the present study provide suggestive evidence for the existence of subtle IgG-restricted defects in antibody responses at the mucosal level, but not at the serum level, in some children with undue susceptibility to URTI.     

Enhanced fecal excretion of selected immune factors in very low birth weight infants fed fortified human milk

The amounts of lactoferrin, lysozyme, total IgA, secretory IgA (SIgA), and specific SIgA antibodies to a pool of Escherichia coli O antigens were measured in 96-h collections of feces obtained from 28 very low birth weight infants, 28-30 wk of gestation, studied at 2.5 and 6 wk of age. Eighteen of these infants were fed their mothers' milk fortified with fractions of skim and cream derived from pasteurized, lyophilized, mature human milk (FM) and 10 infants were fed commercial cow's milk-based formula. The concentrations of these selected immune factors in the FM and formula also were measured. Specific SIgA antibodies to E. coli O antigens were detected in the feces of 90% of the FM-fed infants, but in none of the feces of the formula-fed infants. The feces obtained from FM-fed infants had markedly greater quantities of lactoferrin (p less than 0.001), lysozyme (p = 0.006), and IgA (p less than 0.001) than those of cow's milk formula-fed infants. The concentrations of total and secretory IgA were correlated significantly (r = 0.88, p less than 0.001) and 95% of total IgA was SIgA. The fecal concentration of specific SIgA antibodies to E. coli O antigens in FM-fed infants correlated with the concentration of these antibodies in their milk (p less than 0.001). However, there were no direct relationships between the milk concentrations or the infant's intakes of the other selected immune factors and the excretion of these factors in the feces.(ABSTRACT TRUNCATED AT 250 WORDS)     

ESCHERICHIA COLI O ANTIBODY CONTENT IN MILK FROM HEALTHY SWEDISH MOTHERS AND MOTHERS FROM A VERY LOW SOCIO-ECONOMIC GROUP OF A DEVELOPING COUNTRY

Abstract. The antibody content of milk from healthy Swedish mothers was compared with that of milk from mothers of a very low socio-economic group in a developing country. Antibodies of various immunoglobulin classes against E. coti O antigens were determined with the enzyme-linked immunosorbent assay (ELISA). The milk antibodies which mainly belonged to the secretory IgA class appeared in similar concentrations in milk from the two groups using E. coli antigens of Swedish as well as Pakistani origin. The secretory IgA antibodies could be demonstrated in the stool of the breast-fed infants of the undernourished mothers. Also the concentration of serum IgG and IgA antibodies to E. coli O antigens were similar in the Pakistani and Swedish mothers. The serum IgM antibody levels of the Pakistani mothers were higher, however, presumably due to a higher frequency of infections. It was noted that the milk production decreased considerably upon the hospitalization of the healthy and well-to-do Swedish mothers. The small milk volumes of the undernourished Pakistani mothers suggest that the lactation failure observed was mainly due to inadequate milk flow and not to decreased milk quality. The results indicate the necessity of studying the nutritional, psychological and social factors responsible for low milk yield and add yet another reason to stimulate prolonged breastfeeding.     

THE DEVELOPMENT OF MAMMARY SECRETORY IMMUNITY IN THE HUMAN NEWBORN

ABSTRACT. Yap, P. L., McKiernan, J., Mirtle, C. L. and McClelland, D. B. L. (MRC Unit of Reproductive Biology, 37 Chalmers Street, Edinburgh; University of Nottingham Department of Child Health; University of Edinburgh Department of Therapeutics and Clinical Pharmacology and the Blood Transfusion Service, Royal Infirmary, Edinburgh, Scotland). The development of mammary secretory immunity in the human newborn. Acta Paediatr Scand, 70:459,.–Milk protein concentrations were determined either by radioimmunoassay (IgA and IgG) or single radial immunodiffusion (IgM, lactoferrin, albumin and lysozyme) in single or serial samples of neonatal milk (witch's milk) obtained from 33 healthy newborns (seven of whom were light for dates), four ill newborns following major surgery and four newborns suffering from one of a variety of infections. In addition, paired neonatal milk and heel prick blood samples were collected from seven newborns, and paired neonatal milk and maternal milk samples were collected from a further seven neonates and their respective mothers. The concentrations of secretory IgA (11S IgA) in neonatal milk, although 300-fold lower than the corresponding IgA concentrations in maternal milk, when compared with neonatal serum IgA concentrations, were crfnsistent with local synthesis of IgA occurring in the neonatal mammary gland. Among the milk proteins studied, only 11S IgA concentrations increased significantly after birth in neonatal milk, the rise being unrelated to the gestational age of the newborn. As an entero-mammary circulation of IgA precursor lymphocytes exists in adults, it is suggested that the entry of foreign antigens into the neonatal gut after birth may be an important factor influencing the development of neonatal secretory immunity.     

Serum IgA antibodies against Pseudomonas aeruginosa in cystic fibrosis.

Serum IgA antibodies to Pseudomonas aeruginosa cell surface antigens were estimated by ELISA. Titres in patients with and without cystic fibrosis and with no pseudomonal infection were low (less than 105 to less than 261). Titres in patients with cystic fibrosis who were chronically infected with P aeruginosa were very high (1200-163,000), and patients who grew the organism intermittently had intermediate titres. Longitudinal studies suggested increasing tissue invasion or involvement of the lower respiratory tract, or both, with increasing time of infection and identified patients with a good prognosis after the onset of pseudomonal infection. Detection of an increased serum IgA titre can give an earlier indication than measurement of the serum IgG titre of the presence of P aeruginosa in the respiratory tract in a proportion of patients. IgA measurement seems to be better than IgG measurement at predicting the reappearance of P aeruginosa after apparent eradication of early infection. These results suggest that this assay may be a valuable additional indicator of the presence of P aeruginosa at the beginning of infection, and of the reappearance of the organism after treatment in the early stages of infection.     

Detection of IgA and IgG but not IgE antibody to respiratory syncytial virus in nasal washes and sera from infants with wheezing

BACKGROUND AND OBJECTIVE: The capacity of respiratory syncytial virus (RSV) to stimulate an IgE antibody response and enhance the development of atopy and asthma remains controversial. Nasal washes and sera from 40 infants (20 with wheezing, 9 with rhinitis, and 11 without respiratory tract symptoms) were obtained to measure IgE, IgA, and IgG antibody to the immunodominant, F and G, virion proteins from RSV. STUDY DESIGN: Children (aged 6 weeks to 2 years) were enrolled in the emergency department during the mid-winter months and seen at follow-up when they were asymptomatic. All nasal washes were tested for RSV antigen. Determinations of antibody isotypes (IgE, IgA, and IgG) to RSV antigens were done in nasal washes and sera by using an enzyme-linked immunosorbent assay. In a subset of nasal washes, IgE to RSV was also evaluated by using a monoclonal anti-F(c)E antibody-based assay. RESULTS: Fifteen patients with wheezing, two with rhinitis, and one control subject tested positive for RSV antigen at enrollment. Thirteen patients with wheezing were <6 months old, and most (77%) were experiencing their first attack. Among the children with positive test results for RSV antigen, an increase in both nasal wash and serum IgA antibody to RSV-F(a) and G(a) was observed at the follow-up visit. However, there was no evidence for an IgE antibody response to either antigen. CONCLUSION: Both IgA and IgG antibodies to the immunodominant RSV-F(a) and G(a) antigens were readily detected in the nasal washes and sera from patients in this study. We were unable to demonstrate specific IgE antibody to these antigens and conclude that the production of IgE as a manifestation of a T(H)2 lymphocyte response to RSV is unlikely.     

Inhibition of enteroaggregative Escherichia coli adhesion to HEp-2 cells by secretory immunoglobulin A from human colostrum

BACKGROUND: Enteroaggregative Escherichia coli (EAEC) is an important agent of the persistent diarrhea among low socioeconomic level children in developing countries that may be associated with chronic undernourishment. Breast-feeding is effective in protecting infants against diarrhea and other infectious diseases. The aim of the study is to verify the ability of human colostrum to inhibit aggregative adhesion of EAEC to HEp-2 cells and the presence of antibodies reactive to antigenic fractions of EAEC in colostrum samples. METHODS: Enzyme-linked immunosorbent assay, immunoblotting and adhesion assays of EAEC to HEp-2 cells were done with pooled or individual colostrum samples (n = 35). Assays were performed with a well-known EAEC strain, 044:H18 E. coli (strain 042). Colostral IgA was isolated by affinity chromatography in Sepharose anti-human alpha chain column. RESULTS: Total colostrum and isolated IgA inhibited EAEC adhesion, and this ability was associated with the presence of IgA antibodies against a 15-kDa band, compatible with the subunits of aggregative adherence fimbrial adhesin II, characteristic of the 042 strain, absent in its plasmid-cured isogenic strain, that was used as control. Individual colostrum samples also inhibited adhesion, showed variable antibody titles against EAEC antigens in enzyme-linked immunosorbent assay and recognized many antigenic fractions in immunoblotting assays, including the 15-kDa band. CONCLUSIONS: These results confirm that IgA from human colostrum inhibits adhesion of EAEC to HEp-2 cells and suggest that colostrum IgA antibodies reactive to EAEC antigens may play a role in protection of infants against diarrhea caused by these bacteria.     

Local immune response in patients with cow milk allergy: follow-up of patients retaining allergy or becoming tolerant.

To assist in identifying factors that determine the clinical outcome of cow milk allergy, we subjected to rechallenge 37 patients with a history of cow milk allergy, mean (+/- SD) age 27.6 +/- 7.1 months, after a follow-up of 13.5 +/- 5.1 months with a milk-free diet. A solid-phase enzyme-linked immunoassay was used to assess the total number of immunoglobulin-secreting and specific antibody-secreting cells among peripheral blood lymphocytes primed during provocation by milk antigens, giving indirect evidence of local immune response in the gut. Patients with persistent cow milk allergy (n = 13) had milder reactions at rechallenge than they had shown at the time of diagnosis. Numbers of immunoglobulin-secreting cells in these patients increased significantly from a geometric mean (95% confidence interval) in the IgA class of 1570 (1009, 2445) to 2984 (1941, 4583) IgA-secreting cells/10(6) cells, in the IgG class of 1445 (1067, 1959) to 2740 (1698, 4425) IgG-secreting cells/10(6) cells, and in the IgM class of 842 (534, 1325) to 2235 (1429, 3495) IgM-secreting cells/10(6) cells. By contrast, in patients (n = 24) who had acquired cow milk tolerance, the number of immunoglobulin-secreting cells did not increase during provocation. The total number of IgA-secreting cells before rechallenge was significantly higher than it had been before the initial challenge. The patients who acquired cow milk tolerance also had specific antibody-secreting cells of IgA isotype before the second challenge. These results indicate that in cow milk allergy the ability to mount a local immune response against cow milk antigens, particularly in the IgA class, is related to the suppression of clinical sensitivity.     

Mucosal immunity and strategies for novel microbial vaccines

Infectious diseases continue to be the leading cause of morbidity and mortality worldwide. Increased awareness of the fact that mucosal membranes are the most frequent portals of entry of pathogenic microorganisms has prompted studies aimed at the development of vaccination protocols and antigen delivery systems that would lead to an increased protection of mucosae. Although systemic and strictly local immunizations are of limited effectiveness in the induction of mucosal protection, ingestion or inhalation of antigens results in a generalized immune response manifested by the appearance of specific antibodies of the secretory immunoglobulin (Ig) isotype in external secretions due to the dissemination of IgA precursor cells from IgA-inductive lymphoid tissues. Furthermore, additional inductive sites strategically positioned at the opening of the respiratory and digestive tracts may also be suitable targets for induction of immune responses at desired effector sites. To prevent degradation and the increase of ingested antigens absorption, novel strategies including enclosure of antigens into biodegradable microspheres, liposomes or their expression in viral and bacterial vectors and plants are currently being considered. Forthcoming technological advances in antigen preparation and routes of delivery will undoubtedly have a profound impact on immunization practices in the future.