Major Portal Of Entry Research Articles

Immunostimulatory-sequence DNA is an effective mucosal adjuvant.

The respiratory, gastrointestinal, vaginal, and rectal mucosa are major portals of entry for infectious agents and foreign proteins (Czerkinsky and Holmgren 1995; Staats and McGhee 1996). Locally produced and secreted immunoglobulin A (IgA) and cytotoxic T lymphocytes (CTL) within the mucosal tissue and draining lymph nodes protect against microbial infection (Gallichan et al. 1993; Czerkinsky and Holmgren 1995; Staats and McGhee 1996; Ada and McElrath 1997). Because the mucosal immune system serves a front-line role in protecting us from our environment, there is a great deal of interest in developing strategies for stimulating protective mucosal immune responses. Unfortunately, traditional vaccination methods are not effective and, at present, there is no simple, safe, and generally applicable approach for the induction of mucosal immune responses.

Molecular cloning, expression, localisation and functional characterisation of a rabbit SULT1C2 sulfotransferase

The importance of sulfotransferases in xenobiotic metabolism is gaining recognition. The gastrointestinal (GI) tract is a major portal of entry for many xenobiotics, yet little is known about the contribution of sulfotransferases to detoxication or bioactivation metabolism in these tissues. To this end, isolation and characterisation of sulfotransferases expressed in the stomach of rabbits was undertaken. A unique sulfotransferase cDNA (GenBank Accession No. AF026304) was isolated from a rabbit stomach cDNA library. This cDNA was 1439 base pairs (bp) long and has an open reading frame of 888 bp. On expression of the cDNA in both COS cells and E. coli, a protein molecular weight of 34 kDa was detected on SDS-PAGE. Immunoblotting using an antibody raised in goats against the bacterially expressed protein detected expression of the protein in GI tract tissues. The 34 kDa immunoreactive band was detected in rabbit GI tract tissues (stomach, duodenum, jejunum, ileum, colon, caecum and rectum), liver and kidneys, but not in the lungs ( n=3). The human ortholog (GenBank Accession No AF026303) of the rabbit enzyme was cloned from a human stomach cDNA library. These two enzymes share 84% amino acid sequence identity and have been termed 1C2 sulfotransferases. When functional and kinetic characterisation of the recombinant rabbit and human proteins was carried out using 16 known ST substrates, detectable sulfonation activity was observed only with p-nitrophenol (with K m values of 2.2 mM and 13.3 mM, respectively). In conclusion, we have identified a rabbit GI tract sulfotransferase belonging to a newly defined sulfotransferase subfamily.

Glucose absorption and utilization by rat embryos.

There is little doubt that glucose plays a significant nutritional role in early somite embryos. The high glucose utilization of anaerobic glycolysis drops as the activity of the Kreb's cycle and terminal electron transport increase. Concurrently, maturation of mitochondrial cristae and dependence on oxygen supply are taking place. The neuroepithelium of the early somite rat embryo responds in vitro during culture by microvilliar lengthening when exposed to glucose levels of 50 mg/dl or more. At lower glucose concentrations both in whole embryo culture and inside the closed neural tube the microvilli are shorter. Lengthening of the microvilli at room temperature is produced only by d-glucose and 2-deoxyglucose, two hexoses that are absorbed and phosphorylated. Cytochalasin D which disrupts actin polymerization causes ballooning of the microvilli. A role of this microvillar elongation in degenerative changes seen in uncontrolled diabetes and on function of the immune system is proposed. The amniotic cavity is one major portal of entry for glucose during the early somite embryo stage. The 7-fold increase in volume of the amniotic cavity after day 10 allows the rat embryo to convert its axis from dorsal to ventral flexion.

CDNA Cloning, Heterologous Expression, and Characterization of Rat Intestinal CYP2J4

The small intestine is the major portal of entry of ingested xenobiotics. Previous studies from this and other laboratories indicated that at least 6 of the 33 xenobiotic metabolizing forms of P450 currently identified are expressed in rat small intestinal epithelial cells. In the present study, a previously unidentified rat P450, designated CYP2J4, was identified in rat small intestine using PCR. The full-length CYP2J4 cDNA contains an open reading frame for a protein of 501 residues and is 72.5 and 75.8% identical to rabbit CYP2J1 and human CYP2J2, respectively, in deduced amino acid sequences. The coding region of CYP2J4 cDNA has been cloned into a baculoviral expression vector (pVL1392) and expressed in culturedSpodoptera frugiperta(SF9) cells. The heterologously expressed CYP2J4 protein displayed a typical P450 CO-difference spectrum, with maximum absorbance at 449 nm. When purified to near electrophoretic homogeneity, it was active toward arachidonic acid in a reconstituted system with NADPH-P450 reductase and phospholipid, producing both hydroxyeicosatetraenoic and epoxyeicosatrienoic acids. RNA blot analysis with CYP2J4 cDNA as a probe detected two mRNA species, about 2.0 and 2.4 kb, respectively, in RNA preparations from liver, intestine, olfactory mucosa, kidney, heart, and lung. The 2.0-kb mRNA species was abundant in liver, small intestine, and olfactory mucosa, whereas the 2.4-kb mRNA species was predominant only in the olfactory mucosa. Immunoblot analysis of microsomal fractions from different rat tissues with a polyclonal anti-peptide antibody to CYP2J4 detected a protein with the same electrophoretic mobility as purified CYP2J4 most abundantly in small intestine and to a lesser extent in liver and other immunoreactive proteins with slightly higher electrophorectic mobility than purified CYP2J4 in a number of tissues, including small intestine, liver, kidney, lung, and olfactory mucosa. The predominant distribution of CYP2J4, which has activity toward arachidonic acid, is provocative, but its physiological function is as yet unknown.

Incidence and severity of group A streptococcal bacteremia in a medical center in Israel, 1981-1994.

To determine recent trends in the incidence and severity, group A streptococcal (GAS) bacteremia was studied over the last 14 years (1981-1994). There were 116 events of GAS bacteremia, representing 1.7% of all bacteremic episodes, without an increase in recent years. A total of 108 patients were available for study. Underlying conditions were found in 95 patients (88%), including mainly malignant diseases, chronic obstructive pulmonary disease, congestive heart failure and diabetes mellitus. A source of the bacteremia was noted in 71 patients (66%), with skin and soft tissue infection being the major portal of entry. All isolates were susceptible to penicillin. Overall mortality was 21%. Mortality had not increased in recent years, but depended significantly on several clinical factors: increased age; admission temperature; source of bacteremia (highest for GAS bacteremia without an identified source); and underlying conditions (highest for diabetes mellitus and chronic pulmonary disease, absent for patients with no underlying disease). This study shows that neither the incidence nor the severity of GAS bacteremia has increased in recent years. Severity is significantly affected by the source of bacteremia and the presence of underlying conditions.

Thoracic mycoses from endemic fungi: radiologic-pathologic correlation.

The endemic fungi Histoplasma capsulatum, Blastomyces dermatitidis, and Coccidioides immitis are primary human pathogens whose major portal of entry is the respiratory tract. Their clinical manifestations are categorized as acute, chronic or chronic progressive, or disseminated fungal disease. Most acute pulmonary infections are self-limited, and many are asymptomatic. Chronic, progressive, or disseminated disease is much less common and most often occurs in immunocompromised patients. The radiologic manifestations of these disorders are protean. They include interstitial or air-space opacities, solitary or multiple pulmonary nodules, parenchymal masses, cavities, and hilar or mediastinal adenopathy. The diagnosis of a thoracic mycosis requires familiarity with the epidemiology of the fungus in question, the various modes of clinical presentation, and the full spectrum of radiologic manifestations. Although skin and serologic tests can be useful, definitive diagnosis requires culture of the fungus from infected tissue or demonstration of the organism at microscopic examination.

Decrease of nosocomial bacteremia and nosocomial pneumonia after introduction of preventive measures of hospital infection

In the early 1980's methicillin-resistant staphylococcus aureus (MRSA) was reported as a major pathogenic organism of geriatric hospital infection in Japan. At the same time in the A geriatric hospital MRSA infection was prevalent. To decrease nosocomial infections some active preventive measures against hospital infection were taken since Oct. 1991. About a year before introduction of prevention of hospital infection in the geriatric ward (190 beds) of A hospital 193 episodes of nosocomial bacteremia were observed. However a year after introduction of preventive measures episodes of nosocomial bacteremia were decreased to less than a half (45.6%) in comparison to the number before introduction of prevention. As a causative organism gram-positive bacteria including MRSA were markedly decreased. Major portals of entry of bacteremia (74.9%) were urinary-tract system, intravenous hyperalimentation (IVH) catheter, and pressure sores. MRSA-positive pressure sores were decreased to 20.4% of those before prevention. On the other hand 87 episodes of nosocomial pneumonia were observed before prevention. However a year after introduction of preventive measures episodes of nosocomial pneumonia were decreased to less than a half (44.8%) in comparison to the number before introduction of prevention. After prevention MRSA and mixed infection of P. aeruginosa and MRSA were markedly decreased. The decrease of bacteremia and nosocomial pneumonia were caused by cleaning hands, the preventive measures for decrease and improvement of pressure sores, cleaning the upper respiratory tract for prevention of lower respiratory-tract infection cleaning floors and education of the staff, etc.

Caractéristiques épidémiologiques, cliniques et évolutives de l'endocardite infectieuse du sujet âgé. A propos de 49 cas sur une année d'observation en région parisienne

Epidemiology, clinical manifestations and outcomes of infective endocarditis in the elderly were analysed in a study derived from a prospective nationwide survey. This study showed that (1) the clinical presentation is often misleading (2) the digestive tract represents a major portal of entry in the elderly (3) the mortality rate (37.5 %) remains worrying in this population.

Aspects of Immunology of the Gut and Rotavirus Infection

The major portal of entry for most pathogenic microorganisms is the mucosal surface. It seems reasonable therefore that the host in its turn should possess substantial immune defences at the mucosae to provide protection against these insults. Enteric infections usually result in at least some degree of specific protection against a subsequent infection with the same organism. However artificial induction of mucosal immunity has proved difficult. Clearly, as yet, we do not have a full understanding of the inductive events involved in the generation of mucosal immune responses or the immune mechanisms operating at mucosal surfaces. In this paper I will attempt to briefly review the main aspects of mucosal immunity concentrating on the gut as the model mucosal surface.

A Prospective Study of the Catheter Hub as the Portal of Entry for Microorganisms Causing Catheter-Related Sepsis in Neonates

The hypothesis that catheter-related sepsis (CRS) may be preceded by contamination of the catheter hub was tested in neonates with central venous catheters. Cultures of the catheter hub were obtained three times per week. One hundred thirteen catheters were placed in 88 patients. Of 35 episodes of sepsis, 28 were catheter-related, for a catheter sepsis rate of 1.03/100 catheter-days. CRS occurred in 26 (23%) of 113 catheters. In 10 of 28 episodes, the infecting microorganism was cultured from the hub before its culture from blood obtained at the time of clinical sepsis. In an additional 5 cases, a culture of the catheter hub at the time of clinical sepsis yielded the same isolate as the blood culture. Thus, 54% of episodes of CRS were preceded by or coincided with contamination of the hub. The catheter hub may be a major portal of entry for microorganisms causing sepsis in a neonatal intensive care unit.

Group A Streptococcal Bacteremia in a Community Teaching Hospital-- 1980-1989

This report reviews 45 episodes of group A streptococcal bacteremia during 1980-1989 in a large hospital; 24 episodes occurred in the first 5 years of study (1980-1984) and 21 in the last 5 years (1985-1989). Four episodes were nosocomial. The remaining 41 episodes were community acquired; of these episodes, 12 occurred in patients who were transferred from nursing homes. There was a definite seasonal predominance (84%) during November-June. All but three patients had chronic underlying conditions. The major portals of entry were the skin and lungs, and the main types of infection were primary septicemia, cellulitis and soft-tissue infection, pneumonia, and infective endocarditis. The overall mortality rate was 24%; 20% of the deaths were due to infection. Factors that adversely influenced mortality were septic shock (P less than .02), less than 10,000/mm3 leukocytes (P less than .05); less than 80% segmented polymorphonuclear leukocytes and band forms (P less than .02), and hyperbilirubinemia (P less than .01). Neither prevalence nor severity of group A streptococcal bacteremia increased during the last 5 years of study.

The Role of Metabolism in Chemical-Induced Pulmonary Toxicity

The lung is a target organ for the toxic effects of several chemical agents, including natural products, industrial chemicals, pesticides, environmental agents, and occasionally, drugs. Factors that establish the lung as a target organ include selective tissue exposure, high tissue oxygenation, and the presence of bioactivating systems that can generate toxic products from initially innocuous substances. Selective pulmonary exposure most often results from the fact that the lung serves as the major portal of entry for most airborne substances, but in some cases, selective exposure is the consequence of accumulation of agents, such as certain basic amines, from the circulation. Lung tumor development following long-term exposure to cigarette smoke or diesel engine exhaust is an example of pulmonary toxicity resulting from selective external exposure. Selective internal exposure, on the other hand, is exemplified by the pulmonary uptake of the herbicide paraquat from the circulation which is in part responsible for its lung-toxic effects. Although the lung contains drug metabolizing enzymes similar to those found in the liver, the enzymatic systems in the lung are sometimes highly concentrated in specific cell types. In the rabbit, for example, the lung-selective toxicity of the natural product ipomeanol is the consequence of relatively large amounts of cytochromes P450 2B1 and 4B1 in nonciliated bronchiolar epithelial cells (Clara cells) of the terminal airways. These P450 enzymes are highly proficient in vitro at converting ipomeanol to reactive products. Lung tissue contains other enzymic systems which are capable of catalyzing phase I biostransformation pathways (e.g., flavin-containing amine monooxygenase, amine oxidase, and prostaglandin synthase). Examples, however, where pulmonary metabolism by these pathways results in lung toxicity are less numerous than with P450 mediated reactions. Pulmonary prostaglandin H-synthase mediated cooxygenation has been shown to activate procarcinogens such as benzo(a)pyrene 7,8-dihydrodiol, aflatoxin B1, and monosubstituted hydrazines. The activities of pulmonary phase II (conjugation) pathways may also contribute to lung toxicity. Low glutathione transferase activity (relative to P450 mediated aryl hydrocarbon hydroxylase activity) in lung tissue has been suggested to correlate with elevated risk of lung cancer in smokers. Other examples of lung-specific toxic agents and possible causative roles of biotransformation are also discussed.

Cutaneous signals of immune system disease

The skin reflects many systemic processes. This organ, the largest of the body, has many modes of expression that are readily apparent to both the patient and the physician. Although in many instances the skin is a target of the disease process, in the case of the immune system, recent studies suggest that the skin should be considered an active component of the immune system with the capacity for cell maturation. The skin and the immune system are genetically related. This is revealed by the fact that hairless (nude) animal strains all lack thymuses, and by chromosome mapping studies, which place loci relating to hair growth and genes which control the immune response on the same chromosome. As a major portal of entry for all infectious agents, integrity of the skin and its defense mechanisms is required to prevent ingress of bacteria, viruses, and fungi. Failure of the immune system to eliminate infectious agents can be strikingly demonstrated by persistent eczematous, blistering, or granulomatous lesions. Diagnosis of major immunodeficiency states can be made from the appearance of such signs as total alopecia in infants, the telangiectasia of ataxia-telangiectasia, and Kaposi's sarcoma in adults. The immune system has an extraordinary capacity for differentiating between the millions of antigenic stimuli to which it can respond. It also has a variety of methods by which to eliminate infectious agents from the body. All of this capability requires many specialized, clonally-derived cells that work with other cells and molecules in a highly orchestrated manner. This allows for a certain amount of redundancy to provide a number of backup systems. On the other hand, the complexity of the system allows for many sources of error, so definition of the cause of immunodeficiency is difficult. Modern technology has permitted much greater precision in the delineation of immunodeficiency diseases. A few years ago, immunodeficiency was a rare genetic disorder. Two major events have changed this situation. One is the epidemic of acquired immunodeficiency syndrome (AIDS), which in 10 years' time has become a major if not the major health problem of the country. A second cause of immunodeficiency is the widespread use of immunosuppressive drugs for control of transplantation or cancer. Transplantation, particularly of the bone marrow, which is now performed at a rate of thousands per year, also produces immunodeficiency because of the unusual physiology of graft-versus-host disease (GVHD). The cutaneous manifestations of GVHD are among the most fascinating phenomena of immunopathology. The continued overlap of the disciplines of dermatology and immunology has been a challenge to both laboratory and clinical scientists.

Klebsiella bacteremia: A review of 196 episodes during a decade (1980–1989)

This report reviews 196 episodes of klebsiella bacteremia in 194 patients during a 10-year period (1980-1989) in a community teaching hospital in the USA. The median age of patients was 70 years with a mode of 84 years. The prevalence was 0.76 episodes/1000 admissions. Nosocomial acquisition of bacteremia occurred in 43% of episodes and 16% of patients were from nursing homes. Klebsiella pneumoniae accounted for 86% and K. oxytoca for 13% of episodes. Most isolates were resistant to ampicillin and carbenicillin but susceptible to other antimicrobial agents tested. 55 episodes (28%) were polymicrobial; Escherichia coli and enterococci were the most common co-isolates. The major portals of entry were the respiratory tract and urinary tract. The majority of patients had major underlying conditions. The overall mortality was 37%. Factors that adversely influenced the mortality rate were nosocomial bacteremia, polymicrobial bacteremia, respiratory tract as the portal of entry, rapidly fatal and ultimately fatal underlying conditions, septic shock, severe leukopenia, increases in total serum bilirubin level or serum creatinine level and inappropriate antimicrobial therapy.

Pathogenesis of postoperative candidosis: no detectable fungemia during reoperations after abdominal surgery

Pathogenesis of systemic candidosis in surgical patients is unsettled. Results from animal models suggest that invasion from colonized intestine is the major portal of entry into circulation. To study the mechanisms of systemic candidosis in surgical patients after intestinal surgery, multiple blood cultures were taken during reoperations with manipulation of the intestinum to detect possible perioperative fungemia. The lysis centrifugation method (Isolator) was used for blood cultures. Of the 30 subjects in the material, 12 were demonstrated to be colonized with yeast before the reoperation. Three patients had positive blood cultures during reoperation, but no yeasts were found in the 146 perioperative blood cultures. Three patients had severe nonsuperficial yeast infection after reoperation, but none had disseminated candidosis. This finding in high risk patients supports the view that immediate perioperative fungemia and persorption from colonized intestinum is rare. However, persorption may occur later via healing wounds of the colonized intestinum. Both persorption and the exogenous route (e.g. vascular catheters) are possible in the pathogenesis of postoperative candidosis.

The Role of Metabolism in Chemical-Induced Pulmonary Toxicity*1

The lung is a target organ for the toxic effects of several chemical agents, including natural products, industrial chemicals, pesticides, environmental agents, and occasionally, drugs. Factors that establish the lung as a target organ include selective tissue exposure, high tissue oxygenation, and the presence of bioactivating systems that can generate toxic products from initially innocuous substances. Selective pulmonary exposure most often results from the fact that the lung serves as the major portal of entry for most airborne substances, but in some cases, selective exposure is the consequence of accumulation of agents, such as certain basic amines, from the circulation. Lung tumor development following long-term exposure to cigarette smoke or diesel engine exhaust is an example of pulmonary toxicity resulting from selective external exposure. Selective internal exposure, on the other hand, is exemplified by the pulmonary uptake of the herbicide paraquat from the circulation which is in part responsible for its lung-toxic effects. Although the lung contains drug metabolizing enzymes similar to those found in the liver, the enzymatic systems in the lung are sometimes highly concentrated in specific cell types. In the rabbit, for example, the lung-selective toxicity of the natural product ipomeanol is the consequence of relatively large amounts of cytochromes P450 2B1 and 4B1 in nonciliated bronchiolar epithelial cells (Clara cells) of the terminal airways. These P450 enzymes are highly proficient in vitro at converting ipomeanol to reactive products. Lung tissue contains other enzymic systems which are capable of catalyzing phase I biostransformation pathways (e.g., flavin-containing amine monooxygenase, amine oxidase, and prostaglandin synthase). Examples, however, where pulmonary metabolism by these pathways results in lung toxicity are less numerous than with P450 mediated reactions. Pulmonary prostaglandin H-synthase mediated cooxygenation has been shown to activate procarcinogens such as benzo(a)pyrene 7,8-dihydrodiol, aflatoxin B1, and monosubstituted hydrazines. The activities of pulmonary phase II (conjugation) pathways may also contribute to lung toxicity. Low glutathione transferase activity (relative to P450 mediated aryl hydrocarbon hydroxylase activity) in lung tissue has been suggested to correlate with elevated risk of lung cancer in smokers. Other examples of lung-specific toxic agents and possible causative roles of biotransformation are also discussed.

Oral aspergillosis in a patient with acquired immunodeficiency syndrome

Aspergillus is the most common fungus in the environment. It is found in soil and decaying vegetation. Its spores become airborne, are swallowed or inhaled, and enter the lower respiratory tract, which is the major portal of entry into the body.’ Many forms of aspergillosis exist. One form, a local aspergilloma, is a “fungus ball” within pulmonary cavities. It is composed of tangled mycelia, fibrin, and amorphous debris. Aspergilloma can also occur in the paranasal sinuses and orbit, often being confused with a neoplasm because of its chronic nature and invasion of contiguous structures.* Another form of the disease, disseminated aspergillosis, has been reported with increasing frequency in recent years among cancer patients and others with compromised immune systems. It is the second most common fungal infection in patients with malignant disorders. Pulmonary involvement is present in almost all cases of invasive aspergillosis seen in this patient population.3 Aspergillosis spores also have the proclivity to germinate into proliferative hyphae in any mucous medium and may demonstrate a more localized mucosal form. This capacity enables the organism to colonize oronasal portals of entry and to produce infections that invade contiguous structures in the maxillofacial region.4 Invasive fungal disease is a process whereby common fungal species may become aggressively opportunistic pathogens in certain hosts. The most familiar and best studied is the rhizopus Mucor species, which is classically seen in diabetic individuals. In mucormycosis, the organism gains entry into

Enterobacter bacteremia: a review of 58 episodes.

This report reviews 58 episodes of enterobacter bacteremia in 55 patients during a 66-month period at a 750-bed community teaching hospital in USA. The median age of patients was 65 years and 38% of the patients were older than 70 years. All patients had underlying conditions: rapidly fatal (7%), ultimately fatal (33%) and non-fatal (60%). Nosocomial acquisition of bacteremia occurred in 72% of episodes. 20 episodes (34.5%) were polymicrobial bacteremia. The major portal of entry was the lungs (34%). The overall mortality was 69%. Factors that adversely influenced the mortality rate were nosocomial acquisition (p less than 0.02), rapidly fatal and ultimately fatal underlying conditions (p less than 0.02), and lungs as the portal of entry (p less than 0.05).

Serratia Bacteremia: A Review of 44 Episodes

This report reviews 44 episodes of serratia bacteremia over a 9-year period (1980-1988) in a community-teaching hospital in the USA. The median age of patients was 64 years and 34% of the patients were older than 70 years. Nosocomial acquisition of bacteremia occurred in 70% of episodes, and 11% of patients were admitted from nursing homes. Nine episodes (20%) were polymicrobial bacteremia. The major portals of entry were the lower respiratory tract (11 episodes) and the urinary tract (6 episodes). The overall mortality was 52%. Factors that adversely influenced the mortality rate were rapidly fatal and ultimately fatal underlying conditions (p less than 0.001), platelet counts less than or equal to 100 x 10(0)/l at the onset of bacteremia (p less than 0.01), and total serum bilirubin greater than 18 mumol/l at the onset of bacteremia (p less than 0.01). All serratia strains tested were susceptible to gentamicin, kanamycin, amikacin and ceftizoxime.

Proposed mechanisms for the translocation of intestinal bacteria.

Members of the endogenous flora have become recognized as major pathogens in nosocomial infections, and the intestinal tract has become recognized as a major portal of entry for these pathogens. The English-language literature on this topic has been summarized and a working hypothesis devised describing a mechanism whereby intestinal bacteria can escape and cause systemic disease. It is postulated that the motile phagocyte ingests intestinal bacteria, transports them to extraintestinal sites, fails to accomplish intracellular killing, and then liberates the bacteria in the extraintestinal site. This hypothesis is consistent with many observations found in the literature: (1) The intestinal bacteria that most readily translocate out of the intestinal tract are classified as facultative intracellular pathogens. (2) Intestinal particles with no intrinsic motility (e.g., yeast, ferritin, starch) can translocate out of the intestinal lumen within hours after their ingestion. (3) The rate of translocation of intestinal bacteria can be altered with agents that modulate immune (including phagocytic) function. In the context of the mechanisms involved in intestinal immune responses, bacterial translocation appears to be a part of the normal antigen-sampling process of gut-associated lymphoid tissue. Systemic disease caused by translocating intestinal bacteria could be due to a maladaptation of the antigen-sampling process that has been designed to regulate the immune response to intestinal antigens.