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Previous studies in school children have demonstrated the slow development with age of resistance to reinfection after chemotherapy of Schistosoma mansoni infections, and have indicated that inappropriate ("blocking") antibody responses prevent the expression of immunity in young children. The present study was designed to investigate further the nature of the protective responses, by serological studies on a group of 151 S. mansoni-infected individuals resident in an endemic area in Machakos District, Kenya. Antibody levels against various antigens in blood samples before treatment were related to intensity of previous infections; antibodies in blood samples taken 6 months after treatment were related to cumulative reinfection rates over the following 30 months. IgE against an adult-worm antigen preparation correlated positively with age and negatively with reinfection. In contrast, IgE antibodies against other life-cycle stages showed either no relationship or the reverse correlation. Furthermore, antibodies of other isotypes against adult-worm antigens showed no correlations with reinfection. The correlation with IgE could be demonstrated for different preparations of adult worms, including a periodate-treated preparation presumptively depleted of carbohydrate epitopes. For both the intact and the periodate-treated preparations, multiple regression analysis of the results for children less than or equal to 16 years old demonstrated an IgE effect after allowing for age, although this effect was not observed in a previously studied group of school children. Western blot analysis of the adult-worm preparation revealed a limited set of antigens recognized by IgE, among which an antigen of 22 kDa was prominent. The qualitative presence of IgE against this antigen could also be shown to be related to a lack of subsequent reinfection.
Previous studies in school children have demonstrated the slow development with age of resistance to reinfection after chemotherapy of Schistosoma mansoni infections, and have indicated that inappropriate ("blocking") antibody responses prevent the expression of immunity in young children. The present study was designed to investigate further the nature of the protective responses, by serological studies on a group of 151 S. mansoni-infected individuals resident in an endemic area in Machakos District, Kenya. Antibody levels against various antigens in blood samples before treatment were related to intensity of previous infections; antibodies in blood samples taken 6 months after treatment were related to cumulative reinfection rates over the following 30 months. IgE against an adult-worm antigen preparation correlated positively with age and negatively with reinfection. In contrast, IgE antibodies against other life-cycle stages showed either no relationship or the reverse correlation. Furthermore, antibodies of other isotypes against adult-worm antigens showed no correlations with reinfection. The correlation with IgE could be demonstrated for different preparations of adult worms, including a periodate-treated preparation presumptively depleted of carbohydrate epitopes. For both the intact and the periodate-treated preparations, multiple regression analysis of the results for children less than or equal to 16 years old demonstrated an IgE effect after allowing for age, although this effect was not observed in a previously studied group of school children. Western blot analysis of the adult-worm preparation revealed a limited set of antigens recognized by IgE, among which an antigen of 22 kDa was prominent. The qualitative presence of IgE against this antigen could also be shown to be related to a lack of subsequent reinfection.
SummaryIt has been suggested that neutrophils may be involved in the late-phase reaction of immunoglobulin E (IgE)-dependent hypersensitivity states. However, the identity of neutrophil-associated molecules inducing the release of mediators remains undear. In this report, we demonstrate that human neutrophils from normal donors or from patients with inflammatory disorders could bind myeloma IgE proteins, especially after desialylation. Northern blot, immunoprecipitation, and flow cytometry analyses revealed that neutrophils did not express FceRII/CD23, but rather Mac-2/e binding protein (BP), belonging to the S-type lectin family. Similarly to IgA used as positive control, myeloma IgE proteins, as well as polyclonal IgE antibodies with or without antibody specificity, were both capable of inducing a neutrophil respiratory burst. Anti-Mac-2 but not anti-CD23 mAb strongly decreased the IgE-dependent activation of neutrophils, induced either by the specific antigen or by anti-IgE antibodies. These findings open new perspectives on the functional role of neutrophils in IgE-associated diseases including allergic states or parasitic infections.I nflammatory reactions generally involve a vast array of mediators and a variety of effector cells such as mast cells, macrophages, eosinophils, platelets, and neutropb.ils. Among them, neutrophils have been rather neglected in studies concerning allergic diseases, although an increase in neutrophil numbers and activity was found to be correlated to airway hyperresponsiveness in asthmatic patients (1). These findings have suggested that neutrophils might play a role in allergic diseases characterized by a marked elevation of serum IgE, such as asthma, especially during the late-phase reaction. However, neutrophils represent the only blood cell population that does not seem to express conventional Fc receptors for IgE, neither FceRI, like basophils or mast cells (2), nor FceRII, like macrophages, eosinophils, or platelets (3). Besides these IgE Fc receptors, a new family of IgE-binding molecules has been recently described. They belong to S-type lectins with the ability to bind IgE through carbohydrate recognition domain (4). Members of the family include Mac-2/eBP, which are endogenous soluble lectins and can be expressed by various cell types (5, 6). One feature of eBP molecules is their restricted recognition by specific glycoforms of IgE. It is interesting that the majority of myeloma IgE proteins and polydonal IgE from some patients are able to bind to eBP only after desialylation (5, 7). In this respect, it has to be mentioned that the few IgE binding assays previously reported on human neutrophils (8, 9) have been performed with myeloma IgE proteins, and therefore did not allow us to investigate the existence of functional interactions between neutrophils and IgE antibodies from patients. The wide cell distribution of Mac-2/eBP molecules and their recent demonstration in eosinophils from hypereosinophilic patients (10) led us to investigate their possible existence in hum...
This paper proposes that the mammalian immune response known as "allergy" evolved as a last line of defense against the extensive array of toxic substances that exist in the environment in the form of secondary plant compounds and venoms. Whereas nonimmunological defenses typically can target only classes of toxins, the immune system is uniquely capable of the fine-tuning required to target selectively the specific molecular configurations of individual toxins. Toxic substances are commonly allergenic. The pharmacological chemicals released by the body's mast cells during an IgE antibody-mediated allergic response typically cause vomiting diarrhea, coughing, tearing, sneezing, or scratching, which help to expel from the body the toxic substance that triggered the response; individuals frequently develop aversions to substances that have triggered such responses. A strong allergic response often includes a decrease in blood pressure, which slows the rate at which toxins circulate to target organs. The immune system identifies as toxic the following kinds of substances: (1) those low-molecular-weight substances that bind covalently to serum proteins (e.g., many plant toxins); (2) nontoxic proteins that act as carriers of toxins with low molecular weights (e.g., plant proteins associated with plant toxins); (3) specific substances of high molecular weight that harmed individuals in ancestral mammalian populations for a span of time that was significant from the standpoint of natural selection (e.g., the toxic proteins of bee venom. Substances that bind covalently to serum proteins generally are acutely toxic, and because many of these substances also bind covalently to the DNA of target cells, they are potentially mutagenic and carcinogenic as well. Thus, by protecting against acute toxicity, allergy may also defend against mutagens and carcinogens. The toxic hypothesis explains the main phenomena of allergy; why IgE-mediated allergies usually occur within minutes of exposure to an allergen and why they are often so severe; why the manifestations of allergy include vomiting, diarrhea, coughing, sneezing, scratching, tearing, and a drop in blood pressure; why covalent binding of low-molecular-weight substances to serum proteins frequently causes allergy; why allergies occur to many foods, pollens, venoms, metals, and drugs; why allergic cross-reactivity occurs to foods and pollen from unrelated botanical families; why allergy appears to be so capricious and variable; and why allergy is more prevalent in industrial societies than it is in foraging societies. This hypothesis also has implications for the diagnosis, prevention, and treatment of allergy.
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