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1.
Ann Oncol ; 23(5): 1314-1319, 2012 May.
Artículo en Inglés | MEDLINE | ID: mdl-21930686

RESUMEN

BACKGROUND: IMM-101 is a heat-killed innate and adaptive immune-activating mycobacterial product; a phase I study aimed to determine its safety and tolerability in individuals with melanoma. PATIENTS AND METHODS: An intra-patient placebo-controlled study evaluated the safety and tolerability of three doses, namely, 0.1 (1 mg/ml), 0.5 (5 mg/ml) and 1.0 mg (10 mg/ml) of IMM-101 in stage III or IV melanoma. Each dose was administered in ascending order to one of the three cohorts. RESULTS: Based on observations from patients administered the 0.1-mg dose, it was considered appropriate to proceed with dosing the patients in the 0.5-mg dose cohort and then the 1.0-mg cohort (n = 6 per cohort). Treatment-emergent adverse events that would be considered typical of a post-vaccination state (including joint pains/aches, headaches and influenza-like symptoms) occurred at all dose levels, along with injection site reactions. These were mainly mild in intensity, resolved in a matter of days and responded well to supportive care. During post-study follow-up, two clinical responses (15%) were observed in patients with stage IV disease. CONCLUSION: IMM-101 is safe and well tolerated and there is a rationale for studying IMM-101 at a nominal 1.0-mg dose to complement conventional cytotoxic therapy for patients with advanced cancer.


Asunto(s)
Antineoplásicos/administración & dosificación , Antineoplásicos/efectos adversos , Vacunas contra el Cáncer/administración & dosificación , Vacunas contra el Cáncer/efectos adversos , Melanoma/terapia , Neoplasias Cutáneas/terapia , Adulto , Anciano , Vacunas Bacterianas/administración & dosificación , Vacunas Bacterianas/efectos adversos , Relación Dosis-Respuesta a Droga , Femenino , Estudios de Seguimiento , Humanos , Inmunoterapia/efectos adversos , Inyecciones Intradérmicas , Masculino , Melanoma/inmunología , Persona de Mediana Edad , Modelos Biológicos , Mycobacterium/inmunología , Placebos , Neoplasias Cutáneas/inmunología
2.
Neuroscience ; 146(2): 756-72, 2007 May 11.
Artículo en Inglés | MEDLINE | ID: mdl-17367941

RESUMEN

Peripheral immune activation can have profound physiological and behavioral effects including induction of fever and sickness behavior. One mechanism through which immune activation or immunomodulation may affect physiology and behavior is via actions on brainstem neuromodulatory systems, such as serotonergic systems. We have found that peripheral immune activation with antigens derived from the nonpathogenic, saprophytic bacterium, Mycobacterium vaccae, activated a specific subset of serotonergic neurons in the interfascicular part of the dorsal raphe nucleus (DRI) of mice, as measured by quantification of c-Fos expression following intratracheal (12 h) or s.c. (6 h) administration of heat-killed, ultrasonically disrupted M. vaccae, or heat-killed, intact M. vaccae, respectively. These effects were apparent after immune activation by M. vaccae or its components but not by ovalbumin, which induces a qualitatively different immune response. The effects of immune activation were associated with increases in serotonin metabolism within the ventromedial prefrontal cortex, consistent with an effect of immune activation on mesolimbocortical serotonergic systems. The effects of M. vaccae administration on serotonergic systems were temporally associated with reductions in immobility in the forced swim test, consistent with the hypothesis that the stimulation of mesolimbocortical serotonergic systems by peripheral immune activation alters stress-related emotional behavior. These findings suggest that the immune-responsive subpopulation of serotonergic neurons in the DRI is likely to play an important role in the neural mechanisms underlying regulation of the physiological and pathophysiological responses to both acute and chronic immune activation, including regulation of mood during health and disease states. Together with previous studies, these findings also raise the possibility that immune stimulation activates a functionally and anatomically distinct subset of serotonergic neurons, different from the subset of serotonergic neurons activated by anxiogenic stimuli or uncontrollable stressors. Consequently, selective activation of specific subsets of serotonergic neurons may have distinct behavioral outcomes.


Asunto(s)
Corteza Cerebral/inmunología , Emociones/fisiología , Sistema Límbico/inmunología , Neuronas/metabolismo , Núcleos del Rafe/citología , Serotonina/metabolismo , Análisis de Varianza , Animales , Vacunas Bacterianas/administración & dosificación , Vacunas Bacterianas/farmacología , Conducta Animal , Química Encefálica/efectos de los fármacos , Secuestro Broncopulmonar/inducido químicamente , Secuestro Broncopulmonar/inmunología , Secuestro Broncopulmonar/metabolismo , Corteza Cerebral/metabolismo , Citocinas/metabolismo , Modelos Animales de Enfermedad , Vías de Administración de Medicamentos , Emociones/efectos de los fármacos , Sistema Límbico/metabolismo , Masculino , Ratones , Ratones Endogámicos BALB C , Vías Nerviosas/efectos de los fármacos , Vías Nerviosas/inmunología , Vías Nerviosas/metabolismo , Núcleos del Rafe/efectos de los fármacos , Núcleos del Rafe/metabolismo , Factores de Tiempo
3.
Gut ; 54(3): 317-20, 2005 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-15710972

RESUMEN

Two distinct, but rapidly converging, areas of research (the hygiene hypothesis and the study of probiotic/prebiotic effects) have emphasised the need to understand, and ultimately to manipulate, our physiological interactions with commensal flora, and with other transient but harmless organisms from the environment that affect immunoregulatory circuits. The story began with allergic disorders but now inflammatory bowel disease is increasingly involved.


Asunto(s)
Enfermedades del Sistema Inmune/microbiología , Enfermedades Inflamatorias del Intestino/inmunología , Intestinos/microbiología , Humanos , Higiene , Intestinos/inmunología , Probióticos , Subgrupos de Linfocitos T/inmunología
4.
Bull World Health Organ ; 79(10): 916-25, 2001.
Artículo en Inglés | MEDLINE | ID: mdl-11693973

RESUMEN

BACKGROUND: Lone Star ticks (Amblyomma americanum) have been suggested as a vector of the agent of Lyme disease (Borrelia burgdorferi sensu lato) in the USA, based on associations with an infection manifesting mainly as erythema migrans. In laboratory experiments, however, they failed to transmit B. burgdorferi sensu stricto. METHODS: In this study, carried out from 1994 to 1996, we determined the seroprevalences of B. burgdorferi (1.2%), Ehrlichia chaffeensis (7%), E. phagocytophila (0%), Rickettsia rickettsii (0%), R. typhi (0%), Coxiella burneti (0%), Francisella tularensis (0%), and Babesia microti (0%) by standard serological methods for 325 residents (97% of the total population) of Gibson Island, coastal Maryland, USA, where 15% of the residents reported having had Lyme disease within a recent 5-year span. FINDINGS: Of the 167 seronegative individuals who were followed up prospectively for 235 person-years of observation, only 2 (0.85%) seroconverted for B. burgdorferi. Of 1556 ticks submitted from residents, 95% were identified as Lone Star ticks; only 3% were deer ticks (Ixodes dammini), the main American vector of Lyme disease. B. burgdorferi s.s. infected 20% of host-seeking immature deer ticks, and borreliae ("B. lonestari") were detected in 1-2% of Lone Star ticks. Erythema migrans was noted in 65% of self-reports of Lyme disease, but many such reports indicated that the rash was present while the tick was still attached, suggesting a reaction to the bite itself rather than true Lyme disease. Sera from individuals reporting Lyme disease generally failed to react to B. burgdorferi or any other pathogen antigens. CONCLUSION: The residents of Gibson Island had an exaggerated perception of the risk of Lyme disease because they were intensely infested with an aggressively human-biting and irritating nonvector tick. In addition, a Lyme disease mimic of undescribed etiology (named Masters' disease) seems to be associated with Lone Star ticks, and may confound Lyme disease surveillance. The epidemiological and entomological approach used in this study might fruitfully be applied wherever newly emergent tickborne zoonoses have been discovered.


Asunto(s)
Actitud Frente a la Salud , Enfermedad de Lyme/epidemiología , Adulto , Animales , Vectores Arácnidos , Borrelia burgdorferi/aislamiento & purificación , Estudios Transversales , Femenino , Humanos , Mordeduras y Picaduras de Insectos , Ixodidae/microbiología , Enfermedad de Lyme/diagnóstico , Enfermedad de Lyme/psicología , Enfermedad de Lyme/transmisión , Masculino , Maryland/epidemiología , Cooperación del Paciente , Factores de Riesgo , Estudios Seroepidemiológicos , Encuestas y Cuestionarios
5.
J Leukoc Biol ; 70(5): 737-44, 2001 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-11698493

RESUMEN

T cell responses of interleukin (IL)-4(-/-) and wild-type (WT) mice infected with the helper T cell 2 (Th2) response-inducing pathogen Schistosoma mansoni were compared. As expected, given the important role of IL-4 in Th2 response induction, the absence of IL-4 resulted in diminished Th2 responses, apparent as reduced production of IL-4, -5, and -10 by CD4(+) cells isolated from the spleens of infected IL-4(-/-) mice. Surprisingly, these cells produced significantly less interferon (IFN)-gamma and proliferated less than did those from infected WT mice after T cell receptor ligation. CD8(+) cells isolated from infected IL-4(-/-) mice also produced less IFN-gamma than WT CD8 cells, although there was no difference in the proliferative responses of these cell populations. After infection, spleens of infected IL-4(-/-) mice did not enlarge to the same extent as those of WT mice, and attrition of the CD8(+) cell population within this lymphoid organ was noted. Taken together, the data indicate that in addition to inhibiting Th2 response development, the lack of IL-4 during schistosomiasis significantly affects additional aspects of T cell responses.


Asunto(s)
Interleucina-4/fisiología , Linfocinas/metabolismo , Esquistosomiasis mansoni/inmunología , Subgrupos de Linfocitos T/inmunología , Animales , Apoptosis , Linfocitos T CD8-positivos/efectos de los fármacos , Linfocitos T CD8-positivos/inmunología , Linfocitos T CD8-positivos/metabolismo , Progresión de la Enfermedad , Femenino , Hiperplasia , Síndromes de Inmunodeficiencia/etiología , Síndromes de Inmunodeficiencia/inmunología , Interferón gamma/metabolismo , Interleucina-10/metabolismo , Interleucina-13/metabolismo , Interleucina-2/farmacología , Interleucina-4/deficiencia , Interleucina-4/genética , Interleucina-5/metabolismo , Activación de Linfocitos , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Muromonab-CD3/farmacología , Esquistosomiasis mansoni/patología , Bazo/patología , Esplenomegalia/etiología , Subgrupos de Linfocitos T/metabolismo , Células Th2/inmunología , Células Th2/metabolismo
6.
Int Immunopharmacol ; 1(8): 1457-67, 2001 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-11515811

RESUMEN

Nitric oxide (NO) is implicated as an integral component of the host armament against invading parasites. Strongest evidence has come from laboratory models of protozoan infections. During malaria, toxoplasmosis and leishmaniasis, to name just a few, the preferential production of pro-inflammatory cytokines predisposes to the increased synthesis of NO, which mediates host protection through either direct parasite killing or by limiting parasite growth. More recently, evidence has been put forward for a beneficial role of NO during helminthic infections. In the case of Schistosomiasis mansoni, for example, NO plays a role in regulation of egg-induced inflammation, preventing hepatocyte death and widespread tissue damage. In spite of these findings, rather than being the ultimate panacea, NO production requires tight control to limit cytotoxic damage to the host's own cells. Unregulated production may lead to a variety of damaging effects including alterations to normal neurological functions during cerebral malaria and intestinal pathology during trichinosis. In this review, I will summarize the role of NO during a number of parasitic infections, drawing on specific examples of disease caused by protozoan and metazoan parasites.


Asunto(s)
Óxido Nítrico/fisiología , Enfermedades Parasitarias/metabolismo , Animales , Humanos , Enfermedades Parasitarias/inmunología , Enfermedades Parasitarias/parasitología
7.
Infect Immun ; 69(1): 589-92, 2001 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-11119559

RESUMEN

An interleukin-4 (IL-4)-dependent Th2 response allows wild-type mice to survive infection with the parasite Schistosoma mansoni. In the absence of IL-4, infected mice mount a Th1-like proinflammatory response, develop severe disease, and succumb. Neither the Th1 response nor morbidity is IL-12 dependent in this system.


Asunto(s)
Interleucina-12/fisiología , Interleucina-4/fisiología , Esquistosomiasis mansoni/inmunología , Animales , Interferón gamma/fisiología , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Óxido Nítrico/fisiología , Factor de Necrosis Tumoral alfa/fisiología
8.
Parasitology ; 120 ( Pt 6): 565-71, 2000 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-10874719

RESUMEN

This study investigated the nature of the immune response of C57BL/6 mice infected with the trematode Echinostoma caproni. To determine the preferential development of either a Th1 or Th2 cytokine pattern during early stages of infection, cytokine production by spleen and mesenteric lymph node (MLN) cells during the first 3 weeks of infection was followed. Whereas spleen cells failed to respond to antigen stimulation, MLN cells produced IFN-gamma and to a lesser extent IL-4. IL-5 levels were elevated throughout the period studied. The humoral response was consistent with a Th1 cytokine pattern as antigen-specific IgG2a antibodies were preferentially developed. We investigated whether IFN-gamma is critical for establishment of E. caproni infection. Worm burden in infected mice treated with a single injection of anti-IFN-gamma mAb was significantly reduced compared to that of animals treated with a control antibody.


Asunto(s)
Echinostoma/inmunología , Equinostomiasis/inmunología , Interferón gamma/biosíntesis , Interleucina-4/biosíntesis , Interleucina-5/biosíntesis , Animales , Anticuerpos Antihelmínticos/sangre , Anticuerpos Monoclonales/uso terapéutico , Antígenos Helmínticos/análisis , Antígenos Helmínticos/inmunología , Peso Corporal , Equinostomiasis/parasitología , Ensayo de Inmunoadsorción Enzimática , Femenino , Citometría de Flujo , Interferón gamma/análisis , Interferón gamma/inmunología , Interleucina-4/análisis , Interleucina-5/análisis , Intestinos/parasitología , Ganglios Linfáticos/parasitología , Ratones , Ratones Endogámicos C57BL , Linfocitos T/inmunología
9.
J Immunol ; 163(9): 4976-84, 1999 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-10528202

RESUMEN

During infection with Schistosoma mansoni, NO production increases following the deposition of parasite eggs in the liver. In wild-type C57BL/6 mice, NO levels peak during the sixth week of infection and are subsequently down-regulated. Inducible NO synthase (iNOS) mRNA was found in diseased liver tissue along with TNF-alpha and IFN-gamma, which are known promoters of iNOS expression. Mice treated with aminoguanidine, a selective inhibitor of iNOS, exhibited cachexia and exacerbated liver pathology, suggesting that NO limits hepatocyte damage when the liver is first exposed to eggs. Hepatic iNOS is up-regulated in SCID mice, indicating that NO production is part of an innate response. Studies with infected highly susceptible IL-4-/- mice revealed that prolonged NO production is in itself deleterious and that a major function of the Th2 response, which is severely compromised in the absence of IL-4, is to regulate NO production. In these animals, plasma NO levels are high compared with those in infected wild-type mice and remain elevated until death. Nevertheless, the underlying importance of NO is illustrated by the finding that aminoguanidine treatment leads to more severe liver disease and reduced time to death in infected IL-4-/- mice.


Asunto(s)
Parasitosis Hepáticas/patología , Parasitosis Hepáticas/prevención & control , Hígado/patología , Óxido Nítrico/fisiología , Esquistosomiasis mansoni/patología , Esquistosomiasis mansoni/prevención & control , Células Th2/inmunología , Células Th2/metabolismo , Animales , Apoptosis/inmunología , Hepatomegalia/inmunología , Hepatomegalia/patología , Interferón gamma/biosíntesis , Hígado/inmunología , Hígado/parasitología , Parasitosis Hepáticas/inmunología , Parasitosis Hepáticas/metabolismo , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Ratones SCID , Óxido Nítrico/biosíntesis , Óxido Nítrico Sintasa/antagonistas & inhibidores , Óxido Nítrico Sintasa de Tipo II , Esquistosomiasis mansoni/inmunología , Esquistosomiasis mansoni/metabolismo , Esplenomegalia/inmunología , Esplenomegalia/patología , Células Th2/enzimología , Factor de Necrosis Tumoral alfa/biosíntesis
10.
J Parasitol ; 85(4): 734-6, 1999 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-10461958

RESUMEN

To ask whether type-2 immune responses serve an essential role in concomitant immunity, that is the prevention of superinfection with Schistosoma mansoni, we compared resistance to a challenge infection in infected wild-type (WT) mice and in infected IL-4-/- mice, which are unable to mount Th2 responses during schistosomiasis. Although WT mice are protected from superinfection, resistance is abrogated in the absence of interleukin (IL)-4. We conclude that IL-4 or IL-4-dependent responses, or both, are necessary for resistance to S. mansoni superinfection in mice.


Asunto(s)
Interleucina-4/inmunología , Esquistosomiasis mansoni/inmunología , Animales , Inmunidad Celular , Interleucina-4/genética , Ratones , Ratones Mutantes , Modelos Inmunológicos , Sobreinfección , Células Th2
11.
J Immunol ; 163(4): 2089-97, 1999 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-10438948

RESUMEN

To address the question of how the murine host responds to a prototypic type 1 cytokine inducer while concurrently undergoing a helminth-induced type 2 cytokine response, C57BL/6 strain animals with patent schistosomiasis mansoni were orally infected with the cystogenic Toxoplasma gondii strain ME49. Schistosoma mansoni infection resulted in a significantly higher mortality rate when mice were subsequently orally infected with ME49, and these animals displayed a defective IFN-gamma and NO response relative to animals infected with T. gondii alone. Plasma levels of TNF-alpha and aspartate transaminase in double-infected mice were greatly elevated relative to mice infected with either parasite alone. Consistent with the latter observation, these animals exhibited severe liver pathology, with regions of coagulative necrosis and hepatocyte vacuolization unapparent in mice carrying either infection alone. Interestingly, mean egg granuloma size was approximately 50% of that in mice with S. mansoni infection alone. The exacerbated liver pathology in coinfected mice did not appear to be a result of uncontrolled tachyzoite replication, because both parasite-specific RT-PCR analysis and immunohistochemical staining demonstrated a low number of tachyzoites in the liver. We hypothesize that mortality in these animals results from the high level of systemic TNF-alpha, which mediates a severe liver pathology culminating in death of the animal.


Asunto(s)
Parasitosis Hepáticas/mortalidad , Parasitosis Hepáticas/patología , Schistosoma mansoni/patogenicidad , Esquistosomiasis mansoni/patología , Toxoplasma/patogenicidad , Factor de Necrosis Tumoral alfa/metabolismo , Animales , Susceptibilidad a Enfermedades , Femenino , Inmunoglobulina E/sangre , Interferón gamma/biosíntesis , Interferón gamma/sangre , Parasitosis Intestinales/patología , Parasitosis Hepáticas/inmunología , Parasitosis Hepáticas/parasitología , Ratones , Ratones Endogámicos C57BL , Schistosoma mansoni/inmunología , Esquistosomiasis mansoni/sangre , Esquistosomiasis mansoni/inmunología , Esquistosomiasis mansoni/mortalidad , Toxoplasma/crecimiento & desarrollo , Toxoplasma/inmunología , Toxoplasmosis Animal/inmunología , Toxoplasmosis Animal/mortalidad , Toxoplasmosis Animal/parasitología , Toxoplasmosis Animal/patología
12.
Infect Immun ; 67(6): 3014-8, 1999 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-10338513

RESUMEN

During schistosomiasis, interleukin-5 (IL-5)-dependent eosinophil responses have been implicated in immunopathology, resistance to superinfection, synergistic interactions with chemotherapeutic agents, and the inductive phase of the egg-induced Th2 response. We examined these issues in IL-5-deficient (IL-5(-/-)) mice. IL-5(-/-) and wild-type (WT) mice were indistinguishable in terms of susceptibility to primary infections and the ability to resist secondary infections. Moreover, hepatic pathology was similar in both strains apart from a relative lack of eosinophils and, during chronic infection, a significantly larger mast cell component in the granulomas of IL-5(-/-) mice. Splenocyte cytokine production in response to soluble egg antigen (SEA) or anti-CD3 revealed no significant differences except for heightened tumor necrosis factor alpha production by cells from chronically infected IL-5(-/-) mice compared to WT animals. In contrast, ionomycin-stimulated non-B, non-T (NBNT) cells from IL-5(-/-) mice produced significantly smaller IL-4 amounts than did NBNT cells from WT animals. This difference was not apparent following plate-bound anti-immunoglobulin E or SEA stimulation. The absence of IL-5 failed to affect the induction of Th2 responses in naive mice. Peritoneal exudate cells recovered from egg-injected IL-5(-/-) or WT mice produced equivalent levels of IL-4 following restimulation with SEA or anti-CD3.


Asunto(s)
Interleucina-4/biosíntesis , Interleucina-5/inmunología , Esquistosomiasis mansoni/inmunología , Células Th2/inmunología , Animales , Linfocitos B/inmunología , Biomphalaria , Inmunidad Innata/inmunología , Interleucina-5/genética , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Sobreinfección/inmunología , Linfocitos T/inmunología
13.
Adv Exp Med Biol ; 452: 67-73, 1998.
Artículo en Inglés | MEDLINE | ID: mdl-9889961

RESUMEN

Through experiments in which pro-inflammatory mediators have been neutralized in schistosomeinfected WT and IL-4 -/- mice we have been investigating the nature of the immune response that is required to allow survival during the period of acute disease that accompanies the onset of egg production by the parasitic worms. The developing picture is that of an early pro-inflammatory type-1 like response (characterized by the production of IFN-gamma and TNF-alpha and NO) which in the short term is able to control the deleterious effects on the liver associated with the arrival of the eggs, followed rapidly by a potent egg-induced Th2 response which simultaneously subsumes the role of protecting the liver and downregulates the production of the inflammatory mediators, thereby averting the serious consequence associated with the continued high level production of NO. Current research is directed towards: 1) understanding how pro-inflammatory mediators are protective during schistosomiasis, and 2) elucidating the underlying mechanisms through which the Th response is biased in a Th2 direction following exposure to schistosome eggs.


Asunto(s)
Citotoxicidad Inmunológica , Schistosoma mansoni/inmunología , Esquistosomiasis mansoni/inmunología , Células Th2/inmunología , Animales , Humanos , Interferón gamma/inmunología , Interleucina-4/inmunología , Ratones , Factor de Necrosis Tumoral alfa/inmunología
14.
Parasitol Today ; 14(10): 422-7, 1998 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-17040834

RESUMEN

Of the estimated 200 million people infected with Schistosoma, a subset develop severe life-threatening disease. Adult Schistosoma mansoni are refractory to the immune response and are long-lived, causing chronic exposure to parasite antigen. Although the adult worms themselves are not antigenically inert, it is the parasite eggs that, by accumulating in the liver and traversing the intestinal wall, place a complex series of often-conflicting demands on the host's immune system. In this article, Laura Rosa Brunet, David Dunne and Edward Pearce discuss data from experimental studies in the mouse and field studies in endemic areas that combine to suggest that it is a failure to juggle this immunological conflict that results in severe disease.

15.
J Immunol ; 159(2): 777-85, 1997 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-9218595

RESUMEN

To examine the role of the Th2-type response during schistosomiasis mansoni we compared disease progression in wild type (wt), and Th2-response deficient IL-4(-/-) mice. Whereas wt C57BL/6 mice tolerate infection and develop chronic disease, IL-4(-/-) C57BL/6 animals are highly susceptible, exhibiting severe acute cachexia followed by death. Data point toward morbidity in the IL-4(-/-) C57BL/6 mice being mediated by TNF-alpha, possibly through the uncontrolled production of nitric oxide in target organs such as the ileum. We propose that IL-4 prevents severe disease during schistosomiasis by regulating macrophage activation.


Asunto(s)
Interleucina-4/fisiología , Esquistosomiasis/fisiopatología , Factor de Necrosis Tumoral alfa/fisiología , Animales , Caquexia/fisiopatología , Ratones , Ratones Endogámicos C57BL , Esquistosomiasis/metabolismo , Células Th2/fisiología
16.
Res Microbiol ; 148(5): 437-45, 1997 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-9765822

RESUMEN

To determine whether Lyme disease spirochaetes (Borrelia burgdorferi) within vector ticks (lxodes dammini) sampled from enzootic sites comprise single or mixed populations, we compared their reactivity to a polyclonal rabbit immune serum with that to a battery of monoclonal antibodies (mAb) against OspA, OspB and flagellin. More spirochaetes were recognized by the polyclonal antibody than with the mAbs. Spirochaetes from field-sampled ticks reacted poorly to mAbs against OspB. No such differences in reactivity to polyclonal or monoclonal antibodies were observed for the N40 strain of B. burgdorferi from BSK cultures and infected laboratory-reared vector ticks. We conclude that in nature each tick may be infected by an antigenically heterogeneous mixture of spirochaetes.


Asunto(s)
Variación Antigénica/inmunología , Vectores Arácnidos/microbiología , Grupo Borrelia Burgdorferi/inmunología , Ixodes/microbiología , Animales , Anticuerpos Antibacterianos , Anticuerpos Monoclonales , Antígenos Bacterianos/análisis , Proteínas Bacterianas/análisis , Conejos
18.
Exp Parasitol ; 84(2): 295-9, 1996 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-8932780

RESUMEN

This review focuses on the role of IL-4 in the immune response which develops during infection with the trematode parasite Schistosoma mansoni. The emphasis is on our own recent studies in the mouse model.


Asunto(s)
Interleucina-4/inmunología , Esquistosomiasis mansoni/inmunología , Animales , Linfocitos T CD8-positivos/inmunología , Humanos , Activación de Linfocitos , Ratones , Células Th2/inmunología
19.
Res Microbiol ; 147(9): 739-51, 1996.
Artículo en Inglés | MEDLINE | ID: mdl-9296108

RESUMEN

A Borrelia burgdorferi chromosomal gene encodes a 30-kDa antigen (P30) that has considerable homology with periplasmic substrate-binding proteins of Gram-negative bacteria, and is recognized by antibodies in sera from a subset of patients with Lyme disease and from B. burgdorferi-infected mice. The p30 gene is 801 nucleotides in length and P30 contains 267 amino acids, with a predicted molecular mass of 30 kDa. The P30 amino acid region 36-258 has homology to conserved domains of the oligopeptide permease A of Gram-negative bacteria. Immunofluorescence studies using murine anti-P30 serum suggest that P30 is on the outer surface of B. burgdorferi. P30 expression could be detected in representatives of all 3 subspecies of B. burgdorferi sensu lato, but not in all of the tested strains. Antibodies to P30 were detected in sera of 18 out of 82 patients (22%) with Lyme disease, including individuals with early- or late-stage infection. Although antibodies to P30 are present in the sera of C3H/HeN mice infected with B. burgdorferi for at least 90 days, immunization with recombinant P30 does not protect mice from infection. We conclude that P30 is a putative substrate-binding protein of B. burgdorferi and is immunologically recognized in human and murine Lyme borreliosis.


Asunto(s)
Proteínas de la Membrana Bacteriana Externa/química , Grupo Borrelia Burgdorferi/fisiología , Animales , Anticuerpos/análisis , Proteínas de la Membrana Bacteriana Externa/inmunología , Grupo Borrelia Burgdorferi/inmunología , Proteínas Portadoras , Bacterias Gramnegativas/enzimología , Humanos , Enfermedad de Lyme/inmunología , Proteínas de Transporte de Membrana/química , Ratones , Ratones Endogámicos C3H , Datos de Secuencia Molecular , Alineación de Secuencia , Homología de Secuencia de Aminoácido
20.
J Exp Med ; 183(1): 271-5, 1996 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-8551231

RESUMEN

Borrelia burgdorferi, the spirochetal agent of Lyme disease, is transmitted by Ixodes ticks. A vaccine based on B. burgdorferi outer surface protein (Osp) A protects mice from spirochete infection. Here we report on the expression of OspA on spirochetes inside engorging ticks and relate OspA expression to antispirochetal immunity. Spirochetes in the gut of unfed nymphal ticks were stained by an OspA antibody, whereas in feeding ticks, the majority of spirochetes in the gut and salivary glands did not stain with the antibody. Thus, OspA was not expressed on most spirochetes during transmission from the vector to the vertebrate host. To examine the mechanism of protection afforded by OspA antibody, mice were passively immunized with OspA antibody at different times relative to tick attachment. When OspA antibody was administered to mice before or at the time of tick attachment, spirochetal development events in the vector, such as growth and salivary gland invasion, were blocked and the mice were protected from B. burgdorferi infection. When OspA antibody was administered to mice 48 h after tick attachment, spirochetes persisted in the nymphs and the mice were not protected despite the presence of circulating antibodies in the host as well as in the tick blood meal. Thus, OspA immunity appears to be effective only during a narrow window time at the beginning of the blood meal when antibodies bind to OspA-expressing spirochetes in the tick gut and block transmission from the vector to the host.


Asunto(s)
Antígenos Bacterianos , Antígenos de Superficie/inmunología , Vectores Arácnidos/microbiología , Proteínas de la Membrana Bacteriana Externa/inmunología , Vacunas Bacterianas/inmunología , Ixodes/microbiología , Lipoproteínas , Enfermedad de Lyme/transmisión , Animales , Anticuerpos Antibacterianos/inmunología , Anticuerpos Antibacterianos/uso terapéutico , Vectores Arácnidos/inmunología , Vacunas Bacterianas/uso terapéutico , Grupo Borrelia Burgdorferi/crecimiento & desarrollo , Sistema Digestivo/microbiología , Técnica del Anticuerpo Fluorescente , Inmunoterapia Adoptiva , Ixodes/inmunología , Enfermedad de Lyme/inmunología , Enfermedad de Lyme/prevención & control , Ratones , Ratones Endogámicos C3H , Glándulas Salivales/microbiología
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