RESUMEN
The American cutaneous forms of leishmaniasis include immune-responder individuals with localised cutaneous leishmaniasis (LCL) and non-responder individuals with diffuse cutaneous leishmaniasis (DCL). Patients with intermediate or chronic cutaneous leishmaniasis (ICL) have increased morbidity due to the length of their illness, atypical forms and areas of compromise. In the present study, we evaluated the expression of the leukocyte antigens (CD4, CD8, CLA: cutaneous lymphocyte antigen, CD69, CD83 and CD1a) and cytokines (IFN-gamma, IL-4, IL-10 and TGF-beta 1) in the lesions of patients with ICL (n = 18) using an immunocytochemical procedure. ICL results were compared with the information for LCL (n = 19) and DCL (n = 4). The numbers of CD4+ and CD8+ T cells in ICL were similar to those of LCL lesions, but significantly different (P < or = 0.05) from DCL lesions. LCL lesions have about half the numbers of early activated CD69+ cells as ICL, but most are CLA+ skin homing memory T cells, whereas ICL lesions have the highest number of CD69+ T cells, but about one-third of these cells expressed CLA. This suggests that the granuloma of ICL patients contains many activated T cells that are unprimed to cutaneous-launched antigens, thus contributing to an aberrant immune response. In contrast, DCL granulomas presented the lowest numbers of activated CD69+ and CLA+ cells, associated with the characteristic tolerogenic state of these patients. The immunolocalisation of cytokines showed a mixed cytokine pattern in ICL lesions with many positive cells for IL-10, TGF-beta 1, IL-4 and IFN-gamma, with a preponderance of the first two, and different from the prevalent Th1 and Th2 responses associated with LCL and DCL lesions, respectively. CD1a+ Langerhans cells were decreased (P < or = 0.05) in both ICL (271 +/- 15 cells/mm2) and DCL (245 +/- 19 cells/mm2) as compared to LCL (527 +/- 54 cells/mm2) epidermis. The percentage of IL-10+ epidermal Langerhans cells in ICL (33.69), from the total CD1a+ population, was higher than in LCL (17.45). In addition, fewer CD83+ primed Langerhans cells were present in ICL epidermis. The diminished participation of epidermal Langerhans cells, causing a defective signalling by the epidermis, in ICL lesions may account for the tissue-damaging state observed in these patients.
Asunto(s)
Citocinas/metabolismo , Leishmaniasis Cutánea/fisiopatología , Leucocitos/inmunología , Antígenos CD/metabolismo , Antígenos de Diferenciación de Linfocitos T , Antígenos de Neoplasias , Enfermedad Crónica , Humanos , Inmunofenotipificación , Leishmaniasis Cutánea/patología , Leishmaniasis Cutánea Difusa/patología , Leishmaniasis Cutánea Difusa/fisiopatología , Leishmaniasis Mucocutánea/patología , Leishmaniasis Mucocutánea/fisiopatología , Glicoproteínas de Membrana/análisisRESUMEN
American cutaneous leishmaniasis is characterized by a spectrum of clinical manifestations. These include localized, often self-healing single lesions, intermediate forms which frequently produce mucosal lesions and often show exaggerated delayed-type hypersensitivity (DTH), and the rare diffuse cutaneous leishmaniasis in which no reaction of protective cell-mediated immunity or DTH can be demonstrated. Clinical, pathological and immunological studies have begun to unravel some of the mechanisms associated with different disease manifestations, dependent on complex interactions between the host immune response, measured in terms of indices including lymphocyte subsets and lymphokines in vitro and within active lesions, and different species of Leishmania.
Asunto(s)
Leishmaniasis Cutánea/inmunología , Piel/inmunología , Animales , Antígenos de Protozoos/inmunología , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Hipersensibilidad Tardía/inmunología , Leishmania mexicana/inmunología , Leishmaniasis Cutánea/patología , Leishmaniasis Cutánea Difusa/inmunología , Leishmaniasis Mucocutánea/inmunología , Activación de Linfocitos/inmunología , Masculino , Piel/patologíaRESUMEN
En un ensayo clínico controlado, con evaluación a ciegas y asignación al azar, se ha evaluado la eficacia terapéutica de una combinación de B.C.G. con promastigotes de L.Mexicana amazonensis muertos por calor (Inmunoterapia) en comparación con Antimoniaco de Meglumine (Quimioterapia) y un tercer grupo vacunado con B.C.G. solamente, con un total de 171 pacientes de Leishmaniasis Cutánea localizada (99 Inmunoterapia, 46 Quimioterapia y 26 con BCG). Los resultados obtenidos son comparables en los dos primeros grupos, tanto en el porcentaje de curación (más del 95% a las 32 semanas) como en el tiempo promedio de curación (alrededor de 17 semanas, en cambio en el grupo con BCG solamente los porcentajes de curación son muy bajos (38,5% a las 32 semanas) y el tiempo promedio de curación mucho más prolongado (26 semanas). Los efectos secundarios fueron leves e infrecuentes (menos del 5%) en inmunoterapia y con BCG solo, pero muy frecuente (48%) y severos en quimioterapia. Resultados preliminares indican así mismo buena eficacia terapéutica de la inmunoterapia en pacientes cutáneos y mucosos del área intermedia del espectro clínico-inmunológico y en pacientes con L.Cutánea Difusa (LCD). en este trabajo se discuten los fundamentos de la inmunoterapia en Leishmaniasis en base al espectro de deficiencias de inmunidad celular y se plantean las perspectivas de la inmunoprofilaxis en base a estos conceptos
Asunto(s)
Humanos , Masculino , Femenino , Inmunoterapia , Leishmaniasis/inmunología , Leishmaniasis/terapiaRESUMEN
Conventional vaccination is oriented toward the prevention of disease in individuals capable of developing normal immune responses. A new model of vaccination employing two microorganisms has been described for the correction of variable degrees of antigen-specifit deficiency in the development of effective cell-mediated immunity in two diseases, leprosy and cutaneous leishmaniasis, both of which are characterized by a spectrum of clinical manifestations. A schematic representation of the immunologic defect in the severe and progressive forms of these diseases and a possible mechanism for its correction using this vaccine model are presented. Immunotherapeutic and immunoprophylactic applications of the model are described, with particular reference to recent experience in the immunotherapy of localized cutaneous leishmaniasis. The efficacy, virtual absence of secondary effects, ease of administration and low cost of this therapeutic modality indicate that it offers an important option or field use in endemic of leishmaniasis
Asunto(s)
Humanos , Inmunoterapia , Leishmaniasis/inmunología , Lepra/inmunologíaRESUMEN
Mechanisms possibly involved in the regulation of the immune response were evaluated in 49 patients with American cutaneous leishmaniasis (ACL). The patients were classified on the basis of clinical and histopathological criteria as suffering localized (LCL), mucocutaneous (MCL) or diffuse (DCL) forms of the disease. A significant leishmanial antigen-induced suppression of in vitro mitogen responsiveness was demonstrated in the DCL group, but not in the other two diseases states. Lack of suppressive activity was particularly evident in MCL, this being the group that presented the highest in vivo and in vitro reactivity to the parasite antigens. In fact, a significant inverse correlation was found between the degree of suppression and the antigen-induced lymphocyte proliferative response. In contrast, a mixture of mononuclear cells from MCL patients and normal subjects showed higher that expected responses to mitogen, while this increase was not observed in co-cultures of DCL and normal mononuclear cells. Due to their possible modulatory influences, circulating immune complexes were also evaluated in these patient groups, higher levels being found in MCL and DCL patients than in either LCL or controls. The possible mechanisms involved in the regulation of the immune response to the protozoan in the complex disease spectrum of ACL are discussed in relation to anergy in DCL and hyperresponsiveness in MCL.
Asunto(s)
Masculino , Femenino , Humanos , Antígenos/inmunología , Activación de Linfocitos , Complejo Antígeno-Anticuerpo/análisis , Concanavalina A/farmacología , División Celular , Fitohemaglutininas/farmacología , Leishmania/inmunología , Leishmaniasis Mucocutánea/inmunología , Leishmaniasis/inmunologíaRESUMEN
The in vitro and in vivo cellular immune reactivity of 49 patients with American cutaneous leishmaniasis (ACL) was evaluated using mitogens and parasite antigens. Patients were examined before treatment and were classified on the basis of clinical and histopathological criteria as suffering localized cutaneous leishmaniasis (LCL, 32 patients) or mucocutaneous leishmaniasis (MCL, 11 patients). A small group (6 patients) of treated diffuse cutaneous leishmaniasis (DCL) patients was also examined. The lymphocyte proliferative responses to PHA were significantly lower than those of controls (87 individuals, from either endemic or nonendemic zones) in LCL, and particularly MCL. Con A responses were, however, effectively normal in these patients. Both in vivo and in vitro cellular immune responses to leishmanial antigens were significantly greater in MCL and LCL patients than in the controls, the intensity of the reactions being by far the greatest in MCL. DCL patients demonstrated a complete absence of specific immune responsiveness both in vivo and in vitro. The significance of these results in the mechanisms leading to the resolution of the infection or production of pathologic lesions is discussed.
Asunto(s)
Leishmaniasis Mucocutánea/inmunología , Leishmaniasis/inmunología , Adolescente , Adulto , Antígenos/inmunología , Enfermedad de Chagas/inmunología , Femenino , Helmintiasis/diagnóstico , Humanos , Hipersensibilidad Tardía/diagnóstico , Inmunidad Celular , Leishmaniasis/diagnóstico , Leishmaniasis/epidemiología , Leishmaniasis Mucocutánea/diagnóstico , Leishmaniasis Mucocutánea/epidemiología , Activación de Linfocitos , Masculino , Persona de Mediana Edad , Pruebas Cutáneas , VenezuelaRESUMEN
Diffuse cutaneous leishmaniasis, with its characteristic diffusion of lesions, great abundance of parasites, anergy to skin tests with the specific antigen and resistance to treatment, has been described as a disease produced by a special strain of Leishmania, L. pifanoi. Our concept is that this form of leishmaniasis is due, not to a different type of parasite, but to an immunological defect of the human host, which makes him respond with tese special clinical and parasitological manifestations. The basis fou our beleif is: (1) epidemiologically, the disease appears as isolated saces in endemic areas; (2) accidental inoculation of a laboratory technicain with a strain taken from a animal.