Aspectos imunológicos da hanseníase / Immunological aspects of leprosy

A distribuiçäo espectral das formas clínicas da hanseníase tem sido associada a alteraçöes imunológicas do hospedeiro, frente ao M. leprae. Foi verificado que, no pólo de maior suscetibilidade, hanseníase virchoviana, apresenta depressäo da resposta imune celular, associada ao aumento da produçäo de citocinas supressoras (Il-4 e TGFß) e reduçäo dos níveis de citocinas ativadoras da resposta imune (TNFalfa, IL-1 e IFNgama). Há, ainda, menor produçäo de elementos responsáveis pela oxidaçäo intracelular, como intermediários do nitrogênio (RN), avaliada pela expressäo da enzima NO sintase induzida (iNOS). Por outro lado, no pólo de resistência, hanseníase tuberculóide, näo foram detectadas as citocinas supressoras, em contraste com elevadas concentraçöes de TNFalfa e IL-1, citocinas indutoras da reaçäo inflamatória.

Immunological status of ENL (erythema nodosum leprosum) patients: its relationship to bacterial load and levels of circulating IL-2R

Dados recentes sugerem que o curso clinico dos estados reacionais na lepra esta estritamente relacionado a liberacao local ou sistemica de citocinas. Neste estudo, pacientes com ENL (erythema nodosum leprosum) foram agrupadas segundo a intensidade de seus sintomas clinicos. Os aspectos clinicos e imunologicos do ENL e os efeitos desses parametros na carga bacilar foram estabelecidos em conjuncao com a resposta imune in vitro desses pacientes, a antigenos microbacterianos. Em 10 de 17 pacientes testados, o indice bacteriano (IB) foi reduzido em pelo menos 1 log desde o diagnostico da lepra ate o aparecimento do primeiro episodio reacional, comparado a uma reducao esperada de 0.3 log no grupo reacional no mesmo periodo de MDT (multidrogaterapia)...

Eritema nodoso hansênico: análise comparativa do quadro histopatológico pelas técnicas de rotina e imunofluorescência / Erythema nodosum leprosum: comparative analysis of histopathologic situation by routine and immunofluorescence technique

Com a finalidade de investigar a participaçao dos imunocomplexos (Ic) na reaçao de Eritema Nodoso Hansênico (ENH), fragmentos teciduais de 22 pacientes hansenianos reacionais foram avaliados através da técníca de imunofluorescência direta (IFD) em associaçao com técnicas histopatológicas de rotina. Os resultados demonstraram a presença de Ic em vasos e zona de membrana basal da junçao dermo-epidérmica (ZMB). A presença de Ic em vasos do derma profundo e tecido celular subcutâneo em correspondência com alteraçoes vistas sob a forma de vasculites alterativas, exsudativas e necrotizantes sugerem envolvimento destes complexos no ENH.

Studies of human leprosy lesions in situ using suction-induced blisters: cell changes with IgM antibody to PGL-1 and interleukin-2 receptor in clinical subgroups of erythema nodosum leprosum.

To examine the immunopathogenesis of type 2 erythema nodosum leprosum (ENL) reactions in leprosy, we studied cellular and soluble immunologic components of skin lesions in 57 patients with reactions (19 acute ENL and 38 chronic ENL), 61 active patients without reactions, and 33 control patients whose leprosy had been treated and cured. Cells, IgM antibody to PGL-1 and Tac peptide levels were obtained from fluid aspirated from blisters induced by suction directly over representative skin lesions. During ENL reactions: a) the lesions in chronic ENL showed a decreased number of CD8+ (T-suppressor) cells and increased helper/suppressor ratio as compared to those in acute ENL and non-reactional leprosy; b) Tac peptide and IgM antibody to PGL-1 levels were elevated in the chronic ENL lesions; c) and systemic administration of corticosteroids appeared to cause a reduction in the intralesional CD4+ cell population and IgM antibody to PGL-1 but did not change CD8+ cell population and the levels of Tac peptide in the lesions. The elevated levels of Tac peptide were localized in the skin lesions while increased levels of IgM anti-PGL-1 seemed to be filtered from the peripheral blood. We conclude that spontaneous lymphocyte activation in situ, primarily of decreased CD8+ and relatively increased CD4+ cells, are important features of chronic, recurrent ENL reactions and may be an intermittent or cyclic phenomenon during the reaction. Understanding the mechanisms of these spontaneous changes in immunity in leprosy will enlarge our knowledge of reactions and of the underlying determinants of delayed type hypersensitivity and cell-mediated immunity in leprosy, which in turn will allow us to realize the potential for artificially manipulating these responses as proposed with vaccines or immunotherapy.

Sistema monocítico-macrofágico y mycobacterium leprae: su importancia en la interpretación patogénica de las distintas formas clínico-patológicas de la Lepra y de las reacciones leprosas / Monocytic-macrophagic system and mycobacterium leprae

Se realiza una revisión de la patogenia de la Lepra (Hanseniasis), en sus vinculaciones con el "sistema monocítico-macrofágico y se efectúa el estudio histopatológico, histoquimico (lipídico) y con microscopía electrónica de cuatro enfermos de Lepra, dos lepromatosos ( sin y con eritema nudoso) y otros dos dimorfos ("Borderline"). Se concluye que: 1) La Lepra presenta sus manifestaciones clínico-patológicas más ostensibles, en vinculación con lesiones del "sistema monocítico-macrofágico". 2)Existen distintos comportamientos de los macrófagos frente al mycobacterium leprae" a)en personas Mitsuda positivos se puede demostrar el predominio de "macrófagos lisadores del M.leprae" con muerte y desaparición de los bacilos; b)en individuos Mitsuda-negativos predominan los "magrófagos no lisadores del M.leprae",que también producen la muerte de los bacilos, pero con persistencia de la "envoltura lipídica bacilar", que se deposita en las vacuolas de los virchowcitos; y c)en enfermos Mitsuda-negativos, luego de formado el "Granuloma virchowiano", se desarrollan los "macrófagos lisadores de las células de Virchow" que permitirían el recambio celular de los virchowitos. 3)Los "macrófagos lisadores del M.leprae" obtienen información antigénica del "bacilo aislado" que pueden transmitir al sistema de inmunidad celular, cuyos linfocitos T activados generan los "granulomas epitelioides con células de Langhans" (granulomas tuberculoides), de la Lepra tuberculoide. 4) Los "macrófagos no lisadores del M.leprae" no obtendrían información antigénica adecuada y no tendrían capacidad para estimular ningún sistema inmunológico (celular, o humoral), originando los "granulomas virchowianos" de la Lepra lepromatosa 5)Luego del envejecimiento y muerte de los vinchowcitos, los "macrófagos lisadores de las celulas de Virchow" obtendrían información antigénica de los "bacilos degenerados asociados a lípidos y glucoproteinas citoplasmáticas", con capacidad de estimulación del sistema inmunológico humoral cuyos linfocitos B activados generarían anticuerpos complejos: a)contra bacilos ubicados en los virchowcitos en la Reacción leprosa tipo 2 (eritema nudoso leprótico); b) contra la pared de vasos en la reacción leprosa tipo 3(fenómeno de Lucio); y c)contra tejidos del huésped (enfermedad autoagresiva hanseniana-Azulay). 6)En la lepra no existiría "polaridad inmunológica" en los períodos iniciales de la instalación de la enfermedad, pero parecería secundariamente a la formación del "granulo

The effect of tetanus toxoid in leprosy patients.

Since cases of lepra reaction following smallpox vaccination and BCG vaccination had been reported the effect of tetanus immunisation on leprosy patients (whether it may provoke a lepra reaction or not) was studied. Three doses of purified tetanus toxoid (one ml initially, one ml after six weeks and one ml after six months) were given to 357 leprosy patients and 60 patients living in the same environ were followed as controls. The antibody response following immunisation was followed in six lepromatous leprosy patients using toxin antitoxin neutralisation test at the Lf/1000 level in mice and in three of them the antibody titre of leprosy patients rose to satisfactory level. The number of lepra reactions in these patients was monitored for nine months (two months before vaccination, during the six months period of vaccination and one month after the last dose of vaccine). There was no significant rise in the number of patients with reaction following the vaccination.

Serum immune complexes in erythema nodosum leprosum reactions of leprosy.

Serum estimations of immunoglobulins, complement components and their presence in circulating immune complexes were carried out in 39 Lepromatous, 44 ENL and 22 Post ENL leprosy patients. Serum IgG, IgA, IgM, C3 and C4 levels were determined by single radial immunodiffusion. Serum immune complexes were precipitated with Polyethylene Glycol (PEG) and IgG, IgA, IgM, C3 and C4 were estimated by single radial immunodiffusion and expressed as % of precipitation of their serum level. Decreased IgG, IgM; increased IgA and C3; and no change in C4 levels are observed in ENL than Lepromatous and Post ENL patients. However, a gradual insignificant reduction of IgG, IgA, and IgM was found from Lepromatous to ENL and Post ENL patients in the PEG-precipitates. Similarly, C3 and C4 was found reduced insignificantly in ENL than Lepromatous and Post ENL patients. The significance of these estimations in relation to immune status of ENL reactions are discussed.

Tr, T mu and B lymphocytes in erythema nodosum leprosum reactions of leprosy.

Enumeration of sub-population of T cells with receptors for Fc portion of Ig G (Tr) and Fc portion of Ig M (Tu) and B lymphocytes in the peripheral blood of 39 Lepromatous, 44 ENL and 22 Post ENL patients were undertaken. ENL patients showed significant decreased Tr cell percentage than Lepromatous and Post ENL patients. Although T mu cell percentage was lowered in ENL patients, a relatively elevated T mu/Tr ratio was found than Lepromatous and Post ENL patients indicating elevation of helper activity in ENL. B cells did not register any change in the three stages.

Erythema nodosum leprosum (ENL) in histoid leprosy.

The morphological features of ENL, occurring in histoid leprosy are described. Its infrequent occurrence has been emphasised. The possible immunopathogenesis of its occurrence in histoid leprosy is briefly outlined.