RESUMO
Immunoglobulin G (IgG) has covalently linked a sugar chain in the crystallizable fragment (Fc). This structure consists of double stranded glycosidic complexes with a high degree of heterogeneity that contribute to define the affinity to their specific receptors, and partly determine their biological activity. Recently was identified an anti-inflammatory mechanism mediated by IgG based on their different alternatives of Fc glycosylation and their interaction with the specific adhesion receptor of dendritic cells (DC-SIGN). This mechanism has clinical and therapeutic implications in autoimmune diseases. The objective of this review is to describe the biochemical structure of sugars associated to the Fc of IgG and its variants in relation to specific functions and pathogenicity, particularly in tuberculosis, in which may also have therapeutic implication.
Assuntos
Anticorpos/química , Glicoproteínas/química , Processamento de Proteína Pós-Traducional , Anticorpos/imunologia , Anticorpos/metabolismo , Afinidade de Anticorpos , Citotoxicidade Celular Dependente de Anticorpos , Reações Antígeno-Anticorpo , Doenças Autoimunes/imunologia , Doenças Autoimunes/metabolismo , Sequência de Carboidratos , Moléculas de Adesão Celular/metabolismo , Glicoproteínas/imunologia , Glicoproteínas/metabolismo , Glicosilação , Humanos , Fragmentos Fc das Imunoglobulinas/química , Fragmentos Fc das Imunoglobulinas/metabolismo , Imunoglobulina G/química , Imunoglobulina G/imunologia , Imunoglobulina G/metabolismo , Infecções/imunologia , Lectinas Tipo C/metabolismo , Modelos Moleculares , Dados de Sequência Molecular , Polissacarídeos/química , Conformação Proteica , Mapeamento de Interação de Proteínas , Receptores de Superfície Celular/metabolismo , Receptores Fc/química , Receptores Fc/metabolismo , Relação Estrutura-AtividadeRESUMO
The protective effect of human gamma globulins on Mycobacterium tuberculosis infection was evaluated in a mouse model of intratracheal infection. Animals receiving human gamma globulins intranasally, 2h before intratracheal challenge showed a significant decrease in lung bacilli load compared to non-treated animals in different time intervals of up to 2 months after challenge. The same effect was obtained when M. tuberculosis was pre-incubated with the gamma globulin before challenge. The protective effect of the gamma-globulin formulation was abolished after pre-incubation with M. tuberculosis. These results suggest a potential role of specific antibodies in the defence against mycobacterial infections.
Assuntos
Fatores Imunológicos/administração & dosagem , Mycobacterium tuberculosis/efeitos dos fármacos , Tuberculose Pulmonar/prevenção & controle , gama-Globulinas/administração & dosagem , Administração Intranasal , Animais , Contagem de Colônia Microbiana , Fatores Imunológicos/imunologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Mycobacterium tuberculosis/imunologia , Mycobacterium tuberculosis/isolamento & purificação , Tuberculose Pulmonar/microbiologia , gama-Globulinas/imunologiaRESUMO
Mycobacterium tuberculosis is a facultative intracellular pathogen for which cell-mediated immunity is considered the major component of the immune response. For many decades, the prevailing scientific view has been the antibodies have little or no role in modifying the course of M. tuberculosis infection. In recent years, several studies have challenged this dogma, and there is a body of evidence that supports a role of antibodies against M. tuberculosis. In the present work, we evaluated the protective activity of two monoclonal antibodies (TBA61 and TBA84). Here, we chose the intratracheal model of pulmonary infection to evaluate bacterial load and morphometric and histological changes in the lungs of treated mice. Data obtained revealed the reduction of bacterial load and milder morphometric and histopathological changes in mice treated with TBA61 at 21 days post-infection with M. tuberculosis H37Rv compared to those treated with TBA84 and control mice. These results allow continuing exploring the potential use of monoclonal antibodies as prophylactic and therapeutic agents against intracellular pathogens such as M. tuberculosis.
Assuntos
Anticorpos Antibacterianos/imunologia , Anticorpos Monoclonais/imunologia , Imunoglobulina A/imunologia , Mycobacterium tuberculosis/imunologia , Tuberculose Pulmonar/imunologia , Animais , Anticorpos Antibacterianos/administração & dosagem , Anticorpos Monoclonais/administração & dosagem , Contagem de Colônia Microbiana , Feminino , Imunoglobulina A/administração & dosagem , Pulmão/microbiologia , Pulmão/patologia , Camundongos , Camundongos Endogâmicos BALB C , Mycobacterium tuberculosis/patogenicidadeRESUMO
Convencionalmente se asume que la defensa del hospedero contra Mycobacterium tuberculosis se basa en los mecanismos de inmunidad celular exclusivamente y se descarta el papel de los anticuerpos en la protección. En este trabajo se analizan evidencias recientes que retan este dogma y sugieren la importancia de considerar la manipulación de la respuesta inmune humoral como una alternativa en la investigación de vacunas contra la tuberculosis(AU)
Assuntos
Mycobacterium tuberculosis/patogenicidade , Anticorpos/imunologiaRESUMO
The effect of the administration of a commercial preparation of human gamma globulins has been evaluated in a mouse model of intranasal infection with BCG. First, we demonstrated the passage of specific antibodies to saliva and lung lavage following the intranasal or intraperitoneal administration to mice of human gamma globulins. This treatment of mice inhibited BCG colonization of the lungs (p < 0.01). A similar inhibitory effect was observed after infection of mice with gamma globulin opsonized BCG organisms (p < 0.01). These results are relevant for the development of new strategies for the control and treatment of tuberculosis.