The protective role of antibody responses during Mycobacterium tuberculosis infection.
Tuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb) is one of the most important infectious diseases globally. Immune effector mechanisms that lead to protection or development of clinical disease are not fully known. It is generally accepted that cell-mediated immunity (CMI) plays a pivotal role in controlling Mtb infection, whereas antibody responses are believed to have no protective role. This generalization is based mainly on early classical experiments that lacked standard protocols, and the T helper type 1 (Th1)/Th2 paradigm. According to the Th1/Th2 paradigm Th1 cells protect the host from intracellular pathogens, whereas Th2 cells protect form extracellular pathogens. During the last two decades, the Th1/Th2 paradigm has dominated not only our understanding of immunity to infectious pathogens but also our approach to vaccine design. However, the last few years have seen major discrepancies in this model. Convincing evidence for the protective role of antibodies against several intracellular pathogens has been established. Studies of B cell-deficient mice, severe combined immunodeficiency (SCID) mice, passive immunization using monoclonal (mAb) and polyclonal antibodies and immune responses against specific mycobacterial antigens in experimental animals reveal that, in addition to a significant immunomodulatory effect on CMI, antibodies play an essential protective role against mycobacterial infections. In this review, our current understanding of the essential role of antibodies during Mtb infections, limitations of the Th1/Th2 model and the unfolding interdependence and mutual regulatory relationships between the humoral and CMI will be presented and discussed.
Abebe
F
F
University of Oslo, Faculty of Medicine, Institute of General Practice and Community Medicine, Section for International Health, Oslo, Norway. fekadu.abebe@medisin.uio.no
Bjune
G
G
D000818:Animals; D000917:Antibody Formation; D001402:B-Lymphocytes / Q000276:immunology; D016207:Cytokines / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular; D051379:Mice; D016513:Mice, SCID; D023421:Models, Animal; D018448:Models, Immunological; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D032581:Tuberculosis Vaccines
D016207:Cytokines; D032581:Tuberculosis Vaccines