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Induction of humoral immune responses in the genital tract
Abstracts / Journal of Reproductive Immunology 81 (2009) 113–175
iodide staining of nuclei of dead cells. This was applied for evaluation of the toxic effect of oxidative stress.
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antigen delivery systems should be pursued to design immunization protocols effective in the induction of humoral responses in the genital tract.
doi:10.1016/j.jri.2009.06.156 L31 Induction of humoral immune responses in the genital tract J. Mestecky a,∗ , Z. Moldoveanu a , R.C. Alexander a , M. Raska b a
Department of Microbiology, University of Alabama at Birmingham, Birmingham, USA b School of Medicine, Palacky University, Olomouc, Czech Republic Induction of protective humoral immune responses in the secretions of the female and male genital tracts is a desirable goal in the prevention of sexually transmitted diseases, including HIV, and also as an approach to fertility control by antibody-mediated mechanisms. However, distinct immunization strategies that are applicable to the immunologically unique genital tract must be considered. It has been well established that local infection or immunization with microbial antigens is ineffective in the induction of such local or generalized humoral responses. In contrast to other typical mucosal tissues, such as the intestine, antibodies from the circulation contribute (with variations during the menstrual cycle in females) significantly to the pool of antibodies in both male and female genital tract secretions. Consequently, circulating antibodies, mostly of the IgG isotype, are found in genital tract secretions after systemic immunization. Importantly, the intranasal application of a variety of antigens in several animal species effectively induced humoral responses in immunized individuals. Based on an experiment limited to a single bacterial antigen, this immunization strategy may also be effective in humans. DNA immunization represents a novel approach highly effective in the induction of both humoral and cellular responses in mice; immune responses in other species, including humans, are unimpressive. However, targeting DNA to cells and tissues endowed with a high proteosynthetic potential (e.g. epithelial cells or hepatocytes) results in the production of high levels of properly folded and glycosylated antigens, which in turn induce vigorous immune responses. A combination of systemic DNA immunization with intranasal application of viral antigens induced high levels of antibodies in genital tract secretions. Additional studies of various immunization routes and their combinations, as well as the critical evaluation of different
doi:10.1016/j.jri.2009.06.157 L32 Inflammatory reaction and implantation: the new entries PTX3 and D6 C. Garlanda a , Y. Martinez de la Torre a , M. Nebuloni b , M. Locati a,c a
Istituto Clinico Humanitas IRCCS, Rozzano, Italy Unit, L. Sacco Department of Clinical Sciences, University of Milan, Milan, Italy c Institute of General Pathology, University of Milan, Milan, Italy b Pathology
Successful embryonic implantation implies anchoring the conceptus in the maternal uterine wall, establishing a vascular supply to enable optimal growth and development of the conceptus, and promoting tolerance of fetal alloantigens encoded by paternal genes. To achieve these goals, complex molecular dialogues take place among the maternal endometrium, the conceptus, and the placenta, which are mediated by several factors, including hormones, growth factors, cytokines, chemokines, adhesion molecules, extracellular matrix components, and matrix-degrading enzymes. This fetal–maternal interaction creates a local inflammatory response and a state of systemic inflammation, which is revealed by leukocytosis, endothelium activation, increased activity of innate immune cells, and increased levels of inflammatory cytokines and chemokines. The enriched cytokine milieu associated to implantation is likely to control trophoblast migration and differentiation, leukocyte influx and activation, complement activation, as well as angiogenic and angiostatic processes in the implantation site. Finally, these mediators play a key role in tuning the immune responses to protect the fetus from infections as well as from maternal rejection. The role of proinflammatory networks activated in implantation will be discussed. In particular, emphasis will be put on two new players involved in regulating inflammation at the maternal–fetal interface: the long pentraxin PTX3 and the decoy receptor for inflammatory chemokines D6. In particular, we provide evidence for a role of the long pentraxin PTX3 in normal female fertility, in processes which range from cumulus oophorus expansion (Salustri et al., 2004; Scarchilli et al., 2007), decidualization and implantation (Tranguch et al., 2007; Popovici et al., 2008), extracellular matrix assembly, angiogene-
iodide staining of nuclei of dead cells. This was applied for evaluation of the toxic effect of oxidative stress.
127
antigen delivery systems should be pursued to design immunization protocols effective in the induction of humoral responses in the genital tract.
doi:10.1016/j.jri.2009.06.156 L31 Induction of humoral immune responses in the genital tract J. Mestecky a,∗ , Z. Moldoveanu a , R.C. Alexander a , M. Raska b a
Department of Microbiology, University of Alabama at Birmingham, Birmingham, USA b School of Medicine, Palacky University, Olomouc, Czech Republic Induction of protective humoral immune responses in the secretions of the female and male genital tracts is a desirable goal in the prevention of sexually transmitted diseases, including HIV, and also as an approach to fertility control by antibody-mediated mechanisms. However, distinct immunization strategies that are applicable to the immunologically unique genital tract must be considered. It has been well established that local infection or immunization with microbial antigens is ineffective in the induction of such local or generalized humoral responses. In contrast to other typical mucosal tissues, such as the intestine, antibodies from the circulation contribute (with variations during the menstrual cycle in females) significantly to the pool of antibodies in both male and female genital tract secretions. Consequently, circulating antibodies, mostly of the IgG isotype, are found in genital tract secretions after systemic immunization. Importantly, the intranasal application of a variety of antigens in several animal species effectively induced humoral responses in immunized individuals. Based on an experiment limited to a single bacterial antigen, this immunization strategy may also be effective in humans. DNA immunization represents a novel approach highly effective in the induction of both humoral and cellular responses in mice; immune responses in other species, including humans, are unimpressive. However, targeting DNA to cells and tissues endowed with a high proteosynthetic potential (e.g. epithelial cells or hepatocytes) results in the production of high levels of properly folded and glycosylated antigens, which in turn induce vigorous immune responses. A combination of systemic DNA immunization with intranasal application of viral antigens induced high levels of antibodies in genital tract secretions. Additional studies of various immunization routes and their combinations, as well as the critical evaluation of different
doi:10.1016/j.jri.2009.06.157 L32 Inflammatory reaction and implantation: the new entries PTX3 and D6 C. Garlanda a , Y. Martinez de la Torre a , M. Nebuloni b , M. Locati a,c a
Istituto Clinico Humanitas IRCCS, Rozzano, Italy Unit, L. Sacco Department of Clinical Sciences, University of Milan, Milan, Italy c Institute of General Pathology, University of Milan, Milan, Italy b Pathology
Successful embryonic implantation implies anchoring the conceptus in the maternal uterine wall, establishing a vascular supply to enable optimal growth and development of the conceptus, and promoting tolerance of fetal alloantigens encoded by paternal genes. To achieve these goals, complex molecular dialogues take place among the maternal endometrium, the conceptus, and the placenta, which are mediated by several factors, including hormones, growth factors, cytokines, chemokines, adhesion molecules, extracellular matrix components, and matrix-degrading enzymes. This fetal–maternal interaction creates a local inflammatory response and a state of systemic inflammation, which is revealed by leukocytosis, endothelium activation, increased activity of innate immune cells, and increased levels of inflammatory cytokines and chemokines. The enriched cytokine milieu associated to implantation is likely to control trophoblast migration and differentiation, leukocyte influx and activation, complement activation, as well as angiogenic and angiostatic processes in the implantation site. Finally, these mediators play a key role in tuning the immune responses to protect the fetus from infections as well as from maternal rejection. The role of proinflammatory networks activated in implantation will be discussed. In particular, emphasis will be put on two new players involved in regulating inflammation at the maternal–fetal interface: the long pentraxin PTX3 and the decoy receptor for inflammatory chemokines D6. In particular, we provide evidence for a role of the long pentraxin PTX3 in normal female fertility, in processes which range from cumulus oophorus expansion (Salustri et al., 2004; Scarchilli et al., 2007), decidualization and implantation (Tranguch et al., 2007; Popovici et al., 2008), extracellular matrix assembly, angiogene-