An age-related decline in immune responses in the elderly results in greater susceptibility to infection and reduced responses to vaccination. This decline in immune function affects both innate and adaptive immune systems. A meeting of experts in immunology and gerontology in Paris, France, in April 2008, considered current understanding of immunosenescence and its clinical consequences. Essential features of immunosenescence include: reduced natural killer cell cytotoxicity on a per cell basis; reduced number and function of dendritic cells in blood; decreased pools of naive T and B cells; and increases in the number of memory and effector T and B cells. In particular, an accumulation of late differentiated effector T cells, commonly associated with cytomegalovirus infection, contributes to a decline in the capacity of the adaptive immune system to respond to novel antigens. Consequently, vaccine responsiveness is compromised in the elderly, especially frail patients. Strategies to address the effects of immunosenescence include ensuring that seroprotective antibody levels against preventable infectious diseases are maintained throughout adulthood, and improving diet and exercise to address the effects of frailty. New vaccines are being developed, such as intradermal and high-dose vaccines for influenza, to improve the efficacy of immunization in the elderly. In the future, the development and use of markers of immunosenescence to identify patients who may have impaired responses to vaccination, as well as the use of end-points other than antibody titers to assess vaccine efficacy, may help to reduce morbidity and mortality due to infections in the elderly.

Reactivation of latent human cytomegalovirus (HCMV) following allogeneic transplantation is a major cause of morbidity and mortality and predisposes to severe complications, including superinfection by Aspergillus species (spp). Antimicrobial polypeptides, including defensins and mannan-binding lectin, are known to block viral fusion by cross-linking sugars on cell surface. Pentraxin 3 (PTX3), a member of the long pentraxin family, successfully restored antifungal immunity in experimental hematopoietic transplantation. We assessed here whether PTX3 binds HCMV and murine virus (MCMV) and the impact on viral infectivity and superinfection in vivo. We found that PTX3 bound both viruses, reduced viral entry and infectivity in vitro, and protected from MCMV primary infection and reactivation as well IntroductionHuman cytomegalovirus (HCMV), a member of the Herpesviridae family, is a ubiquitous opportunistic pathogen that has an intimate lifelong relationship with its human host and establishes latency after clearance of primary infection. 1-3 Reactivation of latent virus following allogeneic transplantation immune responses results in progressive tissue damage manifesting as overt HCMV disease or complications of this infection, including acute and chronic graft rejection, graft-versus-host disease, and superinfection by other viruses, bacteria, and fungi, particularly Aspergillus species (spp). 3 Efforts have focused on the development of adoptive immunotherapeutic strategies to hasten host immune reconstruction, and cellular immunotherapy appears to be an attractive approach. 4,5 The immune control of murine CMV (MCMV) infection requires elements from both innate and adaptive immune systems. [6][7][8] Through the participation of members of the Toll-like receptors (TLRs) 9-11 and interferon (IFN) regulatory factor 3 (IRF) families, IRF3 in particular, 12,13 MCMV induces early dendritic cell (DC)-dependent type I IFN and interleukin-12 (IL-12) responses essential for mouse resistance to MCMV. 10,11,[14][15][16] The TLR9/ MyD88 signaling pathway mediates antiviral cytokine responses by plasmacytoid DCs (pDCs) that, through their unique capacity to secrete IFN-␣, and to a lesser extent IL-12 and other innate cytokines, are a cornerstone in the initiation of both innate and adaptive immune responses to MCMV. [15][16][17][18][19] However, conventional CD11b ϩ DCs also produce IFN-␣ independently of TLR9 and MyD88. 10,20 In addition to directly interfering with viral replication through ubiquitous cellular mechanisms, IFN-␣ controls natural killer (NK) cell cytotoxic activity 15 and regulates T-cell functions by activating classical DCs to more efficiently present antigens (Ags). 15 IL-12 and IL-18 secretion are instead required to prime a strong NK cell-dependent IFN-␥ response, 17,21,22 a process that is essential to counteract MCMV infection in the liver, in contrast to a perforin-dependent mechanism in the spleen. 23 Pentraxin 3 (PTX3) is a member of a superfamily of conserved proteins characterized by a cyclic mul...

BackgroundA common pattern emerging from several studies evaluating the impact of the 2009 A/H1N1 pandemic influenza (A/H1N1pdm) conducted in countries worldwide is the low attack rate observed in elderly compared to that observed in children and young adults. The biological or social mechanisms responsible for the observed age-specific risk of infection are still to be deeply investigated.MethodsThe level of immunity against the A/H1N1pdm in pre and post pandemic sera was determined using left over sera taken for diagnostic purposes or routine ascertainment obtained from clinical laboratories. The antibody titres were measured by the haemagglutination inhibition (HI) assay. To investigate whether certain age groups had higher risk of infection the presence of protective antibody (≥1∶40), was calculated using exact binomial 95% CI on both pre- and post- pandemic serological data in the age groups considered. To estimate age-specific susceptibility to infection we used an age-structured SEIR model.ResultsBy comparing pre- and post-pandemic serological data in Italy we found age- specific attack rates similar to those observed in other countries. Cumulative attack rate at the end of the first A/H1N1pdm season in Italy was estimated to be 16.3% (95% CI 9.4%-23.1%). Modeling results allow ruling out the hypothesis that only age-specific characteristics of the contact network and levels of pre-pandemic immunity are responsible for the observed age-specific risk of infection. This means that age-specific susceptibility to infection, suspected to play an important role in the pandemic, was not only determined by pre-pandemic levels of H1N1pdm antibody measured by HI.ConclusionsOur results claim for new studies to better identify the biological mechanisms, which might have determined the observed pattern of susceptibility with age. Moreover, our results highlight the need to obtain early estimates of differential susceptibility with age in any future pandemics to obtain more reliable real time estimates of critical epidemiological parameters.

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