by NP, M1 and PB1, PB2) [78-81]. adaptive immune mechanisms mediated by influenza specific B- and T-cells involved in the anti-influenza immune defense together with the contribution of innate immunity. We discuss the mechanisms of neutralization SGL5213 of influenza contamination mediated by antibodies, the role of CTL in viral removal and new approaches to develop epitope based vaccine inducing cross-protective influenza virus-specific immune response. 1. Introduction Influenza remains a serious respiratory disease in spite of the availability of antivirals and inactivated trivalent vaccines, which are effective for most recipients. Influenza viruses are RNA viruses with strongly immunogenic surface proteins, especially the hemagglutinin. Error-prone RNA-dependent RNA polymerase and segmented genome enable influenza viruses to undergo minor (antigenic drift) as well as major (antigenic shift) antigenic changes, which permit the computer virus to Rabbit Polyclonal to GNA14 evade adaptive immune response in a variety of mammalian and avian species, including humans. The unpredictable variability of influenza A viruses, which cause yearly epidemics in human population, is the main reason why no effective prevention against influenza SGL5213 contamination exists up to date. Currently available vaccines induce antibodies against seasonal and closely related antigenic viral strains, but do not protect against antibody-escape variants of seasonal or novel influenza A viruses. Therefore, there is a call for development of a vaccine, which would be protective against computer virus strains of different HA subtypes and would not need to be updated every year. New approach to prepare a universal vaccine lies in the selection of conserved epitopes or proteins of influenza A computer virus, which induce cross-protective immune response, particularly M2, HA2, M1, NP [1-3]. 2. Induction of adaptive immunity by influenza contamination Influenza contamination induces specific humoral immunity represented by systemic and local antibody response, as well as cellular immunity, represented by specific T-cell response (Physique ?(Figure1).1). Both of them are important in the host defense against influenza contamination, because of their close cooperation mediated by numerous immune mechanisms. Dendritic cells and macrophages (antigen presenting cells, APCs) play an important role in initiating and driving of adaptive immune response [4]. Exogenous SGL5213 viral antigens, including inactive viral particles, intact viruses or infected cells, are taken up by APCs through endocytosis or phagocytosis. Their further processing results in generation of peptides that are offered via MHC I or MHC II molecules to CD8+ precursor T-cell and CD4+ helper T-cell precursors (Th0), respectively. Th0 cells are subdivided to Th1- and Th2-type helper cells, based on the cytokine profiles they produce. Following influenza contamination, APCs secrete IL-12 that contributes to the differentiation of Th0 into Th1 cells, which secrete IFN- and help to produce IgG2a antibodies [5,6]. Th1 cells also produce IL-2, required for the proliferation of the virus-specific CD8+ CTLs. In contrast, when IL-10 is present early in the immune response, Th0 cells differentiate to Th2 cells, which secrete IL-4, IL-5, IL-6 and help preferentially drive IgG1, IgA and IgE Ab production by antibody-secreting plasma cells (ASCs) [6-9]. CD8+ precursor T-cells, which maturate into CTLs (cytotoxic T lymphocytes), release antiviral cytokines (IFN-) upon acknowledgement of short viral peptides offered by MHC I molecules on virus-infected epithelial cells, and eliminate the computer virus infected cells by exocytosis of cytolytic granules. The granules contain cytolytic protein perforin and granzymes. Perforin is usually a protein that creates pores in membranes of infected cells. Granzymes are users of serine protease family. In the presence of perforin, granzymes enter into the cytoplasm of infected cells and initiate proteolysis, which triggers destruction of the target cell [10,11]. CTLs could mediate killing of infected cells SGL5213 also by perforin-independent mechanisms of cytotoxicity. This involves binding of Fas receptor in the infected target cell membranes with the Fas ligand (FasL) expressed on activated CTLs. Conversation of FasL with corresponding Fas receptor prospects to the activation.
