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Title:   Author  item
                                            BUTLER, JOHN - University Of Iowaitem
                                            SUN, X-Z - University Of Iowaitem
                                            WERTZ, N - University Of Iowaitem
                                            Baker, Amyitem
                                            ZANELLA, ERALDO - Universidad De Passo Fundoitem
                                            Lager, Kelly
  Submitted to: Immunology
                                    Publication Type: Peer Reviewed Journal
                                    Publication Acceptance Date: 10/2/2012
                                    Publication  Date: 2/1/2013
                                    Citation: Butler, J.E., Sun, X., Wertz, N., Vincent, A.L., Zanella, E.L., Lager, K.M. 2013. Antibody repertoire development in fetal and neonatal piglets. XVI. Influenza stimulates adaptive immunity, class switch and diversification of the IgG repertoire encoded by downstream C-gamma genes. Immunology. 138(2):134-144.Interpretive Summary: The immune system helps protect animals from disease. It can be divided into two compartments, the humoral and cellular immune system that work together against infectious agents. Humoral immunity involves the production of antibodies by B cells, a type of cell that circulates in the blood. Cellular immunity involves T cells, another type of blood cell that can "attack" infectious agents using several mechanisms. Viruses and bacteria are constantly mutating trying to improve their chances to infect animals. Vaccines can be used to enhance the immune system to minimize or prevent infections. To better understand how a vaccine might be improved, it is necessary to understand more about the immune response. This paper describes studies investigating the development of the humoral immune response against swine influenza virus using germ-free pigs as the animal model. This response involves the development of a specific class of antibodies suggesting if this response could be enhanced, then the overall immune response against influenza virus might be enhanced. This knowledge may be applied towards developing future vaccines that stimulate a specific class of antibodies to better fight a disease like swine flu.
                                Technical Abstract: Infection of germfree isolator piglets with swine influenza (S-FLU) that generates ds-RNA during replication causes elevation of Igs in serum and bronchial alveolar lavage (BAL), a very weak response to TNP conjugates but an immune response to S-FLU. The increased Igs levels result mainly from the polyclonal activation of B cells during the infection, but model antigen exposure may contribute. The 10-fold increase in local and serum IgG accompanies a 10-fold decrease in the transcription of IgG3 in the tracheal-bronchial lymph nodes (TBLN) and in the ileal Peyers patches (IPP). Infection results in class switch recombination (CSR) to downstream C-gamma genes which diversify their repertoire; both features are diagnostic of adaptive immunity. Meanwhile the repertoires of IgM and IgG3 remain undiversified suggesting they encode innate, natural antibodies. While IgG3 may play an initial protective role, antibodies encoded by downstream C-gamma genes with diversified repertoires are predicted to be most important in long-term protection to S-FLU.


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