This is the tale of murder, suicide, evolution, and resurrection, taking place in four parts, and all in the name of antigen cross-priming. We invite you to explore the dark mysteries lurking within each of us as you are guided through circuitous cellular pathways in a merciless fight for survival... with viral immunity being the grand finale?!
"In the latter model system, the use of transgenic mice expressing inhibitors of apoptosis in beta cells and the in vivo injection of biochemical modulators of death pathways have confirmed the critical role for cell death in both antigen transfer and T cell activation (Hugues et al., 2002; Turley et al., 2003; Giodini and Albert, 2010; Locher et al., 2010; Flinsenberg et al., 2011). Over the last decade, there has been an explosion of information regarding cell stress and cell death. "
[Show abstract][Hide abstract] ABSTRACT: Phagocytosis of dying cells constitutes an important mechanism of antigen capture for the cross-priming of CD8(+) T cells. This process has been shown to be critical for achieving tumor and viral immunity. While most studies have focused on the mechanisms inherent in the dendritic cell that account for exogenous antigen accessing MHC I, several recent reports have highlighted the important contribution made by the antigen donor cell. Specifically, the cell stress and cell death pathways that precede antigen transfer are now known to impact cross-presentation and cross-priming. Herein, we review the current literature regarding a role for macroautophagy within the antigen donor cell. Further examination of this point of immune regulation is warranted and may contribute to a better understanding of how to optimize immunotherapy for treatment of cancer and chronic infectious disease.
Frontiers in Immunology 03/2012; 3:61. DOI:10.3389/fimmu.2012.00061
"Notably, the initial studies employed an IVA infection model, after the transfer of matrix 1 (M1) from infected donor cells to uninfected human cDCs competent in presenting peptide epitopes derived from M1 on major histocompatibility class I (MHC I) molecules (Albert et al., 1998b; Albert et al., 1998a). More recently, it was suggested that autophagic processes within the dying IVA-infected cells are critical for achieving efficient antigen transfer and crosspriming (Giodini and Albert, 2010; Uhl et al., 2009). Intriguingly, M2-mediated inhibition may be central to these biologic pathways as inferred from the seminal observation that chloroquine, "
[Show abstract][Hide abstract] ABSTRACT: Manipulation of cell death pathways has been identified as a common feature of host-microbe interactions. We examine two examples: influenza A as a representative acute infection and cytomegalovirus as an example of chronic infection. From the perspective of viral entry, replication, and transmission, we identify points of interconnection with the host response to infection, namely the induction of host cell death, inflammation, and immunity. Following from this analysis, we argue that the evolution and fine-tuned regulation of death-associated genes may result from constant microbial pressure--past and present--that helped to support and coordinate cell death programs within the host. Interestingly, the delay in host cell death allows time for the virus to replicate while perturbations in cell death allow the host cell to initiate an immune response. This may represent a genetically encoded trade-off ensuring survival of both host and virus, or it may be a part of the complex agenda of infectious microbes.
[Show abstract][Hide abstract] ABSTRACT: Personal communications services (PCS) should support a number of
users that is several times larger than that of cellular systems. Using
the fact that many call patterns in PCS have the locality between the
callers and callees, the proposed mobility management strategy is able
to track the user locations efficiently in a hierarchically distributed
fashion. In the proposed structure, the larger number of nodes per
parent node shows better results. The virtually hierarchical link is
used to support the call locality, which is useful especially in the
long-distance roaming. The locality consideration effectively reduces
the query traffic compared with non-locality consideration
Global Telecommunications Conference, 1997. GLOBECOM '97., IEEE; 12/1997
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