March 9, 2005 | David F. Coppedge

Tissues Build Firebreaks to Avoid Disease

An article in the March 3 issue of Nature1 explains how tissues communicate to fight off infection.  As reported before, cells display samples of the proteins they contain on their outer membranes, a process called presentation.  Killer T cells wander around, like cops, looking at the presentations.  When they recognize alien proteins (antigens), they respond by killing the cell (see 06/27/2003 entry, “Cell to Phagocyte: I’m Dying – Eat Me”).
    Now, Dutch scientists Neijssen et al.2 have found that cells in tissues can also pass these flags to neighboring cells through passageways between them called gap junctions.  The uninfected neighboring cells thus signal the cops that a firebreak needs to be constructed to avoid further damage.  Australian biologists William Heath and Francis Carbone explain:

As well as providing another possible mechanism for initiating immunity by dendritic cells, the gap-junction-mediated cross-presentation described by Neijssen et al. offers an interesting method of efficiently limiting the spread of replicating virus.  The authors show that not only will a cell expressing viral proteins be killed by T cells, but so will its closest neighbours – because they present viral peptides obtained through gap junctions.  Extending the destruction to adjacent cells may provide a ‘fire-break’ around an infection, ensuring that if low levels of virus have spread to surrounding cells, but have yet to produce sufficient protein to allow recognition, such cells will still be eliminated.   (Emphasis added in all quotes.)

  The width of the firebreak is controlled, they explain: “The rapid degradation of peptides within the cell’s cytosol means that the spread of peptides through gap junctions will be rather limited, probably allowing the targeting of adjacent cells but not those more than one cell distant from the infection.  Thus, the integrity of targeting should be maintained, with only limited bystander destruction.

1Heath and Carbone, “Coupling and cross-presentation, Nature 434, 27 – 28 (03 March 2005); doi:10.1038/434027a
2Neijssen et al., “Cross-presentation by intercellular peptide transfer through gap junctions,” Nature 434, 83 – 88 (03 March 2005); doi:10.1038/nature03290.

Neither article attempts to explain how such a clever protective technique could have evolved.

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Categories: Health

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