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Aging blurs what counts as self
Two books of sounds
In World War II, submarines carried two sets of books. One held the engine sound profile of every US submarine, so a crew that heard a General Motors engine cycle held its fire. The other held the sounds of known German diesel engines, and hearing one of those meant firing at once. A famous immunologist in the 1970s used this as the picture of self versus non-self, the sorting problem the immune system faces.
The self book grows
Over the years the self book keeps growing. Cells collect mutations, so the body fills with cells that differ from their neighbors, and the books start to hold every possible permutation of every biomolecule the body could make. A virus then has less that is unique about it, and the T cell response against its proteins has more noise to cut through.
Why cancer slips by
That is one reason cancer is more common later in life. Cells have accumulated mutations that could turn cancerous, and the immune system has watched those changes pile up for years, to the point where the weird no longer looks that weird. A cancer cell differs little from the cell next to it that is happily making skin.
How does the immune system see inside cells?
Nearly every cell in the body carries molecules called MHC class I on its surface. These molecules hold small fragments of proteins being made inside the cell and display them on the outside. A T cell passing by reads those fragments, which works like checking the cell's inventory. When the fragments come from a virus or a mutated protein, the T cell can kill the cell.
Why does cancer become more common with age?
In the 1950s, Peter Armitage and Richard Doll noticed that cancer rates climb steeply with age, in a pattern that fit a multistep process. Their model proposed that a cell needs several separate changes before it becomes cancerous, and that those changes take time to accumulate. Later sequencing of tumors supported the idea that most cancers carry multiple driver mutations. Each added year gives more time for those changes to pile up in the same cell.
How else does the immune system change with age?
The thymus shrinks over the years, so fewer fresh T cells that have never met an invader are made. Meanwhile memory T cells pile up, and in many older adults a large share of them target a single common virus, cytomegalovirus. Vaccines generally trigger weaker antibody responses in older adults than in younger ones. Researchers call this gradual decline immunosenescence.
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