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My name is Paul Fairchild and I'm based at the Sir William Dunn School of
Pathology at Oxford University, where I'm also a fellow of Trinity College.
What I want to do is to give you a broad overview in this lecture of
a particular cell type which is absolutely crucial to the immune system,
and that is, of course, the dendritic cell.
The reason that dendritic cells are so critical
to the immune system is that all immune responses,
whether protective or pathogenic in their own right,
are initiated by the presentation of antigen to naive T-cells by dendritic cells.
But dendritic cells are also a cell type which is very close to my own heart
because I first encountered them as a PhD student back in the late 1980s,
and I've been studying their properties, on and off, pretty much ever since.
I've spent many happy hours in the presence of dendritic cells.
Let me begin by giving you a little historical perspective.
Dendritic cells were first discovered back in the early 1970s by Ralph Steinman and
Zanvil Cohn as a unique population of
leucocytes in the spleens and the lymph nodes of mice.
It was that observation which earned
Ralph Steinman the Nobel Prize for Medicine or Physiology back in 2011,
which was something of a bitter-sweet award.
He sadly died just two days before the award was announced,
and so never knew that he'd been awarded the Nobel Prize.
Nevertheless, his name will always be associated with
dendritic cells, and his contribution to immunology will always be acknowledged.
He was the first to call these cells
dendritic cells in recognition of their very complex morphology,
but also to reflect the fact that they can interdigitate among
naive T-cells in the secondary lymphoid tissues to form quite complex clusters of cells,
and you can see some of these in this photomicrograph.
Although he worked with Zanvil Cohn, particularly on macrophages,
it soon became clear that dendritic cells can be
distinguished from macrophages on a number of different bases.
First of all they constitutively express MHC class II molecules, but more importantly,
they have the unique capacity to stimulate antigen-naive T-cells
in an assay which has since become known as the 'mixed leukocyte reaction'.
Macrophages in that same assay fail completely to
stimulate naive T-cells, and fail to induce their proliferation.
Dendritic cells are unique when measured via the mixed leukocyte reaction.
Although dendritic cells were first discovered as
that population in the secondary lymphoid tissues of mice,
they were subsequently found to be distributed throughout
all interstitial tissues and peripheral organs of the body in an immature form,
where they serve as 'sentinels' of the immune system.
They have that capacity to sense the presence of
infectious microorganisms within the local vicinity.
Quite how these cells in peripheral tissues are related to the cells originally
identified by Ralph Steinman in
the secondary lymphoid tissues has only become clear in recent years,
but it's a journey of discovery that has helped us understand how
these cells help to bridge so effectively, innate and adaptive immunity.
The ability of dendritic cells to span these two arms of