In order to initiate a immune response, for the
adaptive T-cells and the adaptive B-cells, you
need these organized structures that we’ve already
referred to - the secondary lymphoid tissues.
And looking now at a lymph node, with some lymphocytes sitting
in the lymph node, those lymphocytes need to become activated.
So they need to encounter antigen.
And one of the cells that is crucially
important in activating naïve T-cells,
T-cells that have not previously encountered
the antigen, is the dendritic cell.
So these dendritic cells will arise from
hematopoietic stem cells in the bone marrow.
And the precursors of these dendritic
cells will arrive in the tissues.
Having come from the bone marrow they will
arrive in the tissues from the blood circulation.
And they sit in the tissues throughout
the body and they just wait there.
They just sit there waiting
in case antigen comes along.
And if they encounter antigen using their Pattern Recognition
Receptors, they detect PAMPs associated with pathogens.
They can take up the antigens because
at this stage in their development,
whilst they’re sitting in the tissues, they are phagocytic.
And they’re in an antigen uptake mode.
Recognition of the antigen activates these dendritic
cells and changes their mode of operating.
First of all, it tells them to move out of
the tissues and go to the local lymph node.
And they do this.
So following antigen uptake, they migrate via
the afferent lymphatics and into the lymph node.
As they migrate through the afferent lymphatics, they lose the
ability to become phagocytic, or to phagocytose microorganisms.
But importantly, they upregulate
the expression of MHC molecules
and of co-stimulatory molecules, particularly the B7 molecules.
So they now switch from being in an antigen
uptake mode to an antigen presentation mode.
And they present antigen to the T-cells,
thereby activating the T-cells.
And those activated T-cells can
now leave the lymph node via the
efferent lymphatics and go and do their job throughout the body.
So the activation of naïve T-cells requires… there’s
an absolute requirement for dendritic cells.
So using their Pattern Recognition
Receptors, these dendritic cells
which are present in the tissues at that stage are phagocytic.
And ultimately following activation can
process the antigen and deliver it to
the T-cell, following their migration
through the afferent lymphatic vessels.
And as we’ve already heard, MHC molecules,
particularly MHC Class II become
highly increased in their level on
the surface of the dendritic cell.
And likewise the B7
co-stimulatory molecules - B7.1
which is CD80 and B7.2
which is CD86, also are greatly increased in concentration
to facilitate antigen presentation to the T-cells.
So these antigen presenting mode dendritic
cells are present in the lymphoid tissues.
They’re not phagocytic, they don’t need to be phagocytic
anymore because they’ve already taken up the antigen.
But they have the necessary molecules on their cell
surface for antigen presentation and T-cell activation.
Just like B-cells become clonally selected, so the T-cells
become clonally selected, because you have the same situation.
You have a genetic recombination mechanism for the
T-cell receptors, just like the genetic recombination
mechanism for the B-cell receptors can create
millions and millions of different T-cell receptors.
So for each individual specificity, you don’t
have enough T-cells to get rid of the infection.
You maybe only have a few thousand.
You need to expand them up in number,
exactly like we saw for the B-cells.
So here we have a dendritic cell, it’s taken up antigen,
it’s processed it, it’s presenting it to the T-cell.
And this particular T-cell in the middle with the black T-cell
receptor is recognizing this particular peptide MHC combination.
So this T-cell will become clonally
selected, proliferation will be induced.
It will expand up in number so that
ultimately we have enough of those particular
T-cells to deal with the infection
that’s present at that time in the body.
As well as proliferation, just like we saw for the
B-cells, the T-cells also undergo differentiation.
So a naïve T-cell becoming activated by MHC
peptide, seen here sitting on the end of a
dendritic cell process, it becomes ac-- the
T-cell becomes activated, it proliferates,
expands up in number and then it will
differentiate not only into the cells that are
needed at that point in time, which we’re
going to refer to as effector T-cells.
So this might be a helper T-cell secreting cytokines, it might
be a cytotoxic T-cell that’s going to kill an infected cell.
But as well as most of those cells becoming effector
T-cells, some of them will become memory cells so that
we can generate a superior secondary immune response
upon a subsequent encounter with the same antigen.