DR. LICHTMAN: In this video, we will begin to talk about helper T cells,
where they come from and where they go to fight infection.
We just go back to the big picture
of the adaptive immune system.
Remember, there are B cells that make antibodies,
and there are T cells that come in two main types,
CD4+ T cells and CD8+ T cells.
We are going to focus on CD4+ T cells which are the cells that
become helper T cells.
Some helper T cells help to make antibodies,
and we have discussed this in some detail in previous videos.
Others fight infection independent of antibodies.
So let's start back in the lymph node
where helper T cells are first differentiated.
Remember that CD4+ T cells have antigen receptors that see
antigen which is a peptide and a class II MHC molecule.
That antigen is derived from microbes that enter the cell,
or microbial proteins that are degraded into peptides,
and the peptide is put on the class II HMC molecule.
This generates the antigen that the T cell sees,
and there is an important signal for the activation
of that naive T cell, and then of course
as we've discussed before, there is costimulation.
The result of these signals is that the CD4+ T cell expands
to many, many copies of the original cell.
But we've not discussed in that much detail before is that
in addition to clonal expansion, these CD4+ T cells
differentiate into T helper cells.
If this was the naive T cell, it makes lots of helper T cells.
So what is the difference between a helper T
cell and a naive T cell?
Well, the helper T cell has many functions that fight infection.
The naive T cell does not have those functions.
Now all this differentiation happens
within the secondary lymphoid organ like the lymph node.
As we described before, some T helper cells work with B cells
to form the germinal center reaction
to make good antibodies, but other T helper cells
will leave the lymph node.
If this is the lymph node we're talking about,
and for instance there's an infection--
for example in the hand here-- antigens from the infection
will be delivered to the lymph node
and activate the naive T cells to expand and differentiate.
And then the T helper cell will migrate out of the lymph node
and into the site of infection.
So if this picture is a magnification
of the site of infection, for example in the hand,
and we have microbes that have gotten past epithelial barrier,
some of them may die and release proteins,
this is the place where we want the T helper cells to go.
And these T helper cells will migrate through the blood
vessel into the tissue using many of the same mechanisms we
described for the migration of neutrophils and monocytes
when we described acute inflammation earlier.
So now we have a helper T cells in the tissue.
Within the tissue there are macrophages and dendritic cells
which can take up the microbes and the microbial proteins
and process them and put the peptides from the microbes
on class II MHC molecules, and these are the same antigens
that the T cell will recognise, that we described when
the naive T cell recognized the antigen earlier.
So now we have T helper cells seeing antigen and responding.
So how do they respond?
Well, the main thing that the T helper cell does in response
to the antigen is to secrete molecules called cytokines.
And the cytokines work on other cells, such as macrophages
or dendritic cells or neutrophils,
and these cells actually do the killing of the microbes.
So the helper cell is helping these cells.
It turns out that not all T helper cells are the same.
There can be a T helper cell, pictured here,
that makes a particular type of cytokine which
is really good at killing certain types of microbes that
tend to get into cells and live there without the help of the T
helper cell.
Another type of T helper cell may
make a different set of cytokines,
and that may be particularly good at fighting other types
of microbes pictured here.
For example, a worm, such as intestinal parasites.
And yet another type of T helper cell may make other cytokines,
and they may be particularly good at alarming neutrophils
to kill extracellular microbes.
So in summary, some T helper cells
that are generated in lymph nodes leave the nodes
and go to sites of infection.
At the sites of infection these T helper cells
get antigen exposure, they are activated
by antigens from the microbes, and they secrete cytokines.
The cytokines that are made by the T helper cells
work on other cells to actually do the killing of the microbes.
And it turns out that not all T helper cells are the same.
There are some T helper cells that
secrete some cytokines that are good for one type of infection
and other T helper cells, for instance,
that will secrete other cytokines that
will kill other microbes.
So I'll leave you with a few questions
that we can address in subsequent videos
that we've just touched upon here.
What are the different types of helper T cells
that we have just introduced?
Which cytokines do they secrete, and which types of infections
do they defend against?