Welcome to the cytokine lecture.
Cytokines are basically informational molecules,
and we're going to use that to signal from one cell to another.
One insight we've had from biology of late
is that signaling is critical to any biological function.
Bacteria do it to each other.
It's part of development.
It's part of any basic physiology.
And it's certainly central to managing the immune response.
Now, you might have noticed that at the beginning of this outline,
I put in a quote that's 100 years old, and it
refers to the distribution of nematodes throughout the environment.
They're not only ubiquitous, they're tailored to essentially parasitize off
of everything they can find.
And that is a challenge that we have faced since before we were even human.
So when we're looking at the immune system,
one of the things that we're going to be looking at in terms of signaling
is how you adapt your response to the particular pathogen challenges
that you face.
In the case of worms, we're going to use a somewhat different strategy
than we would use in the case of a flu infection.
And I mentioned that, I think, the first week of the first course.
We have an all-out war response against serious bacterial and flu infections,
because if we don't, they'll kill us.
On the other hand, we have a much more restrained response
that we do if it's certain kinds of chronic infections,
particularly certain kinds of worm parasites.
We use a more containment approach that is
less likely to damage our own tissues and to basically
claim too many of our resources.
So what we're going to look at, among other things in the cytokine lecture,
is how we decide how much of an effort to put
into fighting off a particular threat.
And to do that, the Th cells in particular
will gather in a lot of information from a variety of sources and then
will distribute that information in terms
of organizing how to fight the response.
One other thing that's come out of this is
that when you look at the Human Genome Project and you look at the genes
that you find in humans, I would refer to our genome
as administratively top heavy.
If I look at a bacterium, I will see that it
has lots of genes for enzymes that chew things up,
for proteins that make up its structure, and indeed, it
has some enzymes that are in there to control things-- or rather proteins.
OK, it has operon proteins.
It has transcription factors.
And it has that.
But they're not the majority of proteins.
If I look at the human genome, the majority of proteins
are things like transcription factors, signaling molecules,
the receptors for those signaling molecules,
and the genes for the enzyme sequences that
essentially pass that information on.
Now, you can get that information in a variety of ways.
One of the biggies is cell to cell contact.
If we looked at presentation of antigen to a Th cell,
we were looking at one cell contacting another.
If we look at the recognition of pathogens by, say, a macrophage,
that happens when the pathogen contacts its toll-like receptor.
And there are other examples of this.
And I think I put a few more in the outline.
In addition to that, there are specific signalling molecules
that are present on the surface of the cell.
And we call these things juxtacrine signals.
It's essentially, in most cases, a little protein that
will reach out and touch another protein receptor on another cell
and transfer a piece of information.
One of the nastier pieces of information you can get
is the signal that says basically, die sucker.
So in the next lecture, we're going to look at something called Fas ligand
on a cell that reaches out and touches a target cell that
maybe has gotten malignant, and says, I want
you to kill yourself right now by programmed cell death.
OK, juxtacrine connection.
You clearly don't want a signal like that running around your whole body.
Now, another type of signal-- and this is really more of the kinds of signals
we're going to look at in this lecture-- is a paracrine signal.
The immune system uses a lot of chemical signals
that go back and forth themselves, but they don't usually
travel a huge distance-- typically four-cell diameters at the most.
So these are local signals from one cell to another cell that
help to coordinate an immune response, maybe up-regulates some things
or down-regulate others or tell a cell to do a specific form of development.
OK, that's a paracrine factor.
This is distinct from what you might have studied in other courses
as hormones.
Hormones are secreted into the blood supply
and will travel throughout the whole body
and generally exert their effects-- or at least are capable of doing it--
a long way away from the secreting cell.
Paracrine factors are much more local.
So when we're looking at most of the things we're looking at now,
they're going to be in the general category of paracrine factors.
But of course, they don't have that name.
When you get into the immune system, the immune system
likes to put its names on everything.
And so most of the paracrine factors are referred
to generally as interleukins, which means
it goes from one white cell to another white cell.
And you remember the stuff we had with complement?
You remember the stuff we had with CDs?
It's that same awful thing all over again.
They are numbered IL-1 on up to-- I think there were 29 in the textbook.
There are probably 50 or 60 of them by now.
And again, the numbers tell the order in which it was discovered.
They don't tell you anything about it.
And I'm going to apologize for this in advance,
because here it is all over again.
I'm going to be using a lot of really confusing IL-whatevers
for the names of some of these factors.
And there's more.
OK, some of them have also names that were
named before they began numbering them.
Just like the complement proteins, there are some strange idiosyncratic names--
TNF for tumor necrosis factor.
Somebody found a signal that caused tumors to decay,
and later on, they realized that this was really
an immune signal that was a general inflammatory signal.
We've got interferons.
We've got a number of things that, we'll look at them
and I'll name them as we go along.
I will try to make these names something you can remember, but all I can do
is apologize in advance for immunologists' complete refusal
to make their naming system accessible to the average person.
This is just something we live with.
The other name that you're going to get is something called a chemokine.
OK, chemo means chemical, kine means motion.
This is going to be an interleukin, or paracrine factor, that's specifically
involved in making leukocytes, specifically neutrophils, sometimes
T cells, but some white cells go from one place to another.
So a chemokine is something that redirects an immune cell-- often
neutrophils and macrophages but also lymphocytes
as well-- to the site where it is needed.
Now the nice thing about that, when we look at them,
is we will see that they're all in the same general category, at least most
of them are.
It's a seven-span protein that again triggers a G protein.
That may sound bad, but you learn it for one of them,
you learn it for all of that.
And we'll see that when they're represented in the diagrams,
they're typically represented as something
that looks like a bicycle rack.
And it actually is-- you can see one, two, three, four, five-- oops, one,
two, three, four, five, six, seven places where this crosses the membrane.
It curves in around to form a site for things to bind.
And we will be looking at that specific one
a great deal when we look at the inflammatory response.
So again, get ready for a really nasty load on your memory.
I will try to make it clear, if not interesting.
And here we go.