- Selectins play a critical role in white blood cell migration to sites of infection,
this is one main thing they do.
- So what we’re looking at in this diagram is a blood vessel, so this endothelial
cell layer on one side, this is a type of epithelium – in this case it is called an
endothelial cell layer since it lines a blood vessel but it is an epithelium just like
other epithelium we discussed about. Here is the white blood cell, normally it
would be flowing through the blood stream so going through all of our blood
vessels, surveying the system looking for infections. When an infection happens
in the tissue outside of this blood vessel, it starts sending signals to the blood
vessels saying there is a problem, that there is a bacterial infection or something
like that. This infection leads to these epithelial cells changing their properties.
They express different things on their cell surface and one key thing they express
is the selectin, the cell adhesion molecule. These specific cells here begin to
express selectin so that they can stick to that white blood cell. Instead of this
white blood cell flowing by in the blood stream, it can now be captured by the
endothelium so that it can start to attack this infection.
- The first thing that happens in this selectin dependent step, here it is illustrated
with this flash of yellow and so, when this cell starts to express selectin, the white
blood cell travelling through the bloodstream will all of a sudden get attached to
one side with these selectins and that will start that cell to actually start to roll as it
grabs hold to one side and the rest of it starts going so it rolls over on itself. This
will make more selectin contacts and more selectin contacts and that starts to lead
to further signalling which induces a second step where there are much stronger
adhesion and this is integrin dependent and we’ll talk about integrins next week,
how they function so we will revisit this slide later. This leads to tight adhesion to
the endothelial layer and the white blood cell will pass through the epithelium to
fight the infection. The selectins play a key role in the initial binding of white
blood cells to target these white blood cells to sites of infection.
! Ig-like extracellular domains
! Calcium-independent, homophilic and heterophilic receptor interactions
- Here is another main class of anchoring junctions. These junctions here, they
involve this other type of receptor & these receptors are called immunoglobulin
superfamily & it is called this b/c the receptors contain multiple Ig-like
extracellular domains. These Ig-like domains, these are the same domains that are
found in antibodies so that is why it is called Ig immunoglobulin-like, same as in
antibodies. So it is this little domain in red, the one that is connected by this
disulfide bond that is one of these Ig-like domains so in this receptor you have 5
of these Ig-like domains but this is all one polypeptide chain running from the
extracellular, crossing the membrane and having the C terminus of this protein in
- These Ig-like domains can mediate homophilic or heterophilic receptor
interactions – they can bind like with like or different receptors and the key
difference here with the cadherins is that these guys are calcium independent.
They bind independent of calcium. But like the other adhesion complex, these
also link to the cytoskeleton and they function in many tissues.
- He wants to point out in the handout that there is a typo mentioning the NCAM
but we see the NCAM receptor is the neural cell adhesion molecule so it is a
receptor that works in neural cells to mediate cell-cell adhesion. The other one is
ICAM and so note down that this is intercellular cell adhesion molecule – this is a
molecule that works in the immune system to mediate cell-cell adhesion. These
are a couple of examples of two different receptors acting to mediate cell adhesion
between different types of cells in the body.
! Intermediate filaments
- The last type of anchoring junction he would like to discuss is desmosomes.
- Here we have a desmosome in the slide, and these structures are based on
adhesion between cadherin-like receptors. We are looking at the full structure of
this cell adhesion complex, one plasma membrane on the left and another plasma
membrane on the other side. The light green structures are the individual cell
adhesion molecules and you can see how they’re all clustered together to make a
typical cell adhesion complex. The cytoplasmic tails interact with adapter proteins
and these adaptor proteins link to intermediate filaments so these are different
than the adherens junctions talked about last day linked to actin. These ones link
to intermediate filaments, a different cytoskeletal system.
! Intermediate filaments
! Strengthening tissues
! Tensile forces eg. Skin
- We heard about the fact that intermediate filaments are important to give
strength to tissues so the desmosomes play a key role in this – they act together
with the intermediate filaments to provide strength across the tissue and not
surprisingly, they’re found in tissues exposed to lots of physical stress, lots of
tensile forces like the skin. These desmosomes are found throughout your skin
together with intermediate filaments and support the structure of our skin.
- That is this picture that we looked at a couple times now. We now know the
components of the picture.
- There is an individual cell in the middle, the green is intermediate filaments and
the blue are desmosomes. We have intermediate filaments that link up to a
desmosome and they come in at that desmosome from both sides. The
desmosomes connect up the intermediate filament of one cell to the intermediate
filament system of another cell creating a strong network of protein running
through the whole tissue. This is what is happening in our skin to give it strength.
- Why is this type of epithelial structure important? Why is it important to form
sheets of cells? There are sheets of cells, one cell is rectangular, they’re all
connected together in this sheet. Why is this important for the structure of the
adult body plan?
- The key thing is epithelia forms boundaries between body compartments.
- It is critical, for example here in the lumen of our gut, there is a high level of
acid and we don’t want the acid to escape from the gut and to run into other
tissues, digesting away the connective tissue, muscle cells beneath.
- That is one key aspect of keeping things separate and not only do you want to
keep things separate but the body must have selectivity to these barriers so they’re
selective barriers – some things are allowed to cross, other things are blocked.
- For example we just saw that if the epithelial layer down there was the lining of
the blood vessel, we just saw how an immune cell, if the immune cell was a white
blood cell travelling through this blood vessel, if there is a site of infection in the
yellow part, we saw how it could attach to the epithelial layer and go across it so
it is a selective barrier that can allow some things to cross.
- Also in the gut, you have food being digested so there are nutrients and energy
supplied from the gut and that has to pass out of the gut to all of the other tissues
in the body so we can make use of those nutrients and the energy supply. They are
boundaries but they’re selective boundaries.