Ben - Now also in the news this week researchers at the Howard Hughes medical institute at Caltech have followed an antibody as it passes through the wall of the stomach. This must happen for mother to pass on immunity to a baby through breast milk. In order to see what happened they attached nano sized particles of gold to antibodies that they then fed to rats. Professor Pamela Bjorkman was leading the work and joins us now. Hi, Pamela.
Pamela - Hello
Ben - So Pamela, how did you actually do this? How did you see these antibodies passing through the stomach wall?
Pamela - Well, first we used a technique called electron tomography. Normally with electron microscopy, you take images of cells and you see their organelles. You can normally achieve nanometre resolution. So you can see membranes and other things like that. By attaching the nanogold particle to the antibody we could trace it as it was taken up by the intestinal cells. We could watch which parts of the inside of the cell it progressed as it was going across the cell.
Ben - Now, a lot of the time with these sorts of experiment people use something like a fluorescent tag which they attach to whichever chemical they are trying to follow. Would this have been possible or is it vital that you used this nano scale gold?
Pamela - A fluorescent tag wouldnít be visible in an electron microscope because what you need to see there is very electron dense particles. So the gold tags that we were using were actually 55 or 60 gold atoms that were attached. That is electron dense enough that with a little bit of an enhancement procedure we could see those. Every time we had a transport event we could visualise that by one of these gold tags. We were looking at single receptor bound to an antibody in each case. It was visible by the gold tag.
Ben - So once the antibody binds to the receptor how does it get through the cell? How does it push through?
Pamela - Well, it comes in through what is called receptor mediated endocytosis. It binds to its receptor which is on the side of the intestine it faces when milk comes into the gut. It binds there. It then goes inside to the cell, into these membranous compartments that are very strange shapes but theyíre tubes or theyíre like big spherical balls. It goes inside those and those are acidic and this receptor binds very tightly to the antibody at an acidic pH. These vesicles wander around inside the cell and then when they reach the side of the cell that faces the blood stream, which is where they eventually want to dump their cargo. These little tubules fuse with that membrane. Then theyíre exposed to the pH of blood which is slightly basic and at that pH the antibody rapidly falls off, enters the newborn bloodstream and the result is that it acquires its motherís antibodies.
Ben - So itís the difference in pH between inside your gut and inside your bloodstream that actually makes this a one-way process?
Pamela - Exactly.
Ben - So why is this so important, why do we need to transfer antibodies from breast milk to blood?
Pamela - It turns out that human babies donít develop fully functional immune systems until later. Itís very helpful to them to have some of their motherís antibodies. It is like a path of immunisation. The mother vaccinates them with antibodies against whatever pathogens she encountered in her environment. Thatís directly relevant to what the baby will experience. It has been immunised by its mother.
Ben - Could this be the same mechanism through which things like HIV are transferred from mother to baby?
Pamela - HIV is transferred through breast milk but actually there is a bit of a technicality. Most of the types of antibodies that are in breast milk are not the types that are transferred by the receptor we were studying, in human breast milk anyway. We were studying the transfer of IgG antibodies. Most of the antibodies that are in human breast milk are IgA. Rodents transfer IgG through breast milk, humans transfer IgG before birth: mostly across the placenta. Much of the antibodies that humans acquire is before they are even born. Itís by a transfer across the placenta. Then human foetuses swallow amniotic fluid and it is possible that they transfer maternal IgG to their bloodstream through the swallowing of this amniotic fluid that contains the motherís antibodies. I donít think that human babies actually acquire HIV through this mechanism.
Ben - Fantastic. Thank you ever so much Pamela. That was Professor Pamela Bjorkman from Caltech explaining how you can use gold or tiny particles of gold to shine a light on biological processes.