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Saturday, May 06, 2006

Antigen Presenting Cells Fc and stuff

And now for something completely different.

I am interested in rational vaccine design. Therefore I am interested in the way in which antigens are dealt with by the immune system. I should warn that I am an economist and therefore don't know what I am talking about. OK my understanding is that what happens in an immune response is first the foreign entity (say a virus) sticks to an antigen presenting cell. It is brought into the cell via the normal process of pinocytosis (in English little bits going into cells) directed to a lysosome then to what is called the proteosome which was described after I dropped out of bio grad school.

Finally small bits of protein from the virus are presented on the surface of the antigen presenting cell either in the cleft of a protein called HLA class II antigen or tucked into another protein called HLA class I antigen. HLA class II is found on antigen presenting cells and antibody producing cells (called B Lymphocytes). HLA class I is found on all cells but red blood cells.

A bit of protein in HLA class II is presented to helper T cells where it is bound by a variable T cell receptor which present it to B cells which produce antibodies which stick to it. Most of us don't produce antibodies which stick to our own cells as the helper T cells with the appropriate T cell receptor have been told to die via a process which no one has managed to explain to me.

A bit of protein in HLA class I is presented to killer T-cells whith the appropriate recepter which are then "activated" and kill any cell with the bit of protein in HLA class I. Presumably the deceased cell had the virus in it.

Anyway it is key to get into an antigen presenting cell. Antigen presenting cells include macrophages which look like amoebas and wander around engulfing and destroying foreign entities when they are not presenting antigens. However most antigen presenting cells are dendritic cells (means they have tentacles) which are found in lymph nodes. They don't wander around they wait for foreign stuff to come to them.

I don't know about dendritic cells, but I know that macrophages have Fc receptors which bind to antibodies. Objects covered with antibodies stick to the Fc receptors of macrophages which then phagocytize (eat into the cell) them. The aim in this case is to kill the foreign entity if it is alive. Phagocytized stuff is directed to Peroxisomes which are bags full of peroxide and the graveyard of many bacteria and, especially, malaria.

Fc is the part of an antibody which is the same in all antibodies. It is important because it binds to Fc receptors, binds to something which prevents antibodies from being digested in the liver and binds complement (which I do not pretend to know what it is but it is important).

It is a fact that, if something is covered with antibodies, the immune system does not make a new reaction to it. antibodies are about the best inhibitor of a new immune response including activating killer T cells and making new types of antibodies.

I have a guess that the issue is that antibodies with Fc receptors direct the foreign entity into the peroxisome and not into the antigen presentation pathway (lysosome and proteasome).

If so it might be possible to make an antigen to which odd antibodies are made by first making normal boring antibodies, then cutting off the Fc part (this is easy) and putting the antigen back in for another go at the antigen presenting business etc etc.

Also I reall think that it should make sense to direct antigens towards the antigen presenting cell with bifunctional Fc less antibodies one half of which sticks to the antigen and one half of which sticks to an antigen presenting cell specific antigen.

That is all.

econgeek has left a new comment on your post "5/06/2006 10:14:00 PM":

You went to bio grad school?!?!? And more importantly, if you did, why on earth did you drop out?

Yes I did and got a masters degree which I have kept off my CV because getting a masters and not a PhD means you are a dropout. Actually doing research in biology requires a huge amount of boring work and the key necessary traits are attention to detail and self discipline. Econgeek is actually a regular reader of this blog and will have noticed my complete lack of interest in spellling, grammer and punctuation these are not important in biology, but negadiscipline makes me suited for almost no jobs at all.

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