Ok, so in class we are talking about how mouse derived antibodies cannot be ther

Question

Ok, so in class we are talking about how mouse derived antibodies cannot be theraputically used in humans because they are foreign. Instead, we can use recombinant DNA to produce an antibody that contains the V region from a mouse and the C region from a human. He says that this hybrid antibody is still immunogenic because of the mouse V region, but not as much as an antibody that is entirely mouse derived.

My question is, if our immune systems are capable of mounting a response to variable regions on Ab, how do we not produce immune responses to our own variable regions. Are all our antibodies tolerated against all the endless combinations of our other antibodies...That seems unlikely? How does this work?

Explanation / Answer

I'm sure you know all about antigens and antibodies because you are clearly learning about them, but I'll give a little summary to try and make sense of my [novel of a] response. Antibodies are an immune response that specifically recognizes and bind to foreign particles to have them removed from the body. Each antibody is formed of light chains and dark chains (light and dark just refer to staining), and each antibody has constant regions and variable regions. The variable region is what recognizes and attaches antigens, and it's specific. The constant regions are constant in each antibody for a variable class, IgG, IgA, IgM, IgD, and IgE, where each class performs a slightly different immunological function in the body. Once the antibody binds, it can produce a response in several ways. First, we need to get the right picture in our minds: antibodies are very, very small. In most cases, when compared to the antigen they are trying to attack, they are tiny. It isn’t like this antibody can come in and just destroy its target. Some antibodies can inactivate the antigen through binding, for example it can cause a slight conformational change in a viral coat protein that will make it harder for the virus to attach to a cell. Binding of the antibody can also send a chemical signal which will induce phagocytosis by a larger native cell, such as a macrophage, or it can activate a complement system of an infected cell, causing the cell to autolyse. However, to perform both of these second tasks, the antibody has to be able to present a signal to the environment to flag down a macrophage or to lyse the cell. This “flagging” system will vary between mouse and humans. In fact, the signalling system of a mouse antibody will most likely flag a response of the native antibodies, trying to figure out what this foreign entity is sending out these markers and flags. The constant region is the part that signals, so having that vector as the human form will “protect” that antibody, in a sense, from being attacked by the immune system. That being said, your body is still going to recognize if there is foreign DNA in your system on that variable region – it’s the beauty of our immune system. That is the bit about the mouse and that is what you need to know about that, because you are actually right about the second part – our bodies make a TON of different antibodies with a TON of variable regions. Our immune system contains specialized cells called B lymphocytes. Each B cell makes only one type of antibody protein, but there are (pardon my abuse of this word) TONS of B cells in the body. This means we have an immense array of different antigens. And if you think that is unlikely and wasteful and maybe not the best method, you’re really not going to like HOW we make all these different antigens, because it’s not like we have space in our genome to code all these antigenic regions. Immature B cells are formed by precursor stem cells that have undergone a series of recombination events of small segments during development. So basically, the reason we have all these different variable regions is similar to watching a Casino dealer shuffle cards – a bunch of regions are randomly thrown together. These immature B cells then go around displaying their antibody until an antigen is found that matches, which sets of a chain reaction that stimulates that B cell to proliferate and divide into two new types of cells: plasma cells and memory cells. Plasma cells are used for the reaction response of this infection, and then memory cells dormant (and they can remain dormant for years) until a new infection occurs that triggers the same antibody. These memory cells can produce antibodies so fast, they usually clear up the infection before any symptoms even appear. That was a very long explanation to a very short end point: The reason that the mouse DNA triggers a response is just for that reason – it is mouse DNA. The body recognizes that it isn’t some variable human DNA sequence (that is a whole separate lesson on its own, how different types of DNA are recognized, and it has to do with bound proteins and DNA-protein complexes... blah blah blah) but that it is foreign DNA. The body doesn’t mind variable DNA, it doesn’t like the foreign type. Moral of the story: Evolution doesn’t mean things are done in the most efficient way. It just means the job GETS done, even if it’s the ugliest, most round-about way. Sorry that was a novel, BTW, but I hope it helps!

Related Questions

Navigate

• Browse (All)
• Browse O
• Subjects

Integrity-first tutoring: explanations and feedback only — we do not complete graded work. Learn more.