Immune reaction to “new” protein

Immune reaction to “new” protein

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I read in Bruce Alberts Molecular Biology of the cell :

Normal mice,for example, cannot make an immune response against one of their own protein components of the complement system called C5. Mutant mice, however, lack the gene encoding C5(but are otherwise genetically identical to the normal mice) can make a strong immune response to this blood protein when immunized with it. Natural immunological tolerance for a particular self molecule persists only for as long the molecule remains present in the body. If a self molecule such as C5 is removed, an animal gains the ability to respond to it after a few weeks or months. Thus, the immune system is genetically capable of responding to self molecules but learns not to do so.

So, why does an immune reaction not happen when a new protein is introduced to patients lacking it ? For example if you give clotting factor to hemophilic patient.

They actually can produce antibodies against the clotting factor (as @Xylo pointed out, many patients do produce the clotting factor that's being replaced, just in insufficient quantity, which lowers a lot the risk of an immune response). The antibodies against the clotting factor are called inhibitors. See here for more info.

You are absolutely right in that there will be immune reaction against proteins that are not naturally present in the body.

However, hemophilia is not caused by complete lack of protein. It is due to loss of function of the clotting factors due to mutations. The proteins are still present, but they do not have the ability to bind and/or activation of their catalytic function. So, there will be no immune activity against exogenous clotting factors given to hemophiliac patients.

This is a concept of the immune system called "Immune tolerance". Basically it makes sure, that you cannot make antibodies against yourself (which would obviously be bad). New antibodies are "tested" against the body and if there is an autoreactivity, the corresponding B-cells go into apoptosis. If this self-protection does not work, this leads to autoimmune diseases like SLE. The Wikipedia article about it is quite nice for the beginning and also has a lot of references for further reading.