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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.

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up vote 3 down vote accepted

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.

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Thanks ! In the link you provide, it is written that the reason for this is uncertain. Do you think the reason could be the one I pointed out in the post ? – biogirl Dec 16 '13 at 17:25
Yes, and my understanding is that the uncertainty resides in the fact that even some patients which do produce endogenous clotting factor sometimes react, while you'd expect they shouldn't. – Roberto Dec 16 '13 at 17:26
Does the endogenous clotting factor reaction classify as autoimmune ? – biogirl Dec 16 '13 at 17:29
Sometimes the antibodies are actually the origin of the clotting problem and in that case yes, absolutely. Now when the patient is naturally lacking any production of that factor and the antibodies appear due to therapy, then I guess so but I'm not sure, sorry. – Roberto Dec 16 '13 at 18:07
No worries! Thanks a lot ! – biogirl Dec 16 '13 at 18:08

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.

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Thanks ! I am not able to recollect any examples but isn't there any disease where a protein is totally not made and then we artificially give that protein ? – biogirl Dec 16 '13 at 17:16
When it comes to genetic disorders, you have to remember humans have diploid chromosomes. Most eukaryotes are diploid. So, if there is deletion of a gene on one chromosome its allele would still be present and its gene product will be made in the tissues/cells that they are normally expressed. – Xylo Dec 16 '13 at 17:24
ok! SO it is extremely rare that there will be disorder such that no protein is expressed but I think there can be at least one ! – biogirl Dec 16 '13 at 17:29
I cannot recall any specific disease where both copies are deleted. But, it is possible. <br /> An example of the situation you are describing would be blood determinant antigens, O, A and B. When people with O-type are transfused with A-, B- or AB-donor blood, there will be immune reaction against it. <br /> So, to summarize, if you transfuse with protein that was not present will definitely generate an immune response. – Xylo Dec 16 '13 at 17:35
It is not in the spirit of the site to ask someone to accept/upvote your question/answer. – user4058 Dec 16 '13 at 17:40

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.

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