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21. Immunological tolerance: Difference between revisions

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21. Immunological tolerance (view source)

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(Created page with "Tolerance is the act when the immune system does not act against a specific antigen. It happens all the time, because your immune system meets with antigens from your own body every second. However, some types of tolerance work by having the immune system never ''meet'' the antigen in the first place, as we will see. Unless you have a problem with your immune system, it should always tolerate self-antigens and never ever attack them. However, for some of us, that’s not...")
 
 
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The “passive” in passive tolerance means that either no cells will recognize the antigen that is tolerated, or the response against it is stopped just after the recognition. Passive tolerance is further divided into two parts: the central and the peripheral tolerance.
The “passive” in passive tolerance means that either no cells will recognize the antigen that is tolerated, or the response against it is stopped just after the recognition. Passive tolerance is further divided into two parts: the central and the peripheral tolerance.


=== Central tolerance ===
The central tolerance is established by the negative selection of both T and B-cells. By killing off almost every single developing lymphocyte that would recognize self-antigens, we make sure that none or very few of the fully developed lymphocyte can recognize these antigens. This is accomplished by negative selection of both T and B-cells. T-cells are negatively selected in the thymus, but what about B-cells? Recall that B-cells develop in the bone marrow. The bone marrow has a steady blood flow, so the developing B-cells will be in contact with blood and all the antigens that can be found in it. If any of these developing B-cells recognize and bind any antigen found in the blood, they will be killed by apoptosis. This is the negative selection of B-cells in the bone marrow.
The central tolerance is established by the negative selection of both T and B-cells. By killing off almost every single developing lymphocyte that would recognize self-antigens, we make sure that none or very few of the fully developed lymphocyte can recognize these antigens. This is accomplished by negative selection of both T and B-cells. T-cells are negatively selected in the thymus, but what about B-cells? Recall that B-cells develop in the bone marrow. The bone marrow has a steady blood flow, so the developing B-cells will be in contact with blood and all the antigens that can be found in it. If any of these developing B-cells recognize and bind any antigen found in the blood, they will be killed by apoptosis. This is the negative selection of B-cells in the bone marrow.


However, nothing is perfect and that counts for negative selection as well. It cannot eliminate all self-reacting lymphocytes. That’s why we also have a peripheral tolerance, to complement the central tolerance.
However, nothing is perfect and that counts for negative selection as well. It cannot eliminate all self-reacting lymphocytes. That’s why we also have a peripheral tolerance, to complement the central tolerance.


=== Peripheral tolerance ===
The peripheral tolerance involves keeping some antigens out of reach for the immune system, so that the lymphocytes cannot even meet the antigens in the first place. This is seen in the case of the eyeball and inside the blood-testis barrier created by the Sertoli cells in the testis. These parts of the body are totally separated from the immune system in every healthy person. If there would be physical damage to either the eye or the blood-testis barrier, immune cells could start entering these tissues, where they would start an immune reaction against them. This can cause blindness or infertility.
The peripheral tolerance involves keeping some antigens out of reach for the immune system, so that the lymphocytes cannot even meet the antigens in the first place. This is seen in the case of the eyeball and inside the blood-testis barrier created by the Sertoli cells in the testis. These parts of the body are totally separated from the immune system in every healthy person. If there would be physical damage to either the eye or the blood-testis barrier, immune cells could start entering these tissues, where they would start an immune reaction against them. This can cause blindness or infertility.
[[File:Immunological self-tolerance in normal self tissue.png|thumb|323x323px|This figure shows how the anti-inflammatory environment (like the pancreatic islets) don’t induce APCs into expressing B7.]]
[[File:Immunological self-tolerance in normal self tissue.png|thumb|323x323px|This figure shows how the anti-inflammatory environment (like the pancreatic islets) don’t induce APCs into expressing B7.]]