Before concluding our discussion of the mechanisms of immunologic tolerance, it is useful to consider two other types of antigens that are not self but are produced by cells or tissues that have to be tolerated by the immune system. These are products of commensal microbes that live in symbiosis with humans and paternally derived antigens in the fetus. Coexistence with these antigens is dependent on many of the same mechanisms that are used to maintain peripheral tolerance to self antigens.

Tolerance to Commensal Microbes in the Intestines and Skin

 The microbiome of healthy humans consists of approximately 10¹⁴ bacteria and viruses (which is estimated to be almost 10 times the number of nucleated human cells, prompting microbiologists to point out that we are only 10% human and 90% microbial!). These microbes reside in the intestinal and respiratory tracts and on the skin, where they serve many essential functions. For instance, in the gut, the normal bacteria aid in digestion and absorption of foods and prevent overgrowth of potentially harmful organisms. Mature lymphocytes in these tissues are capable of recognizing the organisms but do not react against them, so the microbes are not eliminated, and harmful inflammation is not triggered.

In the gut, several mechanisms account for the inability of the healthy immune system to react against commensal microbes. These mechanisms include an abundance of IL-10– producing regulatory T cells, and an unusual property of intestinal dendritic cells such that signaling from some Toll-like receptors leads to inhibition rather than activation. In addition, many commensal bacteria are physically separated from the intestinal immune system by the epithelium. The mechanisms that maintain tolerance to commensal bacteria in the skin are not as well defined.

Tolerance to Fetal Antigens

 The evolution of placentation in eutherian mammals allowed the fetus to mature before birth but created the problem that paternal antigens expressed in the fetus, which are foreign to the mother, have to be tolerated by the immune system of the pregnant mother. One mechanism of this tolerance is the generation of peripheral FoxP3+ regulatory T cells specific for these paternal anti gens. In fact, during mammalian evolution, placentation is strongly correlated with the ability to generate stable peripheral regulatory T cells. It is unclear whether women who suffer recurrent pregnancy losses have a defect in the generation or maintenance of these regulatory T cells. Other mechanisms of fetal tolerance include exclusion of inflammatory cells from the pregnant uterus, poor anti gen presentation in the placenta, and an inability to generate harmful Th1 responses in the healthy pregnant uterus.

Now that we have described the principal mechanisms of immunologic tolerance, we consider the consequences of the failure of self-tolerance—namely, the development of autoimmunity.

مواضيع ذات صلة

الحساسية الدوائية نحو العوامل المخصرة للوصل العَصَبِي العَضَلِي

آليات حساسية السلفوناميدات ومظاهرها

Antigen - Antibody Interaction: Specificity and Cross - Reactivity

ANTIBODY SYNTHESIS

B Lymphocyte Tolerance

Peripheral T Lymphocyte Tolerance

Immune Memory

B Cells

T Cells

إزالَةُ التَحسس نحو البنسلين Penicillin Desensitization

الحساسية نحو البنسلين

الفرق بين فَرْطُ التحسس والحساسية الدوائية