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Autoimmunity - an Introduction

Immune Tolerance and Autoimmunity

In healthy individuals the immune system does not attack the body’s own structures. During lymphocyte development, T and B lymphocytes that recognize self antigens on the surface of somatic cells are deleted before they develop into fully immunocompetent cells, preventing autoimmunity.

In autoimmune disease immune tolerance breaks down. This may occur after an injury or when a great number of cells die and components that are normally hidden in the cell’s interior get into the blood circuit and become accessible to immune cells.

Sometimes proteins that are produced naturally in the body are modified biochemically during an inflammation or by environmental factors. Due to these posttranslational modifications, the immune system takes them for foreign structures. Examples for this tolerance breaking mechanism are the citrullination of proteins in rheumatoid arthritis or the deamidation of gliadin in celiac disease.

Mouse
Fig.1
HLA VIPR Complex

Crystal structure of a human MHC (HLA1)) binding a citrullinated vasoactive intestinal peptide type 1 receptor (VIPR) peptide (PDB code: 3B6S).

HLA class I histocompatibility antigen (B-27 alpha chain): yellow and magenta; beta-2-microglobulin: silver; VIP receptor 1 fragment (residues 400-4008): blue; citrulline: orange.

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