Mechanisms of Autoimmunity (1)
Pathological Immune Mechanisms and Tolerance
A. Induction of Autoimmune Response by Virally Induced T-Cell Activation
Autoreactive T cells cannot be activated by target cells in the absence of a co stimulatory signal . Tcell activation and destruction of the target cells can only occur after the antigen has been presented to the T cells by professional" antigen presenting cells (APCs). e.g., in infection. The previously described experiment produced double transgenic mice with T cells that all bore the same T cell receptor directed against a lymphocytic choriomeningitis virus (LCMV) protein.
The gene for the viral protein was additionally linked to the insulin promoter and introduced into animals of the same strain. Hence, all islet cells expressed this protein via their MHC molecules.
In theory. the islet cells should have been killed quickly since they all bore a molecule recognized by cytotoxic T cells. In practice. however, prenatal tolerance did not develop because the transgenic gene product apparently had not entered the thymus.
No T cell reaction occurred, and the animals did not develop diabetes-mellitus. Direct infection of the animals with the LCM virus. on the other hand. led to T cell activation and destruction of islet cells. Only then did the cytotoxic T cells receive a (co stimulatory) signal via antigen presenting cells and activated T helper cells.
B. Induction of Antibody Formation with T Cell Help after Autoantibodymediated Antigen Presentation
Auto-reactive B cells cannot be activated to form antibodies without the help of T cells. With the help of their cell based immunoglobulin, how ever. they are able to recognize. bind, process. and present molecules containing endogenous antigen (auto-antigen) and foreign antigen components.
Once such an antigen has been processed, the B cells present the foreign component of the antigen to T cells via their MHC molecule. The T cells then transmit signals for B cell help. In this case, the B cells are those that recognize an auto-antigen and, thus, secrete the corresponding auto-antibodies.
C. Induction of Autoimmunity via Molecular Mimicry
According to the molecular mimicry hypothesis. a certain antigen, such as a viral or bacterial antigen, has a great degree of similarity with
endogenous structures. Because of mistaken identity, the body then attacks foreign as well as endogenous molecules when infected with the antigen.
D. Induction of an Autoimmune Reaction after Viral Infection due to Aberrant MHC Class II Antigens
In many autoimmune diseases, HLA class ll antigens are found on target cells that do not exhibit the corresponding cell systems in healthy individuals.
lFN 7 related induction could be a possible mechanism in such aberrant" class II antigen expression. A virus infects a certain cell group, and its surface molecules are identified as foreign by specific T lymphocytes.
During the defense process. the T lymphocytes secrete lFN 1. which leads to the induction of class ll antigens in previously un-involved cells. This aberrant" expression of class II antigens might prompt auto-reactive T cells. in association with class [I antigens that are not normally expressed, to identify auto-antigens on the cell surface as foreign and. ultimately, to destroy endogenous cells.
