Auto-immune diseases

General information

Basically, the immune system does not react to host cells. This is because it exhibits immunologic tolerance. Its ability to discriminate self from non-self is one of its cardinal features. If this is partially/fully lost, then you get self antigen reactions leading to autoimmunity  autoimmune diseases.

Autoimmune disease (Abbas pp 168)

Mechanism of Tolerance

Tolerance is divided up into central and peripheral. Before this, you should understand what happens when an antigen is presented to a lymphocyte.

1. It may be activated, in which case the antigen is said to be “immunogenic”,
2. It may be inactivated or killed, in which the antigen is said to be “tolerogenic”,
   
3. It may just ignore the antigen and not respond nor get inactivated/killed, called ignorance. Microbes are immunogenic, self antigens are tolerogenic/ignorance.

Immunologic tolerance, therefore, can be induced either when lymphocytes are maturing in lymphoid organs called central tolerance, or when they are matured and come into contact with self antigens called peripheral tolerance.

Peripheral Tolerance (Abbas pp 169 + 176)

If immature lymphocytes have receptors that strongly interact with self antigens within the thymus (T cells)/bone marrow (B cells), then signals are given that kill the lymphocyte. This process is termed negative selection. Peripheral tolerance has three mechanisms, and is generally recognised as when a mature T cell recognises a self antigen in peripheral tissues – but 1) get inactivated (anergy) 2) die 3) active suppression.

• Anergy: this is when T cells get inactivated when they interact with antigens without adequate co-stimulators. (i.e.: 2^nd signal not present). The costimulators are expressed on APCs.

• Deletion: If T cells get repeatedly activated by self antigens, then they induced into apoptosis, so autoreactive T cells get deleted.

• Immune suppression: Upon interaction with a self antigen, some T cells suppress themselves from activation and also regulate the inactivation of other potential autoreactive T & B cells.

Spectrum of Autoimmune diseases (Notes, Abbas pp 263)

Organ specific vs Non-organ specific

Autoimmune diseases can be split up into organ specific vs non-organ specific. An example of an organ specific disease is thyroditis where thyroglobulin is the antigen. Organ specific autoimmune diseases is when antigen is found in one particular organ (i.e.: thyroglobulin is only found in the thyroid). An example of a non-organ specific autoimmune disease is rheumatoid arthritis or SLE. This is when antigen is spread throughout the body, therefore immune complexes are deposited everywhere (usually spread by blood stream).

There is considerable overlap between these two categorises.

Category: Pathology Notes