A behind-the-scenes look at the nebulous sect of autoimmune diseases, with a spotlight on MS

Autoimmune diseases are highly complex and not completely understood. For many autoimmune diseases there is little in the way of treatments. Often the complete etiology of the disease is unknown, thus treatments, when available, are often incomplete, leaving the individual with symptoms related to the disease. As autoimmune diseases are exceedingly complex, our inquiry must begin with a basic understanding of the normally functioning immune system. The immune system exists to defend against pathogens. These pathogens include viruses, bacteria, parasites, allergens, malignant cells and harmful chemical agents. The immune system has three important characteristics:

1. Diversity and specificity. This is the ability to recognize a wide variety of pathogens with both a general and specific response.
2. Memory. This is the ability to rapidly recognize a previously encountered pathogen.
3. The ability to distinguish self from non-self. This prevents autoimmue responses.

The immune system defends on several levels. The first is through system barriers, like the walls of a castle. The skin, the mucous membranes and the cornea of the eye provide a barrier to invading pathogens. Yet these barriers are inadequate for all pathogens; the immune system also has complex mechanisms of defense at the cellular level.

CELLULAR BACKGROUND

Cells of the immune system are generated in the bone marrow and mature either in the bone marrow (B-cells) or thymus (T-cells). The immune system has two major branches: innate and acquired immunity. Innate immunity is inborn, nonspecific and does not require any previous exposure to become activated. It provides a very rapid response to a pathogen. Inflammation is one innate immune response. Phagocytic cells comprising circulating neutrophils and monocytes circulate and respond to pathogens. In addition, NK (natural killer) cells have the ability to kill viral infected cells. Finally certain antibodies are activated with innate immunity and respond along with a series of proteins, known as complement, to a pathogen. Innate immunity does not have any memory of exposure.

Acquired or adaptive immunity becomes activated with exposure to a pathogen. Adaptive immunity provides a more specific response to a pathogen and also has memory of the exposure so that a subsequent exposure has a more immediate response. Acquired immunity can be divided into two parts: cell-mediated and humoral immunity. Both involve lymphocytes that originate in the bone marrow. Cell-mediated immunity involves T-cells that mature in the thymus and humoral immunity involves B–cells (that mature in the bone marrow), T-cells, antibodies and complement.

Both B- and T-cells have receptors on their cell surface that recognize pathogens. T-cells are not able to recognize the entire pathogen and must be presented with a piece of the pathogen or antigen in order to become activated. This presentation is accomplished by specific cells such as macrophages and dendritic cells that engulf and process a pathogen. A small fragment of the pathogen, now known as an antigen, is displayed on the cell surface by a surface molecule known as a major histocompatibility complex. T-cells are only able to recognize and respond to antigens presented in this way. Different types of T-cells respond to specific MHC types. Once the T-cell recognizes the properly displayed antigen, under the influence of multiple chemicals such as interferons and cytokines, the T-cell will become activated and proliferate. T-cells are also known as helper cells. There are two major varieties: Th-1 and Th-2 cells.

Through the release of additional substances, activated T-cells are able to amplify and direct the immune response to the antigen. Activated T-cells enhance the activity of macrophages and NK cells. In addition, they help activate B-cells. Activated T-cells in circulation are able to migrate into tissues by adherence to the blood vessel endothelium and migration through to the tissue. T-cells orchestrate an immune response through recruitment and activation of other immune system cells. B-cells are involved with the immune response, but in a different way than T-cells. The receptor on the B-cell that recognizes a pathogen is an antibody molecule. It does not require any specialized presentation and recognizes the pathogen in its entirety. B-cells express specific antibodies, but each B-cell does not express all antibodies. Thus, there is specificity with the B-cell response. Activated B-cells give rise to plasma cells that can make large quantities of antibodies. Antibodies destroy pathogens by various mechanisms, including making them more susceptible to phagocytosis, and by the activation of complement.