Immune System Involvement In Psoriasis

In 1979, researchers coincidentally found that a drug–cyclosporine–that suppresses the immune system in bone marrow transplant patients also cleared psoriasis. Since then, psoriasis has been widely accepted as a disease that is involved with the immune system. The study of the immune system is called immunology.
How does the immune system affect psoriasis?A normal immune system protects the body against "invaders" by destroying bacteria, viruses and other foreign proteins. In the person who has psoriasis, the immune system "misfires" and inappropriately causes inflammation and an accelerated growth of skin cells.
The skin cells reproduce too quickly and the skin (and the joints in some people) becomes inflamed. Many steps in this misfired immune response are targeted by old and new treatments. One goal of treatment is to block or modify the response by focusing on very specific immune cells, thus avoiding widespread effects on the rest of the body.
For example, methotrexate (a prescription systemic medication used to treat psoriasis) binds to an enzyme involved in the rapid growth of cells that is triggered by the immune system response in psoriasis. But methotrexate affects other systems in the body, too. New drugs, called biologics, have been designed to target very specific parts of the immune system response. For more information about this class of treatments, see the biologics section.
Many of today's psoriasis treatments, including cyclosporine and methotrexate, are believed to work because they affect the immune system. However, newer drugs may be "smarter" in that they target specific immune responses, not the entire immune system. Because they are new, long-term effects of these drugs are essentially unknown.
What is the role of T cells?Psoriasis is frequently referred to as a "T-cell mediated disease." T cells are a type of immune system cell (white blood cell) that have been shown to be very important in the internal process of psoriasis. T cells naturally circulate throughout the body looking for antigens, or foreign substances. The presence of the antigen, usually an outside invader like a bacterium or virus, activates the T cell, which then initiates an immune response to neutralize the antigen.
In psoriasis, activated T cells end up in the skin. It is not clear why this happens, but it may be directly related to the genetic susceptibility in people who develop psoriasis.
T cells become activated by two necessary interactions.
Interaction One
An antigen-presenting cell (APC) processes and displays an antigen on its surface. A T cell recognizes and targets that antigen. The specific antigen or antigens responsible for psoriasis are not known, but some infections (for example, strep throat) create an antigen believed to trigger some cases of guttate psoriasis.
Interaction Two
When the APC "shows" the antigen to the T cell, other receptors on the APC and T cell must also interact like a lock and key for the T cell to become activated. This lock and key mechanism is called the co-stimulatory pathway.
If T cells are not activated, the immune response and the cycle of psoriasis never get started. If the T cell becomes activated, an immune response is initiated that leads to the development of skin lesions. One part of this response includes the release of cytokines. Cytokines are proteins that the immune system uses to communicate messages. In psoriasis, cytokines tell skin cells to reproduce and mature at an accelerated rate. They also set off other reactions, including inflammation, the activation of additional T cells, the recruiting of T cells into the skin and the release of more cytokines.
The end result is a cycle of skin cells growing too fast, moving to the surface of the skin and piling up as dead cells (the white scale). The top, or epidermal, layer of the skin thickens, and redness develops as blood vessels expand and multiply, and blood flow to the skin increases.
How is the immune system modulated?The lock and key sets, or co-stimulatory pathways, are a good target for new psoriasis drugs to short-circuit psoriasis. Beyond that, other immune system cells involved in psoriasis are also a focus of drug development.
For example, some cytokines carry inflammatory messages and help fuel the overall immune response in the skin. Some of these cytokines, such as tumor necrosis factor-alpha (TNF-alpha), are targeted to be blocked by several of the biologic treatments now on the market.
On the other hand, some cytokines that normally suppress inflammation are lacking or present only in low levels in psoriatic skin. Scientists have experimented with boosting the levels of these proteins to rebalance the biochemical make-up of the skin.
What lies ahead?Psoriasis research is benefiting from the fact that psoriasis is driven by the immune system and responds to drugs that suppress the body's immune response (immunosuppressive therapy). Many other diseases and medical problems, such as diabetes, lupus and rheumatoid arthritis, are also driven by the immune system. Genes that are associated with psoriasis are also involved with rheumatoid arthritis and lupus. Because psoriasis is easily visible on the skin, the disease provides an excellent model for studying the effectiveness of various medications that might be useful in other diseases that also involve the immune system.