Immune System

The immune system is an elaborate network of cells, tissues, and organs that helps to protect the body from invaders (bacteria, viruses, fungal infections, and parasites). Usually, the immune system develops only to act upon foreign substances, and immune system cells that try to combat cells of the body are weeded out during the development process. However, in lupus and other autoimmune diseases, the immune system begins to recognize and attack “self.” In other words, the cells of the immune system begin to injure the body’s own tissues. This phenomenon is similar to “friendly fire” and can cause permanent scarring that ultimately jeopardizes the function of certain organs and systems in the body. Certain cells and processes of the immune system have been identified as playing a role in lupus.

T-cells, B-cells, and Antibodies

A group of white blood cells called lymphocytes plays a key role in the human immune response. Lymphocytes include cells called B-cells and T-cells that are responsible for flagging and fighting infections in healthy individuals.

Antigens are substances that elicit the response of T-cells and B-cells in the body. When a T-cell recognizes a specific antigen, it binds to the substance and produces chemicals called cytokines. Cytokines then cause B-cells to multiply, and some of these B cells turn into plasma cells that secrete antibodies (immunoglobulins).  [The response of B cells is referred to as the “humoral” response; T-cell activation is called the “cell-mediated” immune response.] These antibodies then circulate in the bloodstream so that when they encounter the antigen again, they bind to it, forming a complex that is then acted on by other cells of the immune system in an effort to destroy the invader. Usually, remnants of these complexes are removed from the body by a garbage disposal system that involves the spleen.

T-cells are classified as killer-T cells, helper-T cells, or suppressor T-cells. Killer-T cells have the ability to recognize and destroy infected cells in the body. Helper-T cells, however, can only identify viruses engulfed by special cells called macrophages. The macrophage presents the antigen to the helper-T cell, which responds by producing the cytokines that stimulate B cells to multiply and release antibodies.

In healthy individuals, the masses of cells that gather at an infected or injured site in the body produce factors that help fight off the infection. This process causes some inflammation and injury of healthy tissue, but usually the immune system possesses other factors that help to control this inflammatory process. In individuals with lupus, both B cells and T cells become overactive. The two main consequences of this increased activity are the production of autoantibodies (antibodies that recognize and destroy the body’s own cells) and inflammation that can lead to long-term, irreversible scarring.

The production of autoantibodies in people with lupus and other autoimmune diseases causes the immune system to target the body’s own cells for destruction. For example, about 98% of people with lupus possess antinuclear antibodies (ANA), which can attack the nucleic material of your cells. In addition, some individuals may possess anti-phospholipid antibodies, which damage proteins bound to phospholipids in the membranes of your cells. These autoantibodies are linked to pregnancy complications, stroke, heart attacks, and other blood clots.

In addition, regulatory T cells, which are supposed to control the system, are deficient in SLE.

Neutrophils

Neutrophils are the most common type of white blood cell in your body; whereas lymphocytes are involved in the ongoing immune response, neutrophils are the first line of attack against invaders. Inflammation in a healthy individual usually signals that the body’s immune system is responding appropriately to pathogens, damaged cells, irritants, or injury. However, in lupus, neutrophils cause increased inflammation due to certain interactions between an individual’s blood plasma and other immune system cells (specifically, complement, cytokines, and cell adhesion molecules). Even though increased inflammation may cause pain and discomfort, the major problem with inflammation is potential long-term irreversible scarring. It is important that you and your doctor discuss medications to curb the inflammatory processes involved in lupus in order to minimize long-term damage to important organs.

Cytokines

Cytokines are signaling molecules involved in regulation of an individual’s immune response. Some cytokines amplify the immune response, while others tone it down. Some people with lupus and similar autoimmune diseases have a greater ratio of proinflammatory to anti-inflammatory cytokines than normal individuals, which produces an unbalanced regulatory mechanism.

While an overall cause-and-effect relationship between cytokines and lupus is not yet understood, certain cytokines called interferons and interleukins are associated with the disease. In general, however, the overproduction of such molecules causes the immune system to become overactive, leading to increased inflammation and tissue injury.

Complement

Complement proteins interact in a sequential manner to clear immune complexes from your body. Deficiencies of certain complement proteins are associated with lupus. In addition, since complement proteins are consumed during inflammatory processes, low complement levels may indicate lupus activity.

Sources

  • Dean, Gillian S., et al. “Cytokines and systemic lupus erythematosus.” Ann Rheum Dis 2000; 59: 243–251.
  • Wallace, Daniel J. The Lupus Book: A Guide for Patients and Their Families. 1st ed. New York: Oxford University Press, 1995.