How the Immune System Works
The immune system defends the body from attack by “invaders” recognized as foreign. It is an extraordinarily complex system that relies on an elaborate and dynamic communications network that exists among the many different kinds of immune system cells that patrol the body. At the “heart” of the system is the ability to recognize and respond to substances called antigens whether they are infectious agents or part of the body, which are called self anitgens.
T and B Cells
Most immune system cells are white blood cells, of which there are many types. Lymphocytes are one type of white blood cell, and two major classes of lymphocytes are T cells and B cells. T cells are critical immune system cells that help to destroy infected cells and coordinate the overall immune response. The T cell has a molecule on its surface called the T-cell receptor. This receptor interacts with molecules called MHC or major histocompatibility complex. MHC molecules are on the surfaces of most other cells of the body and help T cells recognize antigen fragments. B cells are best known for making antibodies. An antibody binds to an antigen and marks the antigen for destruction by other immune system cells. Other types of white blood cells include macrophages and neutrophils.
Macrophages and Neutrophils
Macrophages and neutrophils circulate in the blood and survey the body for foreign substances. When they find foreign antigens, such as bacteria, they “engulf” and destroy them. Macrophages and neutrophils destroy foreign antigens by making toxic molecules such as reactive oxygen intermediate molecules. If production of these toxic molecules continues unchecked, not only are the foreign antigens destroyed, but tissues surrounding the macrophages and neutrophils are also destroyed. For example, in individuals with the autoimmune disease called Wegener’s granulomatosis, overactive macrophages and neutrophils that invade blood vessels produce many toxic molecules and contribute to damage of the blood vessels. In rheumatoid arthritis, reactive oxygen intermediate molecules and other toxic molecules are made by overproductive macrophages and neutrophils invading the joints. The toxic molecules contribute to inflammation, which is observed as warmth and swelling, and participate in damage to the joint.
MHC and Co-Stimulatory Molecules
MHC molecules are found on all cell surfaces and are an active part of the body’s defense team. For example, when a virus infects a cell, a MHC molecule binds to a piece of a virus or antigen, and displays the antigen on the cell’s surface. Cells that have the capability of displaying antigen with MHC are called antigen-presenting cells. Each MHC molecule that displays an antigen is recognized by a matching or compatible T-cell receptor. Thus, an antigen-presenting cell is able to communicate with a T cell about what may be occurring inside the cell.
However, for the T cell to respond to a foreign antigen on the MHC, another molecule on the antigen-presenting cell must send a second signal to the T cell. A corresponding molecule on the surface of the T cells recognizes the second signal. These two secondary molecules of the antigen-presenting cell and the T cell are called co-stimulatory molecules. There are several different sets of co-stimulatory molecules that can participate in the interaction of antigen-presenting cell with a T cell.
Once the MHC and the T-cell receptor interact, and the co-stimulatory molecules interact, there are several possible paths that the T cell may take. These include T cell activation, tolerance, or T cell death. The subsequent steps depend in part on which co-stimulatory molecules interact and how well they interact. Because these interactions are so critical to the response of the immune system, researchers are intensively studying them to find new therapies that could control or stop the immune system attack on self tissues and organs.
Cytokines and Chemokines
One way T cells can respond after the interaction of the MHC and the T-cell receptor, and the interaction of the co-stimulatory molecules, is to secrete cytokines and chemokines. Cytokines are proteins that may cause surrounding immune system cells to become activated, grow, or die. They also may influence non-immune system tissues. For example, some cytokines may contribute to the thickening of the skin that occurs in people with scleroderma.
Chemokines are small cytokine molecules that attract cells of the immune system. Overproduction of chemokines contributes to the invasion and inflammation of the target organ, which occurs in autoimmune diseases. For example, overproduction of chemokines in the joints of people with rheumatoid arthritis may result in invasion of the joint space by destructive immune system cells such as macrophages, neutrophils, and T cells.
B cells are another critical type of immune system cell. They participate in the removal of foreign antigens from the body by using a surface molecule to bind the antigen or by making specific antibodies that can search out and destroy specific foreign antigens. However, the B cell can only make antibodies when it receives the appropriate command signal from a T cell. Once the T cell signals the B cell with a type of cytokine that acts as a messenger molecule, the B cell is able to produce a unique antibody that targets a particular antigen.
Immune Complexes and the Complement System
When many antibodies are bound to antigens in the bloodstream, they form a large lattice network called an immune complex. Immune complexes are harmful when they accumulate and initiate inflammation within small blood vessels that nourish tissues. Immune complexes, immune cells, and inflammatory molecules can block blood flow and ultimately destroy organs such as the kidney. This can occur in people with systemic lupus erythematosus.
A group of specialized molecules that form the complement system helps to remove immune complexes. The different types of molecules of the complement system, which are found in the bloodstream and on the surfaces of cells, make immune complexes more soluble. Complement molecules prevent formation and reduce the size of immune complexes so they do not accumulate in the wrong places such as organs and tissues of the body. Rarely, some people inherit defective genes for a complement molecule from their parents. Because these individuals cannot make a normal amount or type of complement molecule, their immune systems are unable to prevent immune complexes from being deposited in different tissues and organs. These people develop a disease that is not autoimmune but resembles lupus erythematosus.
Genetic factors can affect an individual’s immune system and its responses to foreign antigens in several ways. Genes determine the variety of MHC molecules that individuals carry on their cells. Genes also influence the potential array of T-cell receptors present on T cells. In fact, some MHC genes are associated with autoimmune diseases. However, genes are not the only factors involved in determining a person’s susceptibility to an autoimmune disease. For example, some individuals who carry disease-associated MHC molecules on their cells will not develop an autoimmune disease.