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Pathology => Immune System

Immune System

Immune System, the body system that is primarily responsible for destroying the disease-causing agents that it encounters. (Any agent perceived as foreign by a body's immune system is called an antigen.) The responsibility of the immune system is immense, and it must encompass a vast diversity in order to react appropriately with the thousands of different and potentially disease-causing antigens that invade the body. The complex physiological mechanisms involved in the immune system are not yet fully understood, but they continue to be unravelled by ongoing medical research.

The immune system has six major components, three of which are different kinds of cells and three of which are soluble proteins. All six components can be found circulating in the blood in some form.

° Cells
The three broad categories of immune cells are granulocytes, monocyte/macrophages, and lymphocytes. Granulocytes are the most numerous nucleus-containing cells in the blood. They phagocytize (ingest) antigens entering the body, particularly when the antigens have been coated by immunoglobulin or complement proteins in the blood (described below, under Proteins). Once ingested, the antigens normally are destroyed by potent enzymes usually present in the granulocytes.
Monocytes are only a small percentage of the many kinds of blood cells; when found localized outside the blood circulation, in tissues, they undergo physical and morphological changes and are called macrophages. Like granulocytes, they ingest foreign substances, interact with immunoglobulin and complement proteins, and carry potent enzymes in their cytoplasm. In addition, however, monocytes alter the antigens in a way that makes the immune response of the third kind of immune cell-the lymphocytes-easier and more effective.
Lymphocytes are, in some respects, the most important cells in the immune system. Two major kinds exist: B lymphocytes and T lymphocytes. The former are responsible for humoral, or serum, immunity; that is, they and their direct descendants, called plasma cells, are the cells responsible for the production of the blood-serum components called immunoglobulins (see below). The T lymphocytes are responsible for cellular immunity; that is, they attack and kill antigens directly. They also amplify or suppress the overall immune response by regulating the other components of the immune system, and they secrete a wide range of cytokines (see below). T lymphocytes make up perhaps 70 per cent of all lymphocytes. Both they and the B lymphocytes have the ability, biochemically, to "remember" previous exposure to a specific antigen, so that upon repeated exposure a more effective destruction of the antigen can take place.

° Proteins
The three kinds of proteins in the immune system, found dissolved in the serum (the liquid portion of the blood), are immunoglobulins, cytokines, and complement proteins. Literally thousands of different kinds of immunoglobulins, called antibodies, occur, and each of them combines exactly with one specific kind of antigen and helps remove it from the body. This immense diversity characterizes the immune system as a whole.
Cytokines are soluble components that are largely responsible for regulating the immune response. If secreted from lymphocytes, they are called lymphokines; if secreted by monocytes, they are called monokines. Some cytokines amplify or increase an ongoing immune response; others instruct cells to proliferate; and still others may suppress an ongoing response. The immune system, like many other body systems, must be regulated in this way so that it is active when appropriate but not pathologically overactive.
The complement proteins are a family of components that act in concert with one another and with immunoglobulins to help in developing a proper immune response. When an antibody binds to its antigen, the complement proteins may then bind to the complex thus formed, facilitating phagocytosis by immune cells.

The six immune system components described above act in concert to develop an effective immune response. Many of the steps involved in this process have been documented by research studies; others are under active investigation but still remain speculative. Typically, however, if a disease-causing antigen such as a bacterium breaches the first line of body defence-for example, the skin-it might first encounter granulocytes and monocytes and be partly neutralized by preformed antibodies and complement proteins. Lymphocytes and macrophages then interact at the invasion site, amplifying the immune response; more specific and effective antibodies are developed, as is a biochemical "memory" of the invading bacterium. Similar amplification of the immune response may take place in the nearest lymph nodes (seeLymphatic System), as well as in more distant sites of lymphocyte formation such as the spleen and bone marrow.
At some point, if all goes well, the immune system overtakes the bacterium so that the disease is under control. Suppressive, self-regulatory mechanisms then come into play to shut down the immune response; the cytokines are especially important in this suppressive process. (If the immune system is not properly self-regulated in this way, other diseases, of an immunopathological nature, can ensue.) Once the antigen is destroyed by this combination of actions, the immune system is primed to respond more effectively if that same kind of micro-organism should invade again. If the priming is adequate to neutralize a specific bacterium totally before it causes disease, specific immunity to that bacterium is then said to exist.

Certain clinically important diseases are related primarily to deficiencies of the immune system, and others are related to an abnormally functioning (but not otherwise deficient) immune system. Failure or deficiency of the system can be a primary phenomenon-that is, congenital or acquired-or it can occur secondarily as a consequence of other diseases, such as cancer. Immunosuppression may also occur subsequent to treatment for other diseases, including cancer.
Primary immunodeficiencies are usually congenital and range from mild abnormalities to severe deficiencies incompatible with life. Failure of B lymphocytes and absence of antibodies are relatively common problems, affecting perhaps one in 500 people, and are usually associated with recurrent infections (primarily with bacteria). This type of failure frequently can be treated with monthly injections of gamma globulin, which contains many protective antibodies. Failures of T lymphocyte function and cellular immunity are much less common than antibody-related deficiencies; they are primarily associated with viral and fungal infections and are less amenable to treatment. The most severe primary immunodeficiencies involve a combined deficiency of both B cells and T cells; virtually all of these are fatal without radical treatment, such as bone-marrow transplantation. In recent years the acquired immunodeficiency that has drawn the greatest public attention is acquired immune deficiency syndrome (AIDS).
Secondary immunodeficiencies can be induced by toxic drugs (such as those used in cancer treatment) or by malnutrition, or they can be secondary to other diseases (for example, cancer). They range from mild to severe, can be B-cell- or T-cell-related diseases, and are best treated by alleviation of the primary problem.
Many diseases generally classified as autoimmune diseases are probably due to faulty self-regulation of the normal immune response. The faulty system can destroy or injure normal cells and normal soluble substances, leading to clinically apparent disease. An allergy is an abnormal reaction to a previously encountered substance that is usually inoffensive to others.

Although the immune system is essential for human survival, it presents an obstacle in clinical organ transplantation. The normal immune system is effective at recognizing cells from another individual as foreign. Once the system recognizes these cells, it will attempt to destroy them; without immunosuppressive medication such as cyclosporin, transplanted kidneys, livers, and bone marrow will be rejected. As might be predicted, however, the immunosuppressive therapy can itself lead to problems with infections. Thus, the patient under treatment is constantly in danger of either infection or rejection.

For many years a great deal of interest has focused on the relationship between the immune system and cancer. Cancer patients have an increased rate of infection, and immunological abnormalities can be seen in laboratory studies of cells and serum from some of these patients. Conversely, the incidence of cancer is much higher than would otherwise be expected both in patients with primary immunodeficiencies and in patients on immunosuppressive therapy. Also, increasing the response of the immune system by therapeutic intervention in patients with cancer has led to some limited positive effects. Manipulation of the immune response and the development of immunologically based treatment will undoubtedly have a positive impact on attempts to treat cancer.

The immune system continues to be a fertile area of research. One major area of interest is the study of how the immense diversity of the immune system evolves. Another is the analysis of the relationship between specific clinical diseases and faulty immunoregulation. Research efforts are being devoted to finding ways of manipulating the immune response-not only to treat immunodeficiency diseases but also to improve results in clinical transplantation and cancer. The identification of the receptor molecule by which T cells recognize antigens, and the cloning of the interleukin-2 receptor gene in the early 1980s, were significant developments in this ongoing research.