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How The Immune System Works
An analogy to help us understand the complexities of the immune system is to think of it as an army that lives inside the body to protect from invaders. These invaders, called foreign antigens can be in the form of bacteria, virus, fungi, parasites or even single proteins. The cells of the immune system are its soldiers and the organs and tissues are the barracks where the cells live until an antigen invades. There are also cells that constantly patrol the body through the blood stream looking for foreign antigens.
Once a foreign antigen is detected the immune system attacks and destroys it. If the body is strong, it can win the battle most of the time. When a major component of the immune system is not functioning correctly, medical intervention is necessary to stay healthy and ward off infections.
The Dynamics of the Immune System
The cells that make up the immune system develop in the bone marrow in the form of the stem cells. These develop into cells called B-lymphocytes, T-lymphocytes and phagocytes. These three primary cell families and the proteins they produce make up the soldiers and ammunition of the immune system. These cells and proteins are all spread throughout the body so they can react quickly to any problem.
Adaptive Immunity vs. Innate Immunity
The immune system utilizes two types of effectors functions: innate and adaptive. Innate effector functions are comprised of cells (phagocytes) and proteins (complement, mannose binding protein and other related proteins) that attack foreign antigens immediately, even when seeing them for the first time. These cells and proteins are ready to go at birth and do not form any memory of foreign antigens. Adaptive effector functions are comprised of cells (lymphocytes) and proteins (antibodies) that are specifically targeted to a particular foreign antigen. Adaptive responses are slow on the first encounter with a foreign antigen, but they form memory and increase in both speed and effectiveness with each subsequent encounter.
When a foreign antigen invades the body T-helper cells direct B-lymphocytes or B-cells to make antibodies against it. These Antibodies bind to the foreign antigen, neutralizing it and allowing phagocytes to digest and eliminate it completely. Problems within B-cells typically manifest as antibody deficiencies that may become clinically relevant as early as seven to nine months of age, at a time when maternal antibodies passed through the placenta during pregnancy have fallen to non-protective levels. Some antibody deficient states (common variable immunodeficiency) may not manifest themselves until the second or third decades of life.
Diseases Associated with B-Lymphocyte Dysfunction
Treatment of B-lymphocyte/Antibody Deficient Disorders
Treatment of these disorders has been revolutionized by the availability of concentrated intravenous immunoglobulin preparations (IVIG). Infusions with IVIG at three to four week intervals replaces the antibodies that patients are unable to make on their own, allowing maintenance of normal function without the morbidity associated with recurrent infections.
There are three main forms of T-lymphocytes: Natural killers (NK cells), Helpers (T-helper cells) and suppressors (T-suppressor cells). NK cells attack antigens directly. T-helpers direct and assist all other immune cells in attacking foreign antigens. T-suppressors are the off-switch to an attack. They serve to limit collateral damage. T-cells direct the rest of the immune system to respond to foreign invaders; therefore, problems in the T-lymphocyte system are generally profound causing severe combined immunodeficiency syndromes (SCID) that declare themselves soon after birth. Severe combined immunodeficiency (SCID) is a pediatric emergency requiring bone marrow transplant for any chance at survival. Milder forms of T-lymphocyte dysfunction (combined immunodeficiency - CID) may present later in life, are generally milder and may be managed by supportive measures rather than bone marrow transplant.
Treatment of T-lymphocyte Disorders (SCID & CID)
Treatment of SCID is confined to bone marrow transplant. Treatment of CID may in some cases require a bone marrow transplant but may be managed by supportive care alone.
There are several types of phagocytes including monocytes, macrophages and polymorphonuclear leucocytes. Phagocytes finish the destruction of foreign antigens initiated by antibody neutralization. These cells are very important in fighting infection and while the lymphocytes can be seen as the generals and commanders of the army, the phagocytes are the foot soldiers and without them any war will soon be lost. One of the most severe forms of phagocyte dysfunction is Chronic Granulomatous Disease that typically manifests in the first years of life with recurrent pneumonia. Milder forms such as cyclic neutropenia may go undetected into adulthood.
The Compliment System and Related Proteins
The compliment system and related proteins (i.e. Mannose Binding Protein) function very similar to antibodies. They bind to foreign antigens and enable other cells like phagocytes to eliminate them. They are preformed and ready to go; they do not require the interaction of T-helpers or B-cells to be produced like antibodies do. They are not nearly as effective as antibodies. Deficiencies in this system typically cause problems early in life before sufficient amounts of antibodies can be made.
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