The Immune System / What is The Immune System?

submitted by Dr. Gary Farr Last Updated June, 20, 2002

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The immune system stockpiles a tremendous arsenal of cells. Some staff the general defenses, while others are trained on highly specific targets. To work effectively, however, most immune cells require the active cooperation of their fellows. Sometimes they communicate through direct physical contact, sometimes by releasing versatile chemical messengers.

In order to have room for enough cells to match millions of possible foreign invaders, the immune system stores just a few of each specificity. When an antigen appears, those few specifically matched cells are stimulated to multiply into a full-scale army. Later, to prevent this army from overexpanding wildly, like a cancer, powerful suppressor mechanisms come into play.

Lymphocytes are small white blood cells that bear the major responsibility for carrying out the activities of the immune system; they number about one trillion. The two major classes of lymphocytes are: B cells, which grow to maturity independent of the thymus, and T cells, which are processed in the thymus. Both B cells and T cells recognize specific antigen targets. B cells work chiefly by secreting soluble substances called antibodies into the body's fluids, or humors. (This is known as cellular immunity.) Although small lymphocytes look identical, even under the microscope, they can be told apart by means of distinctive molecules they carry on their cell surface. Not only do such markers distinguish between B cells and T cells, they distinguish among various subsets of cells that behave differently. Every mature T cell, for instance, carries a marker known as T3 (or CD3); in addition, most helper T cells carry a T4 (CD4) marker, a molecule that recognizes class II MHC antigens. A molecule known as T8 (CD8), which recognizes class I MHC antigens, is found on many suppressor/cytotoxic T cells. In addition, different T cells have different kinds of antigen receptors-either alpha/beta or gamma/delta.

 

Each B cell is programmed to make one specific antibody. For example, one B cell will make an antibody that blocks a virus that causes the common cold, while another produces antibody that zeros in on a bacterium that causes pneumonia.

When a B cell encounters its triggering antigen(along with collaborating T cells and accessory cells), it gives rise to many large plasma cells. Every plasma cell is essentially a factory for producing antibody. Each of the plasma cells descended from a given B cell (which are all members of the same family, or clone) manufactures millions of identical antibody molecules and pours them into the bloodstream.

A given antibody matches an antigen much as a key matches a lock. The fit varies: sometimes it is very precise, while at other times it is little better than that of a skeleton key. To some degree, however, the antibody interlocks with the antigen and thereby marks it for destruction.

Antibodies belong to a family of large molecules known as immunoglobulins. Immunoglobulins are proteins, made up of chains of polypeptides, strings of the basic units known as amino acids. Each antibody has two identical heavy polypeptide chains and two identical light chains, shaped to form a Y. The sections that make up the tips of the Y's arms vary greatly from one antibody to another, creating a pocket uniquely shaped to enfold a specific antigen. This is called the variable (V) region. The stem of the Y serves to link the antibody to other participants in the immune defenses. This area is identical in all antibodies of the same class, and is called the constant (C) region.

Scientists have identified nine chemically distinct classes of human immunoglobulins (Ig)-four kinds of IgG and two kinds of IgA, plus IgM, IgE, and IgD. Each type plays a different role in the immune defense strategy. IgG, the major immunoglobulin in the blood, is also able to enter tissue spaces; it works efficiently to coat microorganisms, speeding their uptake by other cells in the immune system. IgM, which usually combines in star-shaped clusters, tends to remain in the bloodstream, where it is very effective in killing bacteria. IgA concentrates in body fluids-tears, saliva, the secretions of the respiratory and gastrointestinal tracts-guarding the entrances to the body. IgE, which under normal circumstances occurs only in trace amounts, probably evolved as a defense against parasites, but it is more familiar as the villain in allergic reactions (Allergy). IgD is almost exclusively found inserted into the membranes of B cells, where it somehow regulates the cell's activation.

Antibodies can work in several ways, depending on the nature of the antigen. Antibodies that interlock with toxins produced by certain bacteria can disable them directly (and are known as antitoxins). Other antibodies, by coating (or opsonizing) bacteria, make the microbes highly palatable to scavenger cells equipped to engulf and destroy them. More often an antigen-antibody combination unleashes a group of lethal serum enzymes known as complement (Complement). Yet other antibodies block viruses from entering into cells (a quality that is exploited in making vaccines). And, in a phenomenon known as antibody-dependent cell-mediated cytotoxicity (ADCC), cells coated with antibody become vulnerable to attack by several types of white blood cells.

T cells contribute to the immune defenses in two major ways. Regulatory T cells are vital to orchestrating the elaborate system. (B cells, for instance, cannot make antibody against most substances without T cell help). Cytotoxic T cells, on the other hand, directly attack body cells that are infected or malignant.

Chief among the regulatory T cells are "helper/inducer" cells. Typically identifiable by the T4 cell marker, helper T cells are essential for activating B cells and other T cells as well as natural killer cells and macrophages. Another subset of T cells acts to turn off or "suppress" these cells.

One of the first cytokines to be discovered was interferon. Produced by T cells and macrophages (as well as by cells outside the immune system), interferons are a family of proteins with antiviral properties. Interferon from immune cells, known as immune interferon or gamma interferon, activates macrophages. Two other cytokines, closely related to one another, are lymphotoxin (from lymphocytes) and tumor necrosis factor (from macrophages). Both kill tumor cells; tumor necrosis factor (TNF) also inhibits parasites and viruses.

Many cytokines are initially given descriptive names but, as their basic structure is identified, they are renamed as "interleukins"-messengers between leukocytes, or white cells. Interleukin-1, or IL-1, is a product of macrophages (and many other cells) that helps to activate B cells and T cells. IL-2, originally known as T cell growth factor, or TCGF, is produced by antigen-activated T cells and promotes the rapid growth or differentiation of mature T cells and B cells. IL-3 is a T-cell derived member of the family of protein mediators known as colony-stimulating factors (CSF); one of its many functions is to nurture the development of immature precursor cells into a variety of mature blood cells. IL-4, IL-5, and IL-6 help B cells grow and differentiate; IL-4 also affects T cells, macrophages, mast cells, and granulocytes.

A number of cytokines, obtained in quantity through recombinant DNA technology (Genetic Engineering), are now being used-alone, in combination, linked to toxins-in clinical trials for patients with cancers, blood disorders, and immunodeficiency diseases (including AIDS), as well as people receiving bone marrow transplants. Their versatility, however, makes it difficult to predict the full range of their effects.

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