Immune System.

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Immune System.
I

INTRODUCTION

Immune System, group of cells, molecules, and organs that act together to defend the body against foreign invaders that may cause disease, such as bacteria, viruses,
and fungi. The health of the body is dependent on the immune system's ability to recognize and then repel or destroy these invaders.

II

IMMUNITY: INNATE AND ADAPTIVE

Most animals have systems that resist disease. The disease resistance provided by these systems is called immunity. There are two types of immunity: innate and
adaptive. Innate, or nonspecific, immunity is the body's first, generalized line of defense against all invaders. Innate immunity is furnished by barriers such as skin,
tears, mucus, and saliva, as well as by the rapid inflammation of tissues that takes place shortly after injury or infection. These innate immune mechanisms hinder the
entrance and spread of disease but can rarely prevent disease completely.
If an invader gets past this first line of defense, the cells, molecules, and organs of the immune system develop specifically tailored defenses against the invader. The
immune system can call upon these defenses whenever this particular invader attacks again in the future. These specifically adapted defenses are known as adaptive,
or specific, immunity.
Adaptive immunity has four distinguishing properties: First, it responds only after the invader is present. Second, it is specific, tailoring each response to act only on a
specific type of invader. Third, it displays memory, responding better after the first exposure to an invader, even if the second exposure is years later. Fourth, it does
not usually attack normal body components, only those substances it recognizes as nonself.
Adaptive immune responses are actually reactions of the immune system to structures on the surface of the invading organism called antigens. There are two types of
adaptive immune responses: humoral and cell mediated. During humoral immune responses, proteins called antibodies, which can stick to and destroy antigens, appear
in the blood and other body fluids. Humoral immune responses resist invaders that act outside of cells, such as bacteria and toxins (poisonous substances produced by
living organisms). Humoral immune responses can also prevent viruses from entering cells.
During cell-mediated immune responses, cells that can destroy other cells become active. Their destructive activity is limited to cells that are either infected with, or
producing, a specific antigen. Cell-mediated immune responses resist invaders that reproduce within the body cells, such as viruses. Cell-mediated responses may also
destroy cells making mutated (changed) forms of normal molecules, as in some cancers.

III

COMPONENTS OF THE IMMUNE SYSTEM

The ability of the immune system to mount a response to disease is dependent on many complex interactions between the components of the immune system and the
antigens on the invading pathogens, or disease-causing agents.

A

Macrophages

White blood cells are the mainstay of the immune system. Some white blood cells, known as macrophages, play a function in innate immunity by surrounding, ingesting,
and destroying invading bacteria and other foreign organisms in a process called phagocytosis (literally, "cell eating"), which is part of the inflammatory reaction.
Macrophages also play an important role in adaptive immunity in that they attach to invading antigens and deliver them to be destroyed by other components of the
adaptive immune system.

B

Lymphocytes

Lymphocytes are specialized white blood cells whose function is to identify and destroy invading antigens. All lymphocytes begin as "stem cells" in the bone marrow, the
soft tissue that fills most bone cavities, but they mature in two different places. Some lymphocytes mature in the bone marrow and are called B lymphocytes. B
lymphocytes, or B cells, make antibodies, which circulate through the blood and other body fluids, binding to antigens and helping to destroy them in humoral immune
responses.
Other lymphocytes, called T lymphocytes, or T cells, mature in the thymus, a small glandular organ located behind the breastbone. Some T lymphocytes, called
cytotoxic (cell-poisoning) or killer T lymphocytes, generate cell-mediated immune responses, directly destroying cells that have specific antigens on their surface that
are recognized by the killer T cells. Helper T lymphocytes, a second kind of T lymphocyte, regulate the immune system by controlling the strength and quality of all
immune responses.
Most contact between antigens and lymphocytes occurs in the lymphoid organs--the lymph nodes, spleen, and tonsils, as well as specialized areas of the intestine and
lungs (see Lymphatic System). Mature lymphocytes constantly travel through the blood to the lymphoid organs and then back to the blood again. This recirculation
ensures that the body is continuously monitored for invading substances.

C

Antigen Receptors

One of the characteristics of adaptive immunity is that it is specific: Each response is tailored to a specific type of invading antigen. Each lymphocyte, as it matures,
makes an antigen receptor--that is, a specific structure on its surface that can bind with a matching structure on the antigen like a lock and key. Although lymphocytes
can make billions of different kinds of antigen receptors, each individual lymphocyte makes only one kind. When an antigen enters the body, it activates only the
lymphocytes whose receptors match up with it.

D

Antigen-Presenting Cells

When an antigen enters a body cell, certain transport molecules within the cell attach themselves to the antigen and transport it to the surface of the cell, where they
"present" the antigen to T lymphocytes. These transport molecules are made by a group of genes called the major histocompatibility complex (MHC) and are therefore
known as MHC molecules. Some MHC molecules, called class I MHC molecules, present antigens to killer T cells; other MHC molecules, called class II MHC molecules,
present antigens to helper T cells.

IV

HUMORAL IMMUNE RESPONSE

The humoral immune response involves a complex series of events after antigens enter the body. First, macrophages take up some of the antigen and attach it to class
II MHC molecules, which then present the antigen to T helper cells. The T helper cells bind the presented antigen, which stimulates the T helper cells to divide and
secrete stimulatory molecules called interleukins. The interleukins in turn activate any B lymphocytes that have also bound the antigen. The activated B cells then divide
and secrete antibodies. Finally, the secreted antibodies bind the antigen and help destroy it.

A

Antibodies

Antibodies are Y-shaped proteins called immunoglobulins (Ig) and are made only by B cells. The antibody binds to the antigen at the ends of the arms of the Y. The area
at the base of the Y determines how the antibody will destroy the antigen. This area is used to categorize antibodies into five main classes: IgM, IgG, IgA, IgD, and IgE.
During the humoral immune response, IgM is the first class of antibody made. After several days, other classes appear. Exactly which other Ig classes a B cell makes
depends on the kind of interleukins it receives from the T helper cells.
Antibodies can sometimes stop an antigen's disease-causing activities simply by neutralization--that is, by binding the antigen and preventing it from interfering with
the cell's normal activities. For example, the toxin made by tetanus bacteria binds to nerve cells and interferes with their control of muscles. Antibodies against tetanus
toxin stick to the toxin and cover the part of it that binds to nerve cells, thereby preventing serious disease. All classes of antibodies can neutralize antigens.
Antibodies also help destroy antigens by preparing them for ingestion by macrophages in a process called opsonization. In opsonization, antibodies coat the surface of
antigens. Since macrophages have receptors that stick to the base of the antibody's Y structure, antigens coated with antibodies are more likely to stick to the
macrophages and be ingested. Opsonization is especially important in helping the body resist bacterial diseases.
Finally, IgM and IgG antibodies can trigger the complement system, a group of proteins that cause cells to disintegrate by cutting holes in the cell membrane.
Complement is important in resisting bacteria that are hard to destroy in other ways. For example, some of the bacteria that cause pneumonia have a slimy coating,
making it hard for macrophages to ingest and eliminate them. However, if IgM and IgG antibodies bind to the pneumonia bacteria and activate the complement system,
it is able to cut holes in the bacteria to destroy them.
Although the IgM and IgG classes of antibodies work best in the circulatory system, IgA can exit the bloodstream and appear in other body fluids. IgA is thus important
in preventing infection at mucosal surfaces, such as the intestine and the lung. Since these are the sites where most infectious agents enter, IgA is particularly
important in resistance to many diseases. IgA is also found in mother's milk and may help nursing newborns resist disease.

V

CELL-MEDIATED IMMUNE RESPONSE

As with the humoral immune response, the cell-mediated immune response involves a complex series of events after antigens enter the body. Helper T cells are
required, so some of the antigen must be taken up by macrophages and presented to helper T cells. The helper T cells bind the presented antigen and thereby become
activated to divide and secrete interleukins. The interleukins in turn activate any killer T cells that have already bound antigen attached to class I MHC molecules on
infected cells. The activated killer T cells can then kill any cells displaying antigen attached to class I MHC molecules, effectively eliminating any cells infected with the
antigen.

VI

IMMUNIZATION

When the body is first exposed to an antigen, several days pass before the adaptive immune response becomes active. Immune activity then rises, levels off, and falls.
During following exposures to the same antigen, the immune system responds much more quickly and reaches higher levels. Because the first, or primary, immune
response is slow, it cannot prevent disease, although it may help in recovery. In contrast, subsequent, or secondary, immune responses usually can prevent disease
because the pathogen is detected, attacked, and destroyed before symptoms appear. This complete resistance to disease is called immunity and may be achieved
through either active or passive immunization.

A

Active Immunization

Active immunization occurs when a person's own immune system is activated and generates a primary immune response. Active immunization can be triggered in two
ways, either by natural immunization or by vaccination.
In natural immunization, the body contracts a disease and recovers. Because a primary immune response occurs during the illness, the immune system will mount a
disease-preventing secondary response every time it is subsequently exposed to the disease. Natural immunization is developed during childhood diseases, such as
chicken pox. After having had the disease once, a person is no longer susceptible to it.
Vaccination is intentional immunization against a particular disease by the use of vaccines, substances that are structurally similar to the actual disease-producing
agents but that do not produce disease themselves. Most vaccines take one of two forms. The first type of vaccine, such as the vaccines for tetanus and whooping
cough, contains chemically killed bacteria or other pathogenic organisms. The other type, such as the oral polio vaccine, contains weakened forms of living organisms
that have been genetically selected so they do not produce disease.

B

Passive Immunization

Another way to provide immunity is by means of passive immunization. Passive immunization does not engage the person's own immune system. Instead, the individual
receives antibodies that were created in another person or animal. Such antibodies can be lifesaving when a disease progresses too rapidly for natural immunization to
occur. For example, if a person who has not been immunized against tetanus bacteria is exposed to tetanus, the toxin produced by these bacteria would reach a deadly
level before a primary immune response could begin. Administering antibodies against tetanus toxin quickly neutralizes the toxin and prevents death.
Passive immunization has two drawbacks: First, the person does not mount an active immune response, so the immunizing effect is temporary and the person is not
immune after recovery. Second, if passive immunization is used repeatedly, it occasionally produces side effects.

VII

IMMUNE SYSTEM DISORDERS

Disorders of the immune system can range from the less serious, such as mild allergy, to the life threatening, such as more serious allergy, transplant rejection,
immune deficiencies, and autoimmune diseases.

A

Allergy

Allergy, sometimes called hypersensitivity, is caused by immune responses to some antigens. Antigens that provoke an allergic response are known as allergens. The
two major categories of allergic reaction, rapid and delayed, correspond to the two major types of immune responses.
Rapid allergic reactions, such as those to bee venom, pollen or pets, are caused by humoral immune mechanisms. These immediate hypersensitivity reactions result
from the production of IgE antibodies when a person is first exposed to an allergen. The IgE antibodies become attached to mast cells--white blood cells containing
histamine, the chemical that causes the familiar allergic symptoms of runny nose, watery eyes, and sneezing. Mast cells are particularly abundant in the lungs and
intestine. If the antigen-binding sites of mast cells become filled with an allergen, the mast cells release histamine.
Allergic reactions that are slow in onset (known as delayed-type hypersensitivity, or DTH), such as those to poison ivy or poison oak, are cell mediated. Extreme
examples of DTH occur when macrophages cannot easily destroy invading substances. As a result, T cells are activated, leading to inflammation of the body tissue. This
inflammation continues for as long as the T cells are activated. The bacterium that causes tuberculosis also falls into this category because this bacterium is covered with
a waxy coat that macrophages cannot destroy. The resulting DTH leads to the lung and liver damage associated with tuberculosis.

B

Transplant Rejection

The immune system recognizes and attacks anything different from the substances normally present within an individual, even substances that are only slightly
different, such as transplanted tissues and organs (see Transplantation, Medical).
When an organ is transplanted, the MHC of the donor organ is recognized as foreign and attacked by the recipient's immune system. To minimize the chances of
transplant rejection, physicians seek transplant donors who share as many MHC genes as possible with the transplant recipient. Even then, most transplant recipients
are given drugs to suppress their immune response and prevent rejection of the transplant.
If the transplanted tissue contains T lymphocytes from the donor, as in bone marrow transplants, these donor T lymphocytes may recognize the recipient's tissues as
foreign and attack them. Physicians can reduce or prevent this potentially fatal graft-versus-host (GVH) reaction by removing all mature T lymphocytes from the organ
or tissue before performing the transplant.

C

Immune Deficiency

Deficiencies in immune function may be either inherited or acquired. Inherited immune deficiencies usually reflect the failure of a gene important to the generation or
function of immune system components.
Some inherited diseases damage a person's innate immunity by making macrophages incapable of ingesting or breaking down invading organisms. Individuals affected
by these diseases are especially susceptible to opportunistic infections--that is, infections by normally harmless organisms that can flourish in a person whose immune
system has been weakened.
DiGeorge syndrome is an inherited immune disorder in which a person has no thymus and, therefore, cannot produce mature T lymphocytes. People with this disorder
can mount only limited humoral immune responses, and their cell-mediated immune responses are severely limited.
The most extreme example of a hereditary immune deficiency is severe combined immunodeficiency (SCID). Individuals with this disease completely lack both T and B
lymphocytes and thus have no adaptive immune responses. People with SCID must live in a completely sterile environment, or else they will quickly die from infections.
Acquired immune deficiencies can be caused by infections and also other agents. For example, radiation therapy (see Radiology) and some kinds of drugs used in
treating disease reduce lymphocyte production, resulting in damaged immune function. People undergoing such therapies must be carefully monitored for lowered
immune function and susceptibility to infections. Environmental and lifestyle factors, such as poor nutrition or stress, can also affect the immune system's general
status.
An infectious agent resulting in fatal immune deficiency is the human immunodeficiency virus (HIV). This virus causes acquired immunodeficiency syndrome (AIDS) by
infecting and eventually destroying helper T cells. Because helper T cells regulate all immune responses, their loss results in an inability to make adaptive immune
responses. This complete lack of immune function makes individuals with AIDS highly susceptible to all infectious agents.

D

Autoimmune Diseases

Autoimmunity is the immune response of the body turned against its own cells and tissues. Autoimmune diseases may involve either cell-mediated responses, humoral
responses, or both. For example, in Type 1 diabetes, the body makes an immune response against its insulin-producing cells and destroys them, with the result that the
body cannot use sugars. In myasthenia gravis, the immune system makes antibodies against the normal molecules that control neuromuscular activity, causing
weakness and paralysis. In rheumatic fever, the immune system makes antibodies that bind to the heart's valves, leading to permanent heart damage. In systemic
lupus erythematosus, commonly known as lupus, the body makes antibodies against many different body tissues, resulting in widespread symptoms.
The mechanisms of autoimmune diseases are poorly understood, and thus the basis for autoimmunity is unclear. Much research focuses on trying to understand these
mechanisms and should eventually result in cures.

Contributed By:
Michael P. Cancro
Microsoft ® Encarta ® 2009. © 1993-2008 Microsoft Corporation. All rights reserved.