Immune System



The immune system is a network of special cells, proteins, tissues, and organs that prevents the infection and growth of bacteria, viruses, and parasites in the body. It also prevents the uncontrolled growth of rogue cells or cancerous cells. In most cases, the immune system does a great job of keeping people healthy and preventing infections. But sometimes problems with the immune system can lead to illness and problems. At certain times, the immune system does not perform its functions adequately and infections occur. In other situations, the immune system is overactive and attacks normal cells of the body, leading to autoimmune disorders. In addition, the immune system may react to seemingly harmless particles or antigens such as pollen, causing allergies.

Description
The immune system is a network of cells, tissues, and organs that work together to defend the body against infection by bacteria, parasites, fungi and viruses. It also helps to prevent the development and growth of cancer cells. Normally, the immune system works in harmony with other systems in the body. There are times, however, when the immune system can "overreact" to an immune stimulus which can result in damage to normal, healthy tissues. Such is thought to be the case with diseases such as arthritis, lupus, and diabetes.

The immune system can also be weakened, either by infections such as HIV/AIDS or by cancer, or because of the use of drugs that suppress the immune system. Such drugs are used to stop the rejection of an organ transplant or to treat cancer. If the immune system is weakened, the condition is called immunosuppression or immune deficiency. In its weakened state, the immune system cannot defend the body and the result can be the development of opportunistic infections (infections that occur only with a weakened immune system) or cancer.

Role of in the Body
The immune system is the body's defense against infectious organisms and other invaders. Through a series of steps called the immune response, the immune system attacks organisms and substances that invade our body and cause disease. The immune system also monitors the body for cells that become damaged or that grow uncontrollably, such as cancer cells. It destroys these cells and removes them from the body. The immune system is made up of a network of cells, tissues, and organs that work together to protect the body.

How It Works
The immune system has two components: the innate system and the adaptive system. The innate component, though not specific for a particular microbe, is the first line of defense against infections. An example of innate immunity is the action of cilia in the lungs and respiratory tract; these are the fine "hairs" that sweep foreign material out of the lungs. The adaptive immune system is microbe-specific and is able to respond to almost any invader. It is amazingly complex. The adaptive immune system can recognize and remember millions of different invaders or antigens. It can produce antibody, other secretions (release of fluids), and cells to remove these invaders from the body. The innate and adaptive systems work together to provide complete immunity. They share many components, such as cells and molecules that activate both parts of the immune system.

Self and non-self
The key to a healthy immune system is its remarkable ability to distinguish between the body’s own cells, recognized as “self,” and foreign cells, or “non-self.” The body’s immune defenses normally coexist peacefully with cells that carry distinctive “self” marker molecules. But when immune defenders encounter foreign cells or organisms carrying markers that say “non-self,” they quickly launch an attack.

Anything that can trigger this immune response is called an antigen. An antigen can be almost anything that the body doesn't recognize: a microbe such as a virus, or a part of a microbe such as a protein molecule. Tissues or cells from another person (except an identical twin) also carry non-self markers and act as foreign antigens. This explains why tissue transplants may be rejected.

Antigens carry marker molecules that identify them as foreign. In abnormal situations, the immune system can mistake self for nonself and launch an attack against the body’s own cells or tissues. The result is called an autoimmune disease. Some forms of arthritis and diabetes are autoimmune diseases. In other cases, the immune system responds to a seemingly harmless foreign substance such as ragweed pollen. The result is allergy, and this kind of antigen is called an allergen.

Passive immunity
Passive immunity is "borrowed" from another source and lasts for a short time. For example, antibodies in a mother's breast milk provide an infant with temporary immunity to diseases to which the mother has been exposed. This can help protect the infant against infection during the early years of childhood.

Passive immunity can also be administered in the healthcare setting by giving immunoglobulins. For example, pregnant women who have a certain blood type (Rh negative) are sometimes given Rhogam, which is an immunoglobulin that protects the unborn child from attack by the mother's immune system should the child have an incompatible blood type. Similarly, many types of autoimmune diseases are also treated with different types of immunoglobulins.

Innate Immunity
Innate, or nonspecific, immunity is a type of general protection that humans and other animals are born with. Innate immunity protects the body against all antigens, and involved barriers that keep foreign materials from entering the body. These barriers form the first line of defense in the body's immune response. Examples of innate immunity include the following:


 * Skin
 * Mucous membranes (which trap bacteria and small particles)
 * Cough reflex
 * Enzymes in tears, saliva and skin oils
 * Stomach acid
 * Acidity and low ionic concentration of tears, saliva, and urine
 * Defensins (which are anti-microbial peptides secreted from epithelial surfaces)

Innate immunity also includes proteins released by the body, called innate humoral immunity. Examples include: the body's complement system and substances called interferon and interleukin-1 (which causes fever).

If an antigen is able to get through these natural barriers, it is attacked and destroyed by other parts of the immune system.

Adaptive immunity
A second kind of protection is called adaptive (or active) immunity. This type of immunity develops throughout our lives. Adaptive immunity involves lymphocytes called B cells and T cells and develops as children and adults are exposed to diseases or immunized against them through vaccination.

Components of the Immune System
The immune system is made up of the following components:

Organs
The organs of the immune system include the following:

Bone marrow
Bone marrow is the soft tissue in the hollow center of bones. It is where all blood cells, including the immune cells, grow.

Lymph nodes
Lymph nodes or glands, organized collections of lymphoid tissue where immune cells are found and where they interact with antigens.

Thymus
The thymus is an organ that lies behind the breastbone; lymphocytes known as T lymphocytes, or just T cells, mature there.

Spleen
The spleen is a flattened organ in the upper left of the abdomen. Like the lymph nodes, the spleen contains specialized compartments where immune cells gather and confront antigens.

Other lymphoid tissue
In addition to these organs, clumps of lymphoid tissue are found in many parts of the body, especially in the linings of the digestive tract and the airways and lungs&mdash;gateways to the body. These tissues include the tonsils, adenoids, and appendix.

Leukocytes
The cells that are part of this defense system are white blood cells, or leukocytes. Leukocytes are produced or stored in many locations throughout the body, including the thymus, spleen, and bone marrow. These organs are called the lymphoid organs. There are also clumps of lymphoid tissue throughout the body, primarily in the form of lymph nodes, that house the leukocytes.

Leukocytes circulate through the body between the organs and nodes by means of the lymphatic vessels. Leukocytes can also circulate through blood vessels. In this way, the immune system works in a coordinated manner to monitor the body for germs or substances that might cause problems.

The two basic types of leukocytes are:

Phagocytes
These are cells that engulf (phago means "to eat") and chew up invading microbes and foreigh particles. The different types of phagocytes include the following:

Monocytes are phagocytes that circulate in the blood. When monocytes migrate into tissues, they develop into macrophages. Specialized types of macrophages can be found in many organs, including the lungs, kidneys, brain, and liver.

Macrophages play many roles. As scavengers, they rid the body of worn-out cells and other debris. They also sweep up foreign particles like bacteria and viruses and display small bits of them as foreign antigen. This display activates matching lymphocytes which help rid the body of unwanted invaders. Macrophages also produce a variety of powerful chemical signals, known as monokines, which are central to the immune response.

Granulocytes are another type of phagocyte, and consist of neutrophils, basophils, and eosinophils. Neutrophils use prepackaged chemicals to break down the microbes they ingest. Eosinophils and basophils are related types of white blood cells that contain material that appears like granules under the microscope. These types of white bloods cells “degranulate” by spraying their chemicals onto harmful cells or microbes nearby.

Mast cells function much like basophils, except they are not found in the blood. Instead, they are found in the lungs, skin, tongue, and linings of the nose and intestinal tract, where they play a role in allergic reactions.

Related structures, called blood platelets, are actually cell fragments. Platelets also contain granules. In addition to promoting blood clotting and wound repair, platelets activate some immune defenses.

Dendritic cells are found in parts of lymphoid organs where T cells also exist. Like macrophages, dendritic cells in lymphoid tissues display antigens to T cells and help "turn on" T cells during an immune response. Dendritic cells get this name because they have branchlike extensions that can interlace to form a network.

Lymphocytes
Lymphocytes are small white blood cells that are part of the adaptive immune system. There are two kinds of lymphocytes: the B lymphocytes (B cells) and the T lymphocytes (T cells). Lymphocytes start out in the bone marrow and either stay there and mature into B cells, or they head to the thymus gland, where they mature into T cells.

When an antigen is detected, several types of cells, including antigen-presenting cells, work together to recognize and respond to it. These cells trigger the B lymphocytes to produce antibodies, specialized proteins that bind specific antigens. Antibodies and antigens fit together like a hand in glove.

Once the B lymphocytes have produced antibodies, they become memory cells. A few remain circulating in the blood, so that if the same antigen is presented to the immune system again, the antibodies are already there to do their job. That's why if someone gets sick with a certain disease, like chickenpox, that person typically doesn't get sick from it again&mdash;afterwards they are considered immune. This is also why we use vaccinations or immunizations to prevent getting certain diseases. The immunization introduces the body to the antigen in a way that doesn't make a person sick, but it does allow the body to produce antibodies that then protect that person from future attack by the disease-causing organism.

Antibodies
An antibody is made up of two heavy chains and two light chains, which together are called immunoglobulins. Antibodies also have a variable region, which differs from one antibody to the next, and allows an antibody to recognize its matching antigen. There are five types of immunoglobulin, (abbreviated as Ig):
 * IgG is a kind of antibody that works efficiently to coat microbes, speeding their uptake by other cells in the immune system.
 * IgM is very effective at killing bacteria.
 * IgA concentrates in body fluids—tears, saliva, and the secretions of the respiratory and digestive tracts—guarding the entrances to the body.
 * IgE protects against parasitic infections, and is also responsible for the symptoms of allergy.
 * IgD remains attached to B cells and plays a key role in initiating early B cell responses.

Antibodies can neutralize toxins (poisonous or damaging substances) produced by different organisms. They can also activate a group of proteins called complement that are also part of the immune system. Complement assists in killing bacteria, viruses, or infected cells.

Although antibodies can recognize an antigen and lock onto it, they are not capable of destroying it without help. That is the job of the T cells which contribute to immune defenses in two major ways: some direct and regulate immune responses, whereas others directly attack infected or cancerous cells. There are actually T cells that are called "killer T cells." The T cells are part of the system that destroys antigens that have been tagged by antibodies, or cells that have been infected or somehow changed. T cells are also involved in helping signal other cells (like phagocytes) to do their jobs.

Unlike B cells, T cells do not recognize free-floating antigens. Rather, their surfaces contain specialized antibody-like receptors that see fragments of antigens on the surfaces of infected or cancerous cells.

Helper T cells, or Th cells, coordinate immune responses by communicating with other cells. Some stimulate nearby B cells to produce antibodies, others call in phagocytes, and still others activate other T cells.

Cytotoxic T lymphocytes (CTLs)—also called killer T cells—perform a different function. These cells directly attack other cells carrying certain foreign or abnormal molecules on their surfaces. CTLs are especially useful for attacking viruses because viruses often hide from other parts of the immune system while they grow inside infected cells. CTLs recognize small fragments of these viruses peeking out from the cell membrane and launch an attack to kill the infected cell.

Cells of the immune system communicate with one another by releasing and responding to chemical messengers called cytokines. These proteins are secreted by immune cells and act on other cells to coordinate appropriate immune responses. Cytokines include a diverse assortment of compounds called interleukins, interferons, and growth factors.

Complement
The complement system is made up of about 25 proteins that work together to assist, or “complement,” the action of antibodies in destroying invaders. Complement also helps to rid the body of antibody-coated antigens (antigen-antibody complexes). Complement proteins, which cause blood vessels to become dilated and then leaky, contribute to the redness, warmth, swelling, pain, and loss of function that characterize an inflammatory response.

Complement proteins circulate in the blood in an inactive form. When the first protein in the complement series is activated—typically by antibody that has locked onto an antigen—it sets in motion a domino effect. Each component takes its turn in a precise chain of steps known as the complement cascade. The end products are molecular cylinders that are inserted into—and that punch holes in—the cell walls that surround the invading bacteria. This causes certain fluids and molecules to flow into the bacterium and others to flow out. The end result is that the bacterial cell swells, bursts, and dies. Other components of the complement system make bacteria more susceptible to being eaten by phagocytes, or beckon other immune cells to the area.

Vaccines
An immune response can be sparked not only by infection but also by immunization with vaccines. Some vaccines contain microorganisms, or parts of microorganisms, that have been treated so they can provoke an immune response but not full-blown disease. Vaccines consist of killed or modified microbes, components of microbes, or microbial DNA that trick the body into thinking an infection has occurred.

A vaccinated person’s immune system attacks the harmless vaccine, which prepares the body for future invasions against the kind of microbe the vaccine contained. In this way, the person becomes immunized against the microbe. Vaccination remains one of the best ways to prevent infectious diseases, and vaccines have an excellent safety record. Previously devastating diseases such as smallpox, polio, and whooping cough have been greatly controlled or eliminated through worldwide vaccination programs.

Some vaccines contain a weakened form of a live virus. The yellow fever vaccine and the oral polio vaccine are examples of this type of vaccine. As a general rule, people who have a weakened immune system should not receive a vaccine that contains live virus. Vaccines containing killed virus can be used instead. There are other conditions where a doctor may decide not to give a vaccine.

Disorders of the
Disorders of the immune system can be broken down into four main categories:


 * Immunodeficiency disorders (primary or acquired)
 * Autoimmune disorders (in which the body's own immune system attacks its own tissue as foreign matter)
 * Allergic disorders (in which the immune system overreacts in response to an antigen)
 * Cancers of the immune system

Autoimmune disorders
Autoimmunity is a condition where the immune system mistakenly recognizes host tissue or cells as foreign. Because of this false recognition, the immune system reacts against the host components. There are a variety of autoimmune disorders. An autoimmune disease can be very specific, involving a single organ. Three examples are Crohn's disease (where the intestinal tract is the target), multiple sclerosis (where tissues of the brain are the target), and diabetes mellitus Type I (where the insulin-producing cells of the pancreas are the target).

Other autoimmune disorders are more general, and involve multiple sites in the body. One example is rheumatoid arthritis.

Allergy
These types of disorders result when the immune system overreacts or reacts inappropriately (eg., allergies, systemic lupus erythematosus)

Immune deficiencies
These types of disorders are the result of diminished immune function [eg.,AIDS, severe combined immunodeficiency (SCID)]

Related Professions
An immunologist is typically a medical professional who has received an MD or PhD with special emphasis and.training in the immune system and immune disorders.

Clinical Trials
A list of open clinical research trials studying the immune system is available here.

Immune System and Cancer
When normal cells turn into cancer cells, some of the antigens on their surface change. These cells, like many body cells, constantly shed bits of protein from their surface into the circulatory system. Often, tumor antigens are among the shed proteins.

These shed antigens prompt action from immune defenders, including cytotoxic T cells, natural killer cells, and macrophages. According to one theory, patrolling cells of the immune system provide continuous body-wide surveillance, catching and eliminating cells that undergo malignant transformation. Tumors develop when this immune surveillance breaks down or is overwhelmed.

Research
Scientists are now able to mass-produce immune cell secretions, both antibodies and lymphokines, as well as specialized immune cells. The ready supply of these materials not only has revolutionized the study of the immune system itself but also has had an enormous impact on medicine, agriculture, and industry.

Monoclonal antibodies are identical antibodies made by the many clones of a single B cell. Monoclonal antibody technology makes it possible to mass produce specific antibodies to order. Because of their unique specificity for different antigens, monoclonal antibodies are promising treatments for a range of diseases. Researchers make monoclonal antibodies by injecting a mouse with a target antigen and then fusing B cells from the mouse with other long-lived cells. The resulting hybrid cell becomes a type of antibody factory, turning out identical copies of antibody molecules specific for the target antigen.

Mouse antibodies are “foreign” to people, however, and might trigger an immune response when injected into a human. Therefore, researchers have developed “humanized” monoclonal antibodies. To construct these molecules, scientists take the antigen-binding portion of a mouse antibody and attach it to a human antibody scaffolding, greatly reducing the foreign portion of the molecule.

Because they recognize very specific molecules, monoclonal antibodies are used in diagnostic tests to identify invading pathogens or changes in the body’s proteins. In medicine, monoclonal antibodies can attach to cancer cells, blocking the chemical growth signals that cause the cells to divide out of control. In other cases, monoclonal antibodies can carry potent toxins into certain cells, killing the dangerous cells while leaving their neighbors untouched.

Gene Therapy
Genetic engineering also holds promise for gene therapy—replacing altered or missing genes or adding helpful genes. One disease in which gene therapy has been successful is SCID, or severe combined immune deficiency disease.

SCID is a rare genetic disease that disables a person’s immune system and leaves the person unable to fight off infections. It is caused by mutations in one of several genes that code for important components of the immune system. Until recently, the most effective treatment for SCID was transplantation of blood-forming stem cells from the bone marrow of a healthy person who is closely related to the patient. However, doctors have also been able to treat SCID by giving the patient a genetically engineered version of the missing gene.

Using gene therapy to treat SCID is generally accomplished by taking blood-forming cells from a person’s own bone marrow, introducing into the cells a genetically changed virus that carries the corrective gene, and growing the modified cells outside the person’s body. After the genetically changed bone marrow cells begin to produce the enzyme or other protein that was missing, the modified blood-forming marrow cells can be injected back into the person. Once back inside the body, the genetically modified cells can produce the missing immune system component and begin to restore the person’s ability to fight off infections.

Cancer is another target for gene therapy. In pioneering experiments, scientists are removing cancer-fighting lymphocytes from the cancer patient’s tumor, inserting a gene that boosts the lymphocytes’ ability to make quantities of a natural anticancer product, then growing the restructured cells in quantity in the laboratory. These cells are injected back into the person, where they can seek out the tumor and deliver large doses of the anticancer chemical.

Although scientists have learned much about the immune system, they continue to study how the body launches attacks that destroy invading microbes, infected cells, and tumors while ignoring healthy tissues. New technologies for identifying individual immune cells are now allowing scientists to determine quickly which targets are triggering an immune response. Improvements in microscopy are permitting the first-ever observations of living B cells, T cells, and other cells as they interact within lymph nodes and other body tissues.

In addition, scientists are rapidly unraveling the genetic blueprints that direct the human immune response, as well as those that dictate the biology of bacteria, viruses, and parasites. The combination of new technology and expanded genetic information will no doubt reveal even more about how the body protects itself from disease.