What is the immune system?

Structure and Functions

The immune system is capable of recognizing and identifying many different substances foreign to the human body. To function properly, this system must receive, interpret, and transmit large amounts of information about invaders from outside or within the body. These constant and ever-changing threats to the body must be met and destroyed by one complex system—namely, the human immune system. Many organs and parts of the body play a major role in maintaining resistance; some have more important roles than others, but all parts must work in unison. The circulatory and lymphatic systems, along with specific organs, are of primary importance in the overall workings of the immune system.

Blood. Besides the outer protective layer of the skin and mucous membranes, the first line of defense in the immune system includes the blood in the circulatory system. About 50 percent of human blood is made up of a fluid called plasma, which contains water, proteins, carbohydrates, vitamins, hormones, and cellular waste. The other half of blood is composed of white cells, red cells, and platelets. The red blood cells, called erythrocytes, are responsible for moving oxygen from the lungs to the other parts of the body. The special platelet cells, called thrombocytes, enable the blood to form clots, thus preventing severe bleeding. An unborn child produces red and white blood cells in the spleen and liver, while a newborn makes blood in the center of bones, called the marrow. After maturity, all red and most white blood cells are produced in the bone marrow. Although the red cells and platelets are vital, it is the white cells that play a major role in
the immune system.

In a broad sense, white blood cells surround and engulf foreign matter and adjacent dying cells in a process called phagocytosis. The function is possible since the white blood cells can move, unlike red corpuscles, by pushing their bodies out and pulling forward. Red corpuscles move because of the flow of the blood within the circulatory system. White blood cells move in the lymph vessels, where they work to defend the body against disease, but are also transported through the blood. Bacteria and other foreign material can remain alive within a white corpuscle, but sometimes the corpuscle dies from the toxins produced by the bacteria. The resulting formation of pus is actually an accumulation of dead white blood cells. At other times, the white corpuscles win and the foreign matter is destroyed.

Three major types of white blood cells, known collectively as leukocytes, are involved in immune responses. All three—granulocytes, monocytes, and lymphocytes—arise from areas in either bone marrow, the spleen, or the liver.

The granulocytes, each of which is about twice the size of a red blood cell, originate from red bone marrow and live only about twelve hours. Under the classification of granulocytes, distinct cells have different structures, sizes, and shapes. These specialized granulocytes include the neutrophils, eosinophils, and basophils. None of these cells has a specific memory for future immune responses. The neutrophil
granulocyte eats and digests small foreign matter with the help of special enzymes. Between 40 and 75 percent of the white blood cells in the human body are neutrophils. When these highly mobile neutrophil cells arrive at an injury site, they burst, releasing their enzymes and melting away the surrounding tissues. Eosinophils are similar to neutrophils but seem to be specialized in fighting infection caused by parasites, because of the seven toxic proteins that they use to fight. They are also effective against fungal, bacterial, viral, or protozoan
infections. Basophils, which are smaller in size, move from the bone marrow through the body and act as a control by preventing overreactions during an immune response. Basophils prevent coagulation, but they cannot destroy foreign matter. These cells account for less than 1 percent of the white blood cells found in the blood.

The second group of leukocytes includes the monocytes, the largest cells found in the blood. Monocytes are two to three times as large as red cells, yet they are not very numerous, making up 3 to 9 percent of all the leukocytes in the blood. After only a few days in the blood, they move to areas between tissues. Over the course of months or years, the monocytes enlarge ten times in size in order to specialize in phagocytosis. After this growth, they are called macrophages. They are also referred to as terminal cells since they cannot divide, and thus do not reproduce.

The third type of leukocyte, and the most sophisticated of the white blood cells, are called lymphocytes because they come from the lymph system as well as bone marrow. The T lymphocytes, which are primarily responsible for immunity, can change into helper, killer, and suppressor cells. Besides being able to recognize foreign matter precisely, they can live freely in the blood, grow larger and divide, and then change back to their original form after working against the invader. Lymphocytes circulate throughout the body, moving from the bloodstream through the lymph fluid and back into the blood. The two major types of lymphocytes are T lymphocytes (also called T cells) and B lymphocytes (also called B cells). Both T and B cells can recognize foreign matter and hook onto it. Some of these special “memory” cells remain in the body for life, preventing a specific invader from causing illness when it is encountered again in the future. These specialized cells must have a way to travel through the body; one of these transport systems is the lymphatic system.

The lymphatic system. This system is a closed network of vessels that help in circulating fluids from the body and returning them to the bloodstream. The
lymphatic system also defends against disease-causing foreign materials, known as antigens. The smallest components of the lymph system are the lymphatic capillaries that run parallel to the blood capillaries. The fluid inside these capillaries, which has come across the thin wall membrane from tissues all across the body, is called lymph. These capillaries merge into larger lymphatic vessels, which then merge into a type of collecting area called a lymph node. The lymph fluid is drained into trunks that join one of two collecting ducts. The larger left thoracic duct collects lymph from the lower part of the abdomen and the legs, and from the left side of the upper body before emptying into a vein near the neck and shoulder. The right lymphatic duct does the same for the right side of the upper body. After leaving the collecting ducts, the lymph fluid becomes part of the blood plasma in the veins and returns to the right atrium of the heart. Lymph does not flow like blood in veins and arteries; instead, it is controlled by muscular activity.

The spleen. This largest lymphatic organ is located in the upper left part of the abdominal cavity, behind the stomach and under the diaphragm. The hollow spaces within the spleen are filled with blood, making it soft and elastic. The white blood cells in the lining of these hollow cavities engulf and destroy foreign materials, as well as damaged red blood cells that pass through the spleen.

The thymus. This gland is located between the lungs and above the heart, just behind the upper part of the breastbone. It contains large numbers of white cells; some are inactive, but others develop and leave the
thymus to become functional in the immune system.

The liver. Located in the upper right part of the abdominal cavity below the diaphragm, the liver is well protected by the ribs. Since it is the largest gland in the body, it plays a major role in metabolism while also aiding the body’s ability to clot blood. In addition, various liver cells, called macrophages, help in destroying damaged red blood cells. The liver’s connection to the immune system is its ability to also destroy foreign substances through phagocytosis.

Bone marrow. Marrow is located in the center of bones. It can be divided into two types, red or yellow marrow. It is the red marrow that aids in the formation of white and red blood cells. The yellow marrow stores fat and is not involved in producing blood cells. Some white blood cells come from bone marrow cells. They are released into the blood and are carried to the thymus gland, where they undergo special processing that changes them into T lymphocytes (the letter T shows that they came from the thymus gland). The other lymphocytes that do not reach the thymus after leaving the bone marrow are named B lymphocytes (B because they came from bone marrow). These B lymphocytes are abundant in lymph nodes, the spleen, bone marrow, secretory glands, intestinal lining, and reticuloendothelial tissue.

The Responses of the Immune System

Failures of the immune system can lead to devastating diseases, either because the immune system attacks itself or because it fails to defend against outside foreign antigen matter. An antigen can be any substance that stimulates the body to fight, ranging from a bacterial infection to the virus that causes acquired immunodeficiency syndrome (AIDS).

When the body fights against an antigen, the immune system can produce two types of response, either a cellular immune response or a humoral immune response. The cellular response involves specific types of cells that recognize, attack, and destroy the invading pathogen or antigen. It is the primary response against most viruses, many fungi, parasitic organisms and some bacteria (for example, mycobacteria), and against transplanted tissues. The humoral immune response, which consists of complement and antibodies, is the body’s main defense against most other bacteria. The two systems work together, however, communicating by complex chemical mediators.

Another way of looking at how the body fights to keep itself healthy is to separate the immune responses into either primary or secondary responses. The second time that a given antigen enters the body, the immune system attacks with what is called the secondary immune response stored in special immune memories, making it faster and more extensive than the primary response that occurred when the antigen was first encountered. This immune memory must be built for each antigen before the body becomes immune to the wide variety of diseases and conditions to which one is exposed on a daily basis.

The body begins to build this memory prior to birth by making an inventory of all the molecules within the body. Foreign substances not in this memory are considered to be antigens, which will activate an immune response. When an antigen is first encountered, the primary response occurs, producing lymphocytes that are sensitized to the invader. Many types of lymphocytes can respond in order to create the appropriate antibody molecules, which are then released into the lymph and transported to the blood. This process may last several weeks. During this primary immune response, the B cells and T cells serve as memory cells. Because a memory for the antigen has been stored, if this antigen is encountered in the future the memory cells can react more quickly and effectively. In this secondary immune response, the antibodies are ready to react by attaching themselves to the surfaces of the antigens. There must be a specific type of antibody produced for every type of antigen. These new antibodies may survive only a few months, but the memory cells live much longer.

There are four main ways that an antibody can bind to an antigen. The antibody can pull together clusters of invading organisms to prevent the antigens from spreading. Another possibility is for this special component of the blood to punch a hole in the invader and destroy it. The antibody can also combine with the antigen, which makes it easier to destroy. In the case of a virus or a toxin, the antibody can neutralize the harmful activity by covering the outside of the antigen. With so many ways for an antibody to attach to an antigen, it is equally important for the antibody memory to be established. It is this special memory that leads to future immunity.

These memory cells are responsible for the four different types of immunity, two of which are acquired actively and two of which are acquired passively. The first type is naturally acquired active immunity, which results after the body is exposed to a live pathogen and develops the disease. The second type is artificially acquired active immunity, such as that gained after a vaccination. The immune response is triggered after an injection of weakened or dead pathogens is received, but the body does not suffer the severe symptoms of the disease. An example would be a smallpox vaccination. The third type of immunity is artificially acquired passive immunity, gained through an injection of prepared antibodies. This method is considered passive since the antibodies, called gamma globulin, were made by another person. This type of immunity usually does not last more than a few weeks, and the person will be susceptible to that pathogen in the future. Naturally acquired passive immunity occurs when the antibodies pass to the fetus from the mother, but it includes only
those antibodies available in the blood of the mother. This process gives an infant certain short-term immunities for the first year of life.

These types of immunity are usually desirable, but there are occasions when an immune response is not wanted, such as after an organ transplant. When tissue or organs are transplanted from one person to another, the body may reject the foreign tissue, triggering an immune response and possibly destroying the new organ. Consequently, attempts are made to match the tissue between recipient and donor. In an effort to halt the immune response, immunosuppressive drugs are given to interfere with the recipient’s ability to form antibodies, and drugs can be administered to destroy the lymphocytes that produce these antibodies. Unfortunately, the recipient is often left unprotected against infections, since the immune system is not functioning normally.

Perspective and Prospects

In the same way that the discovery of penicillin shocked the world,
immunology has created endless possibilities in medicine. When surgeons found that they could transplant an organ from one person to another, the interest in immunology exploded.

This field of medicine has discovered that the immune system’s power and effectiveness can be lessened because of several factors. Improper diet, stress, disease, and excessive physical activity levels can depress the immune system. Other factors that can modify immunity include age, genetics, and metabolic and environmental factors. The anatomical, physiological, and microbial factors are shown in the susceptibility of the young and the very old to infections. For the young, the system is immature, while the aged have suffered a lifetime of assaults from pathogens. The impact of psychological stress is difficult to measure, yet it holds the potential for negatively affecting the immune system.

Before immunology can be fully understood, more knowledge must be gained about how antibodies are made and how they develop memories. Lymphocytes must be examined to discover what role they play in the immune response. Studies must look at not only the whole picture of the immune system but also its smaller parts—the organs and how each participates. Such studies could lead to better success in transplanting these organs. Unanswered questions remain about how the immune system relates to other body systems. The relationships among the brain and nervous system, hormones, and the respiratory system leave many areas ripe for further study.

Recent research has identified the significant importance of Class I major histocompatibility proteins (I-MHCPs) in the cellular immune system. When disease-associated proteins occur in a cell, they are broken into pieces by the cell’s proteolytic machinery. Cell proteins become attached to antigen fragments and transport them to the surface of the cell, where they are “presented” to the body’s defense mechanisms. I-MHCPs are these transport molecules. The I-MHCPs holding an antigen fragment can attach to certain immature T cells. Once such a T cell and I-MHCP-antigen complex hook up, the T cell reproduces many times. This important link between the cellular immune system and I-MHCPs has been shown in recent times by the epidemic of diseases like AIDS, which kills T cells. Class II MHCPs (II-MHCPs) interact similarly in antibody production by the humoral immune system. Understanding of the genes used in production of the I-MHCPs and the II-MHCPs has led to great hope for methods to control their production, possibilities for eventual cure of AIDS, emerging
cancer treatments, and better understanding of the production of antibodies.

Additional information is needed on defects in the system, as are explanations for its dysfunctions. With greater knowledge of immunology, it may be possible to conquer AIDS, allergies, and asthma and to develop birth control methods based on the immune response. Doctors may be able to cure cancer, diabetes, herpes, infertility, multiple sclerosis, and rheumatoid arthritis. The possibilities are endless and could also include perfecting transplants of organs and skin grafts and preventing birth defects and even obesity. Through human gene therapy, those at risk for genetic disorders could be diagnosed and those with existing genetic conditions could be treated. Genetically engineered drugs and gene replacement therapy could relieve the stress on the human immune system. Until these methods become feasible, however, individuals must protect the natural immunity supplied by their bodies.

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