Overview of the Immune System

The first line of defense against invaders is mechanical or physical barriers:

• The skin

• The cornea of the eyes

• Membranes lining the respiratory, digestive, urinary, and reproductive tracts

As long as these barriers remain unbroken, many invaders cannot enter the body. If a barrier is broken—for example, if extensive burns (or even minor cuts) damage the skin—the risk of infection is increased.

In addition, the barriers are defended by secretions containing proteins called enzymes that can destroy bacteria. Examples are sweat, tears in the eyes, mucus in the respiratory and digestive tracts, and secretions in the vagina.

The next line of defense involves white blood cells (leukocytes) that travel through the bloodstream and into tissues, searching for and attacking microorganisms and other invaders.

This defense has 2 parts:

• Innate immunity

• Acquired immunity

Innate (natural) immunity: Innate means something a person is born with. So innate immunity does not require a previous encounter with a microorganism or other invader to work effectively. It responds to invaders immediately, without needing to learn to recognize them. Several types of white blood cells are involved:

• Phagocytes ingest invaders. Phagocytes include macrophages, neutrophils, monocytes, and dendritic cells.

• Natural killer cells are formed ready to recognize and kill cancer cells and cells that are infected with certain viruses.

• Some white blood cells (such as basophils and eosinophils) release substances involved in inflammation, such as cytokines, and in allergic reactions, such as histamine. Some of these cells can destroy invaders directly.

Acquired (adaptive or specific) immunity: In acquired immunity, white blood cells called lymphocytes (B cells and T cells) encounter an invader, learn how to attack it, and remember the specific invader so that they can attack it even more efficiently the next time they encounter it. Acquired immunity takes time to develop after the initial encounter with a new invader because the lymphocytes must adapt to it. However, thereafter, response is quick. B cells and T cells work together to destroy invaders. To be able to recognize invaders, T cells need help from cells called antigen-presenting cells (such as dendritic cells—see figure How T Cells Recognize Antigens). These cells ingest an invader and break it into fragments.

Innate immunity and acquired immunity interact, influencing each other directly or through molecules that attract or activate other cells of the immune system—as part of the mobilization step in defense. These molecules include

• Cytokines (which are the messengers of the immune system)

• Antibodies

• Complement proteins (which form the complement system)

These substances are not contained in cells but are dissolved in a body fluid, such as plasma (the liquid part of blood).

Some of these molecules, including some cytokines, promote inflammation.

Inflammation occurs because these molecules attract immune system cells to the affected tissue. To help get these cells to the tissue, the body sends more blood to the tissue. To carry more blood to the tissue, blood vessels expand and become more porous, allowing more fluids and cells to leave blood vessels and enter the tissue. Inflammation thus tends to cause redness, warmth, and swelling. In people who have dark skin, redness can be subtle. The purpose of inflammation is to contain the infection so that it does not spread. Then other substances produced by the immune system help the inflammation resolve and damaged tissues heal. Although inflammation may be bothersome, it indicates that the immune system is doing its job. However, excessive or long-term (chronic) inflammation can be harmful.

The immune system includes several organs in addition to cells dispersed throughout the body. These organs are classified as primary or secondary lymphoid organs.

The primary lymphoid organs are the sites where white blood cells are produced and/or multiply:

• The bone marrow produces all the different types of white blood cells, including neutrophils, eosinophils, basophils, monocytes, B cells, and the cells that develop into T cells (T cell precursors).

• In the thymus, T cells multiply and are trained to recognize foreign antigens and to ignore the body’s own antigens. T cells are critical for acquired immunity.

When needed to defend the body, the white blood cells are mobilized, mainly from the bone marrow. They then move into the bloodstream and travel to wherever they are needed.

Lymphatic System: Helping Defend Against Infection

The lymphatic system is a vital part of the immune system, along with the thymus, bone marrow, spleen, tonsils, appendix, and Peyer patches in the small intestine. The lymphatic system is a network of lymph nodes connected by lymphatic vessels. This system transports lymph throughout the body. Lymph is formed from fluid that seeps through the thin walls of capillaries into the body's tissues. This fluid contains oxygen, proteins, and other nutrients that nourish the tissues. Some of this fluid reenters the capillaries and some of it enters the lymphatic vessels (becoming lymph). Small lymphatic vessels connect to larger ones and eventually form the thoracic duct. The thoracic duct is the largest lymphatic vessel. It joins with the subclavian vein and thus returns lymph to the bloodstream. Lymph also transports foreign substances (such as bacteria), cancer cells, and dead or damaged cells that may be present in tissues into the lymphatic vessels and to lymph nodes for disposal. Lymph contains many white blood cells. All substances transported by the lymph pass through at least one lymph node, where foreign substances can be filtered out and destroyed before fluid is returned to the bloodstream. In the lymph nodes, white blood cells can collect, interact with each other and with antigens, and generate immune responses to foreign substances. Lymph nodes contain a mesh of tissue that is tightly packed with B cells, T cells, dendritic cells, and macrophages. Harmful microorganisms are filtered through the mesh, then identified and attacked by B cells and T cells. Lymph nodes are often clustered in areas where the lymphatic vessels branch off, such as the neck, armpits, and groin.

The secondary lymphoid organs include the

• Spleen

• Lymph nodes

• Tonsils

• Appendix

• Peyer patches in the small intestine

These organs trap microorganisms and other foreign substances and provide a place for mature cells of the immune system to collect, interact with each other and with the foreign substances, and generate a specific immune response.

The lymph nodes are strategically placed in the body and are connected by an extensive network of lymphatic vessels—the lymphatic system. The lymphatic system transports microorganisms, other foreign substances, cancer cells, and dead or damaged cells from the tissues to the lymph nodes, where these substances and cells are filtered out and destroyed. Then the filtered lymph is returned to the bloodstream.

Lymph nodes are one of the first places that cancer cells can spread. Thus, doctors often evaluate lymph nodes to determine whether a cancer has spread. Cancer cells in a lymph node can cause the node to swell. Lymph nodes can also swell after an infection because acquired immune responses to infections are generated in lymph nodes. Sometimes lymph nodes swell because bacteria that are carried to a lymph node are not killed and cause an infection in the lymph node (lymphadenitis).

To be able to destroy invaders, the immune system must first recognize them. That is, the immune system must be able to distinguish what is nonself (foreign) from what is self. The immune system can make this distinction because all cells have identification molecules (antigens) on their surface. Microorganisms are recognized because the identification molecules on their surface are foreign.

In people, the most important self-identification molecules are called

• Human leukocyte antigens (HLA), which is also called the major histocompatibility complex (MHC)

HLA molecules are called antigens because if transplanted, as in a kidney or skin graft, they can provoke an immune response in another person (normally, they do not provoke an immune response in the person who has them). Each person has an almost unique combination of HLAs. Each person’s immune system normally recognizes this unique combination as self. A cell with molecules on its surface that are not identical to those on the body’s own cells is identified as being foreign. The immune system then attacks that cell. Such a cell may be a cell from transplanted tissue or one of the body’s cells that has been infected by an invading microorganism or altered by cancer. (HLA molecules are what doctors try to match when a person needs an organ transplant.)

How T Lymphocytes Recognize An...

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Some white blood cells—B cells (B lymphocytes)—can recognize invaders directly. But others—T cells (T lymphocytes)—need help from cells called antigen-presenting cells:

• Antigen-presenting cells ingest an invader and break it into fragments.

• The antigen-presenting cell then combines antigen fragments from the invader with the cell's own HLA molecules.

• The combination of antigen fragments and HLA molecules is moved to the cell’s surface.

• A T cell with a matching receptor on its surface can attach to part of the HLA molecule presenting the antigen fragment, as a key fits into a lock.

• The T cell is then activated and begins fighting the invaders that have that antigen.

How T Cells Recognize Antigens

T cells are part of the immune surveillance system. They travel through the bloodstream and lymphatic system. When they reach the lymph nodes or another secondary lymphoid organ, they look for foreign substances (antigens) in the body. However, before they can fully recognize and respond to a foreign antigen, the antigen must be processed and presented to the T cell by another white blood cell, called an antigen-presenting cell. Antigen-presenting cells consist of dendritic cells (which are the most effective), macrophages, and B cells.

White blood cells are activated when they recognize invaders. For example, when the antigen-presenting cell presents antigen fragments bound to HLA to a T cell, the T cell attaches to the fragments and is activated. B cells can be activated directly by invaders. Once activated, white blood cells ingest or kill the invader or do both. Usually, more than one type of white blood cell is needed to kill an invader.

Immune cells, such as macrophages and activated T cells, release substances that attract other immune cells to the trouble spot, thus mobilizing defenses. The invader itself may release substances that attract immune cells.

The immune response must be regulated to prevent extensive damage to the body, as occurs in autoimmune disorders. Regulatory (suppressor) T cells help control the response by secreting cytokines (chemical messengers of the immune system) that inhibit immune responses. These cells prevent the immune response from continuing indefinitely.

Resolution involves confining the invader and eliminating it from the body. After the invader is eliminated, most white blood cells self-destruct and are ingested. Those that are spared are called memory cells. The body retains memory cells, which are part of acquired immunity, to remember specific invaders and respond more vigorously to them at the next encounter.

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