Immune Response

If pathogens manage to get through the body’s first two lines of defense, a third line of defense takes over. This third line of defense is often referred to as the immune response. This defense is specific to a particular pathogen, and it allows the immune system to “remember” the pathogen after the infection is over. If the pathogen tries to invade the body again, the immune system can launch a much faster, stronger attack. This lets the immune system destroy the pathogen before it can cause harm. The immune response mainly involves the lymphatic system.

Lymphatic System

The lymphatic system is a major component of the immune system. Because of its important role in the immune system, the terms ”immune system” and ”lymphatic system” are sometimes used interchangeably. However, nonspecific defenses of the body include organs such as the skin, which is not part of the lymphatic system. In addition, the lymphatic system has another function not directly related to defense.

Functions of the Lymphatic System

The lymphatic system has three basic functions. The first function is related to digestion. The other functions are involved in the immune response.

1. The lymphatic system absorbs fatty acids after the digestion of lipids in the small intestine. It then transports the fatty acids to the bloodstream, where they circulate throughout the body.
2. The lymphatic system removes excess fluid from body tissues and returns the fluid to the blood. The fluid is filtered as it passes through the lymphatic system, and any pathogens it contains are destroyed before the fluid enters the bloodstream.
3. The lymphatic system produces lymphocytes. Lymphocytes are the type of white blood cells, or leukocytes, primarily involved in the immune response. They recognize and help destroy specific foreign invaders in body fluids and cells.

Parts of the Lymphatic System

The lymphatic system, which is shown in Figure 1, consists of lymphatic organs, lymphatic vessels, lymph, and lymph nodes. Organs of the lymphatic system include the red bone marrow, thymus, spleen, and tonsils.

• Red bone marrow is found inside many bones, including the hip, breast, and skull bones. It produces leukocytes.
• The thymus is a gland located in the upper chest behind the breast bone. It stores and matures lymphocytes.
• The spleen is a gland in the upper abdomen. It filters blood and destroys worn-out red blood cells. Lymphocytes in the spleen destroy any pathogens filtered out of the blood.
• Tonsils are glands on either side of the pharynx in the throat. They trap pathogens, which are then destroyed by lymphocytes in the tonsils.

Figure 1: Human lymphatic system.

Lymphatic vessels make up a body-wide circulatory system, similar to the arteries and veins of the cardiovascular system. However, lymphatic vessels circulate lymph instead of blood. Lymph is fluid that leaks out of tiny blood vessels, called capillaries, into spaces between cells in tissues. At sites of inflammation, there is usually more lymph around cells, and it is likely to contain many pathogens.

Unlike the cardiovascular system, the lymphatic system does not have a pump to force lymph through its vessels. Lymph circulates due to peristalsis of lymphatic vessels and rhythmic contractions of the skeletal muscles that surround the vessels. Valves in the lymphatic vessels prevent lymph from flowing backwards through the system.

As lymph accumulates between cells, it diffuses into tiny lymphatic vessels. The lymph then moves through the lymphatic system, from smaller to larger vessels, until it reaches the main lymphatic ducts in the chest. Here, the lymph drains into the bloodstream.

Before lymph reaches the bloodstream, pathogens are filtered out of it at lymph nodes. Lymph nodes are small, oval structures located along the lymphatic vessels that act like filters. Any pathogens filtered out of the lymph at lymph nodes are destroyed by lymphocytes in the nodes.

Lymphocytes

Lymphocytes are the key cells involved in the immune response. There are an estimated two trillion lymphocytes in the human body, and they make up about 25 percent of all leukocytes. Usually, fewer than half the body’s lymphocytes are found in the blood. The rest are found in the lymphatic system, where they are most likely to encounter pathogens.

The immune response depends on two types of lymphocytes: B lymphocytes, or B cells, and T lymphocytes, or T cells. Both types of lymphocytes are produced in the red bone marrow. The two types are named for the sites where they mature. B cells mature in the red bone marrow, and T cells mature in the thymus. Both B and T cells can recognize and respond to specific pathogens. B or T cells that respond to the body’s own molecules as though they were foreign, or “nonself,” receive a signal that causes them to die. Only those B and T cells that have shown they are unlikely to react to “self” molecules are released into the circulation.

Antigen Recognition

B and T cells do not actually recognize and respond to pathogens but to the antigens they carry. Antigens are protein molecules that the immune system recognizes as non-self. Any protein that can trigger an immune response because it is foreign to the body is called an antigen. Antigens include proteins on pathogens, cancer cells, and the cells of transplanted organs.

Antigen Receptors

Both B and T cells can “recognize” specific antigens because they have receptor molecules on their surface that bind to particular antigen molecules or pieces of antigen molecules. As shown in Figure 2, the fit between a receptor molecule and a specific antigen is like a lock and key. Receptors on each B or T cell recognize and bind to just one type of antigen. The human body makes lymphocytes with receptor sites for a huge number of possible antigens that may be encountered throughout a person’s life.

Figure 2: A receptor molecule on the surface of a lymphocyte binds to a particular antigen like a lock and key.

Activation of Lymphocytes

Before lymphocytes can function, they must be activated. Activation occurs the first time the cells encounter their specific antigens after leaving the red bone marrow or thymus. Until these circulating B and T cells have been activated, they are called “naïve” cells.

Humoral Immune Response

B cells are responsible for the humoral immune response. The humoral immune response takes place in blood and lymph and involves the production of antibodies. Antibodies are large, Y-shaped proteins called immunoglobulins (Ig) that recognize and bind to antigens. In humans (and other mammals) there are five types of immunoglobulins: IgA, IgD, IgE, IgG, and IgM. Antibodies are produced by activated B cells.

B Cell Activation

Naïve B cells are activated by an antigen in the sequence of events shown in Figure 3. A B cell encounters its matching antigen and engulfs it. The B cell then displays fragments of the antigen on its surface. This attracts a helper T cell (which you will read about below). The helper T cell binds to the B cell at the antigen site and releases cytokines. Cytokines are chemical signals used to communicate between cells. Cytokines from the helper T cell stimulate the B cell to develop into plasma cells or memory cells.

Figure 3: After engulfing an antigen, a naïve B cell presents the antigen to a mature T cell. The T cell, in turn, releases cytokines that activate the B cell. Once activated, the B cell can produce antibodies to that particular pathogen.

Plasma Cells and Antibody Production

Plasma cells are activated B cells that secrete antibodies. They are specialized to act like antibody factories. Antibodies produced by plasma cells circulate in the blood and lymph. Each antibody recognizes and binds to a specific antigen, depending on the plasma cell that produced it and other factors. The binding of an antibody to its matching antigen forms an antigen-antibody complex, as shown in Figure 4. An antigen-antibody complex flags a pathogen or foreign cell for destruction by phagocytosis. The liver removes antigen-antibody complexes from the blood and the spleen removes them from the lymph.

Figure 4: An antibody molecule has an area that “fits” one particular antigen. This area is where the antigen binds to the antibody, creating an antigen-antibody complex.

Memory Cells

Whereas most plasma cells live just a few days, memory cells live much longer. They may even survive for the lifetime of the individual. Memory cells are activated B (or T) cells that retain a “memory” of a specific pathogen long after an infection is over. They help launch a rapid response against the pathogen if it invades the body in the future. Memory B cells remain in the lymph, ready to produce specific antibodies against the same pathogen if it shows up in body fluids again.

Cell-Mediated Immune Response

There are several different types of T cells, including helper, cytotoxic, memory, and regulatory T cells. T cells are responsible for cell-mediated immunity. Cell-mediated immunity involves the destruction of body cells that are infected with pathogens or have become damaged or cancerous.

T Cell Activation

The different types of naïve T cells are activated in the same general way. The mechanism is shown in Figure 5. It involves B cells or leukocytes such as macrophages. These other cells engulf pathogens in phagocytosis and display parts of the pathogens’ antigens on their surface. The cells are then called antigen-presenting cells. When a naïve T cell encounters one of these cells with an antigen matching its own, it begins the activation process. After T cells are activated, the various types of T cells play different roles in the immune response.

Figure 5: A naïve T cell is activated when it encounters a B cell or macrophage that has engulfed a pathogen and presents the pathogen’s antigen on its surface.

Helper T Cells

Activated helper T cells do not kill pathogens or destroy infected cells, but they are still necessary for the immune response. In fact, they are considered to be the “managers” of the immune response. After activation, helper T cells divide rapidly and secrete cytokines. These chemical signals control the activity of other lymphocytes. As mentioned above, cytokines from helper T cells activate B cells. They also activate other T cells.

Most activated helper T cells die out once a pathogen has been cleared from the body. However, some helper T cells remain in the lymph as memory cells. These memory cells are ready to produce large numbers of antigen-specific helper T cells if they are exposed to the same antigen again in the future.

Cytotoxic T Cells

Helper cells are needed to activate cytotoxic T cells. Activated cytotoxic T cells destroy tumor cells, damaged cells, and cells infected with viruses. They are also involved in the rejection of transplanted organs. Once activated, a cytotoxic T cell divides rapidly and produces an “army” of cells identical to itself. These cells travel throughout the body “searching” for more cells carrying their specific antigen. Whenever they encounter the cells, they destroy them. Illustrated in Figure 6 is how a cytotoxic T cell destroys a body cell infected with viruses. The cytotoxic T cell releases toxins that form pores, or holes, in the infected cell’s membrane. This causes the cell to burst, destroying both the cell and the viruses inside it.

Figure 6: A cytotoxic T cell releases toxins that destroy an infected body cell and the viruses it contains.

After cytotoxic T cells bring a viral infection under control, most of the cytotoxic T cells die off. However, some of them remain as memory cells. If the same pathogen tries to infect the body again, the memory cells mount an effective immune response by producing a new army of antigen-specific cytotoxic T cells.

Regulatory T Cells

Regulatory T cells shut down cell-mediated immunity toward the end of an immune response. They also try to suppress any T cells that react against self antigens as though they were foreign. This occurs in automimmune diseases.

Immunity

Memory B and T cells help protect you from re-infection by pathogens that have infected you in the past. Being able to resist a pathogen in this way is called immunity. Immunity can be active or passive.

Active Immunity

Active immunity is immunity that results from a pathogen stimulating an immune response and leaving you with memory cells for the specific pathogen. This happens when a pathogen infects your body and makes you sick. As long as the memory cells survive, the pathogen will be unlikely to re-infect you and make you sick again. In the case of some pathogens, memory cells and active immunity last for the life of the individual.

Active immunity can also occur through immunization. Immunization is deliberate exposure of a person to a pathogen in order to provoke an immune response. The purpose of immunization is to prevent actual infections by the pathogen. The pathogen is typically injected. However, only part of a pathogen, a weakened form of the pathogen, or a dead pathogen is used. This provokes an immune response without making you sick. Diseases you have likely been immunized against include measles, mumps, rubella, whooping cough, and chicken pox.

Passive Immunity

Passive immunity is humoral immunity that results when antibodies to a specific pathogen are transferred to an individual who has never been exposed to the pathogen before. Passive immunity lasts only as long as the antibodies survive in body fluids, generally between a few days and several months.

Passive immunity is acquired by a fetus when it receives antibodies from the mother’s blood. It is acquired by an infant when it receives antibodies from the mother’s milk. Older children and adults can acquire passive immunity through injection of antibodies into the blood. Injection of antibodies is sometimes used as treatment for a disease, such as measles, when people have not been immunized against the disease.