18.5: Adaptive Immune System

The Kiss of Death

The photomicrograph in Figure \(\PageIndex{1}\) illustrates a group of killer T cells (green and red) surrounding a cancer cell (blue, center). When a killer T cell contacts a cancer cell, it binds to and spreads over the target. The killer T cell then uses special chemicals stored in vesicles (red) to deliver the killing blow. This event has thus been nicknamed “the kiss of death.” After the target cell is killed, the killer T cells move on to find the next victim. Killer T cells like these are important players in the adaptive immune system.

Figure \(\PageIndex{1}\): Three Killer T cells surrounding Cancer Cells. Killer T cells surrounded by Cancer Cells, NIH CC0

The adaptive immune system is a subsystem of the overall immune system. It is composed of highly specialized cells and processes that eliminate specific pathogens and tumor cells. An adaptive immune response is initiated by antigens the immune system recognizes as foreign. Unlike an innate immune response, an adaptive immune response is highly specific to a particular pathogen (or its antigen). An important function of the adaptive immune system that is not shared by the innate immune system is the creation of immunological memory or immunity. This occurs after the initial response to a specific pathogen. It allows a faster, stronger response on subsequent encounters with the same pathogen, usually before the pathogen can cause symptoms of illness.

Lymphocytes are the main cells of the adaptive immune system. They are leukocytes that arise and mature in organs of the lymphatic system, including the bone marrow and thymus. The human body normally has about 2 trillion lymphocytes, which constitute about a third of all leukocytes. Most lymphocytes are normally sequestered within tissue fluid or the organs of the lymphatic system, including the tonsils, spleen, and lymph nodes. Only about 2 percent of the lymphocytes are normally circulating in the blood. There are two main types of lymphocytes involved in adaptive immune responses, called T cells and B cells. T cells destroy infected cells or release chemicals that regulate immune responses. B cells secrete antibodies that bind to antigens of pathogens, allowing them to be removed by other immune cells or processes.

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T Cells

There are multiple types of T cells or T lymphocytes. Major types are killer (or cytotoxic) T cells and helper T cells. Both types develop from immature T cells that become activated by exposure to an antigen.

T Cell Activation

T cells must be activated. After the pathogen is phagocytized and digested by macrophages, a portion of it is displayed on the macrophage's surface. The proteins that display the antigen (a part of the pathogen) are called Major Histocompatibility Complex (MHC) proteins. There are two types of MHC, MHCI and MHCII. Therefore, macrophages are called antigen-presenting cells as shown in Figure \(\PageIndex{2}\) and Figure \(\PageIndex{3}\). B lymphocytes can also act as antigen-presenting cells. Helper T cells are more easily activated than killer T cells. Activation of killer T cells is strongly regulated and may require additional stimulation from helper T cells.

Helper T Cells

Activated helper T cells do not kill infected or cancerous cells. Instead, their role is to “manage” both innate and adaptive immune responses by directing other cells to perform these tasks. They control other cells by releasing cytokines. These are proteins that can influence the activity of many cell types, including cytotoxic killer T cells (sometimes referred to as only killer T cells), B cells, and macrophages. For example, some cytokines released by helper T cells help activate killer T cells.

Figure \(\PageIndex{2}\): After getting activated by an antigen-presenting cell, helper T cells trigger various other cells of the immune system, such as activation of B cells to produce antibodies, recruitment and activation of macrophages, and activation of cytotoxic killer T cells. In this image, APC stands for antigen-presenting cells, and CD4+ stands for Cluster Differentiation glycoprotein, which is present on the surface of helper T cells. T cell receptors, Charles Molnar, CC-BY 4.0

Killer T Cells (Cytotoxic T Cells)

When infected body cells present pathogen antigen to a killer T cell, it gets activated (see lower panel of Figure \(\PageIndex{3}\)). Activated killer T cells induce the death of cells that bear a specific non-self antigen because they are infected with pathogens or are cancerous. The antigen targets the cell for destruction by killer T cells, which travel through the bloodstream in search of target cells to kill. Killer T cells may use various mechanisms to kill target cells. One way is by releasing toxins in granules that enter and kill infected or cancerous cells (Figure \(\PageIndex{3}\)).

Figure \(\PageIndex{3}\): Naïve CD4+ (Helper) T cells engage MHC II molecules on antigen-presenting cells (APCs) and become activated. Clones of the activated helper T cell, in turn, activate B cells and CD8+ T (killer) cells, which become cytotoxic T cells. Cytotoxic T cells kill infected cells. Lymphocyte activation, Mikael Häggström CC0

B Cells and B Cell Activation

B cells, or B lymphocytes, are the major cells involved in producing antibodies that circulate in blood plasma and lymph. Antibodies are large, Y-shaped proteins used by the immune system to identify and neutralize foreign invaders. Besides producing antibodies, B cells may also function as antigen-presenting cells or secrete cytokines that help control other immune cells and responses.

Before B cells can actively function to defend the host, they must be activated. As shown in Figure \(\PageIndex{4}\), B cell activation begins when a B cell engulfs and digests an antigen. The antigen may be either free-floating or bound to the pathogen. B cells internalize the antigen and present it on their MHC to a helper T cell. The T cell activates and secretes cytokines that help the B cell multiply and its daughter cells mature into plasma cells and memory B cells. Plasma B cells produce antibodies.

Figure \(\PageIndex{4}\): B cells are activated and become antibody-producing plasma cells with the help of helper T cells. B cell activation, Fred the Oyster CC0

Plasma Cells

Plasma cells are antibody-secreting cells that form from activated B cells. Each plasma cell is like a tiny antibody factory. It may secrete millions of copies of an antibody, each of which can bind to the specific antigen that activated the original B cell. The specificity of an antibody to a specific antigen is illustrated in Figure \(\PageIndex{5}\). When antibodies bind with antigens, it makes the cells bearing them easier targets for phagocytes to find and destroy. Antibody-antigen complexes may also trigger the complement system of the innate immune system, which destroys the cells in a cascade of protein enzymes. In addition, the complexes are likely to clump together (agglutinate). If this occurs, they are filtered out of the blood in the spleen or liver.

Figure \(\PageIndex{5}\): Each antibody fits its antigen like a lock fits a key. Antibody, Fvasconcellos CC0

Immunity

Most activated T cells and B cells die within a few days after a pathogen is cleared from the body. However, a few of the cells survive and remain in the body as memory T cells or memory B cells. These memory cells are ready to mount an immediate response if they are exposed to the same antigen again. This is the basis of immunity.

The earliest known reference to the concept of immunity relates to the bubonic plague (Figure \(\PageIndex{6}\)). In 430 B.C., a Greek historian and general named Thucydides noted that people who had recovered from a previous bout of the plague could nurse people sick with the plague without contracting the illness a second time. We now know that this is true of many diseases and that it results from active immunity.

Figure \(\PageIndex{6}\): Dead, blackened tissues at the fingertips and other extremities are a sign of the bubonic plague, giving rise to its other name, the black death. Acral gangrene of digits, CDC CC0

Active Immunity

Active immunity is the ability of the adaptive immune system to resist a specific pathogen because it has formed an immunological memory of the pathogen. Active immunity is adaptive because it occurs throughout an individual's lifetime, as an adaptation to infection with a specific pathogen, and prepares the immune system for future challenges from that pathogen. Active immunity can come about naturally or artificially.

Naturally Acquired Active Immunity

Active immunity is acquired naturally when a pathogen invades the body, triggering the adaptive immune system. When the initial infection is over, memory B cells and memory T cells remain, providing immunological memory of the pathogen. As long as the memory cells are alive, the immune system is ready to mount an immediate response if the same pathogen tries to infect the body again.

Artificially Acquired Active Immunity

Active immunity can also be acquired artificially through immunization. Immunization is the deliberate exposure of a person to a pathogen in order to provoke an adaptive immune response and the formation of memory cells specific to that pathogen. The pathogen is introduced in a vaccine — usually by injection, sometimes by nose or mouth (Figure \(\PageIndex{7}\)) — so immunization is also called vaccination.

Figure \(\PageIndex{7}\): This young child is receiving an oral polio vaccine. Polio drops, USAID CC0

In a vaccine, only part of a pathogen, a weakened form of the pathogen, or a dead pathogen is typically used. This causes an adaptive immune response without making the immunized person sick. This is how you most likely became immune to diseases such as measles, mumps, and chickenpox. Immunizations may last for a lifetime or require periodic booster shots to maintain immunity. While immunization generally has long-lasting effects, it usually takes several weeks to develop full immunity.

Immunization is the most effective method ever discovered in preventing infectious diseases. As many as 3 million deaths are prevented each year because of vaccinations. Widespread immunity from vaccination is largely responsible for the worldwide eradication of smallpox and the near elimination of several other infectious diseases from many populations, including polio and measles. Immunization is so successful because it exploits the natural specificity and inducibility of the adaptive immune system.

Passive Immunity

Passive immunity results when pathogen-specific antibodies or activated T cells are transferred to a person who has never been exposed to the pathogen. Passive immunity provides immediate protection from a pathogen, but the adaptive immune system does not develop immunological memory to protect the host from the same pathogen in the future. Unlike active immunity, passive immunity lasts only as long as the transferred antibodies or T cells survive in the blood. This is usually between a few days and a few months. However, like active immunity, passive immunity can be acquired both naturally and artificially.

Naturally Acquired Passive Immunity

Passive immunity is acquired naturally by a fetus through its mother’s blood. Antibodies are transported from mother to fetus across the placenta, so babies have high levels of antibodies at birth. Their antibodies have the same range of antigen specificity as their mother’s. Passive immunity may also be acquired by an infant through the mother’s breast milk. This provides young infants with protection against common pathogens in their environment while their immune systems mature.

Artificially Acquired Passive Immunity

Older children and adults can acquire passive immunity artificially by receiving antibodies or activated T cells. This may be done when there is a high risk of infection and insufficient time for the body to develop active immunity through vaccination. It may also be done to reduce symptoms of ongoing disease or to compensate for immunodeficiency diseases (for the latter, see the concept Disorders of the Immune System).

Adaptive Immune Evasion

Many pathogens have been around for a long time, living with human populations for generations. To persist, some have evolved mechanisms to evade the adaptive immune system of human hosts. One way they have done this is by rapidly changing their non-essential antigens. This is called antigenic variation. An example of a pathogen that takes this approach is the human immunodeficiency virus (HIV). It mutates rapidly, so the proteins on its viral envelope are constantly changing. By the time the adaptive immune system responds, the virus’s antigens have changed. Antigenic variation is the main reason that efforts to develop a vaccine against HIV have not yet been successful.

Another evasion strategy some pathogens may use is to mask pathogen antigens with host molecules so the host’s immune system cannot detect them. HIV takes this approach as well. The envelope that encloses the virus is derived from the host cell's outer membrane.

Feature: My Human Body

If you think that immunizations are just for kids, think again. The CDC recommends several vaccines for people over 18. This link shows the vaccine schedule recommended for all adults aged 19 years and older. Additional vaccines may be recommended for certain adults based on specific medical conditions or other indications. Are you up to date with your vaccines? You can check with your doctor to be sure.

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Watch this video to learn about the recent status of HIV vaccine development: