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20.5: Adaptive Immune System

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  • The Kiss of Death

    The photomicrograph in Figure \(\PageIndex{1}\) shows a group of killer T cells (green and red) surrounding a cancer cell (blue, center). When a killer T cell makes contact with the cancer cell, it attaches to and spreads over the dangerous 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.

    Killer T cells surround a cancer cell
    Figure \(\PageIndex{1}\): Image used with permission (Public Domain; The National Institutes of Health, via Wikimedia Commons).

    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 set in motion by antigens that 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 of the lymphocytes are normally sequestered within tissue fluid or 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 with antigens of pathogens so they can be removed by other immune cells or processes.

     

    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 to become either killer T cells or helper T cells. This requires the presentation of a foreign antigen by antigen-presenting cells, as shown in the figure below. Antigen-presenting cells may be dendritic cells, macrophages, or B cells. Activation occurs when T cells are presented with a foreign antigen coupled with an MHC self-antigen. 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.

    T cell activation

    Figure \(\PageIndex{2}\): Exposure to a foreign antigen on an antigen-presenting cell is necessary to activate T cells to become killer T cells or helper T cells. Image used with permission (Hazmat2; public domain; via Wikicommons; T Cell activation.png)

    Killer T Cells

    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 searching for 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 \(\PageIndex{3}\)).

    helper and cytotoxic T cells activation
    Figure \(\PageIndex{3}\): Naïve CD4+ 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 cells, which become cytotoxic T cells. Cytotoxic T cells kill infected cells. (opentextbc.ca/biology/; adaptive-immune-response; CC BY 3.0)

    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 killer T cells, B cells, and macrophages. For example, some cytokines released by helper T cells help activate killer T cells

    Lymphocyte activation
    Figure \(\PageIndex{4}\): Helper T cells trigger various other cells of the immune system to begin their tasks. In this image, APC stands for antigen presenting cells and CD4+ stands for Cluster Differentiation glycoprotein which is present on the cell surface of the immune system. Image used with permission ( Mikael Häggström, 2014; public domain; Medical gallery; via Wikimedia.org; Lymphocyte activation simple.png)

    B Cells and B Cell Activation

    B cells, or B lymphocytes, are the major cells involved in the creation of 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 \(\PageIndex{5}\), B cell activation begins when a B cell engulfs and digests an antigen. The antigen may be either free-floating in the lymph or it may be presented by an antigen-presenting cell such as a dendritic cell or macrophage. In either case, the B cell then displays antigen fragments bound to its own MHC antigens. The MHC-antigen complex on the B cell attracts helper T cells. The helper T cells, in turn, secrete cytokines that help the B cell to multiply and the daughter cells to mature into plasma cells.

    B cell activation
    Figure \(\PageIndex{5}\): B cells are activated and become antibody-producing plasma cells with the help of helper T cells. Image used with permission (Fred the Oyster; public domain; via wikimedia.org; B cell activation.svg)

    Plasma Cells

    Antibody
    Figure \(\PageIndex{6}\): Each antibody fits its antigen like a lock fits a key. Image used with permission (Fvasconcellos 19:03, 6 May 2007 (UTC) [Public domain] via Wikimedia.org; Antibody.svg)

    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 the figure below. 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.

    Immunity

    Most activated T cells and B cells die within a few days once a pathogen has been 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 activate an immediate response if they are exposed to the same antigen again in the future. This is the basis of immunity.

    The earliest known reference to the concept of immunity relates to the bubonic plaque (see photo below). 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 it occurs because of active immunity.

    Acral gangrene due to plague
    Figure \(\PageIndex{7}\): 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. Image used with permission (Public Domain; Centers for Disease Control and Prevention).

    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 during the lifetime of an individual 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 and activates the adaptive immune system. When the initial infection is over, memory B cells and memory T cells remain that provide 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 (see the photo below) — so immunization is also called vaccination.

    Poliodrops
    Figure \(\PageIndex{8}\): This young child is receiving an oral polio vaccine. Image used with permission (Public Domain; USAID).

    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 chicken pox. 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 due to vaccinations is largely responsible for the worldwide eradication of smallpox and the near elimination of several other infectious diseases from many populations, including such diseases as 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 specificities as their mother’s. Passive immunity may also be acquired by an infant through the mother’s breast milk. This gives young infants protection from common pathogens in their environment while their own immune system matures.

    Artificially Acquired Passive Immunity

    Older children and adults can acquire passive immunity artificially through the injection of 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 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 approach some pathogens may take is to mask pathogen antigens with host molecules so the host’s immune system cannot detect the antigens. HIV takes this approach as well. The envelope that covers the virus is formed from the outermost membrane of the host cell.

    Feature: My Human Body

    If you think that immunizations are just for kids, think again. There are several vaccines recommended by the CDC for people over the age of 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.

    Summary

    • The adaptive immune system is a subsystem of the overall immune system that recognizes and makes a tailored attack against specific pathogens or tumor cells. It is a slower but more effective response than the innate immune response and also leads to immunity to particular pathogens.
    • Lymphocytes produced by the lymphatic system are the main cells of the adaptive immune system. There are two major types of lymphocytes: T cells and B cells. Both types must be activated by foreign antigens to become functioning immune cells.
    • Most activated T cells become either killer T cells or helper T cells. Killer T cells destroy cells that are infected with pathogens or are cancerous. Helper T cells manage immune responses by releasing cytokines that control other types of leukocytes.
    • Activated B cells form plasma cells that secrete antibodies, which bind to specific antigens on pathogens or infected cells. The antibody-antigen complexes generally lead to the destruction of the cells, for example, by attracting phagocytes or triggering the complement system.
    • After an adaptive immune response occurs, long-lasting memory B cells and memory T cells may remain to confer immunity to the specific pathogen that caused the adaptive immune response. These memory cells are ready to activate an immediate response if they are exposed to the same antigen again in the future.
    • Immunity may be active or passive. Active immunity occurs when the immune system has been presented with antigens that elicit an adaptive immune response. This may occur naturally as the result of an infection or artificially as the result of immunization. Active immunity may last for years or even for life.
    • Passive immunity occurs without an adaptive immune response by the transfer of antibodies or activated T cells. This may occur naturally between a mother and her fetus or her nursing infant, or it may occur artificially by injection. Passive immunity lasts only as long as the antibodies or activated T cells remain alive in the body, generally just weeks or months.
    • Many pathogens have evolved mechanisms to evade the adaptive immune system. For example, human immunodeficiency virus (HIV) evades the adaptive immune system by frequently changing its antigens and by forming its outer envelope from the host’s cell membrane.

    Review

    1. What is the adaptive immune system?
    2. Describe the main cells of the adaptive immune system.
    3. How are lymphocytes activated?
    4. Identify two common types of T cells and their functions.
    5. How do activated B cells help defend against pathogens?
    6. Define immunity.
    7. What are two ways active immunity may come about?
    8. How does passive immunity differ from active immunity?
    9. How may passive immunity occur?
    10. What ways of evading the human adaptive immune system evolved in human immunodeficiency virus (HIV)?
    11. Describe two ways in which B cells and T cells work together to generate adaptive immune responses.
    12. Which cells directly kill pathogen-infected or cancerous cells?

      A. Plasma cells

      B. Killer T cells

      C. Helper T cells

      D. All of the above

    13. Why do vaccinations involve the exposure of a person to a version of a pathogen?

    14. True or False. Immunization is a form of passive immunity.

    15. True or False. Antibodies transmitted from mother to child via breast milk cause the formation of memory B cells and long-term immunity.

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