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19.2: Functions of the Lymphatic and Immune Systems

  • Page ID
    22395
  • By the end of this section, you will be able to:

    • Explain the overall functions of the lymphatic system
    • Describe the temporal organization of the immune system
    • Distinguish primary and secondary adaptive immune responses

    Functions of the Lymphatic System

    The functions of the lymphatic system are integral to the immune system because structures of the lymphatic system function to produce, develop, house and distribute leukocytes, but the lymphatic system also supports other body systems in a couple of ways. A network of lymphatic vessels provide a one-way route to return excess fluid from tissues back to the bloodstream to maintain blood volume and also distribute leukocytes throughout the body. Along the way, the fluid is filtered for pathogens and debris as it passes through lymph nodes. Lymphatic capillaries serving the small intestine also collect lipid products of digestion that are too large to enter blood capillaries. These lipids are transported to the bloodstream via the lymphatic vessels. Lymph is the watery fluid connective tissue found in lymphatic vessels whose cellular components include primarily lymphocytes along with phagocytic macrophages and other specialized leukocytes. The watery matrix of lymph is similar to the plasma of blood; it contains dissolved nutrients, waste products, and plasma proteins.

    Lymphoid tissues and organs are so-called because they contain fluid that resembles lymph, and they support lymphocyte production, development, storage, and functions in a variety of locations in the body. Dense collections of leukocytes suspended in reticular connective tissue that remove debris and fight infection within organs of other body systems constitute lymphoid tissues such as the tonsils and mucosa-associated lymphoid tissues (MALT). The lymphatic system also includes distinct organs that support the immune system including the thymus, spleen, and red bone marrow. The vessels, tissues, and organs of the lymphatic system are summarized in Figure \(\PageIndex{1}\) and Table \(\PageIndex{1}\) and will be covered in more detail in subsequent sections of this chapter.

    Organs of the lymphatic system
    Figure \(\PageIndex{1}\): Anatomy of the Lymphatic System. Lymphatic vessels, with lymph nodes along their length, as well as the tonsils, thymus, spleen, and red bone marrow are all organs of the lymphatic system. (Image credit: "Anatomy of the Lymphatic System" by OpenStax is licensed under CC BY 3.0)
    Table \(\PageIndex{1}\). Structures of the Lymphatic System
    Structure Examples Functions
    Lymphatic Vessels Lymphatic capillaries, vessels, trunks, and ducts containing lymph
    • Return excess fluid from tissues to the bloodstream
    • Distribute lymphocytes and other leukocytes throughout the body
    • Transport lipid products of digestion to the bloodstream
    Lymphoid Tissues Tonsils, Mucosa-Associated Lymphoid Tissue (MALT)
    • Support lymphocyte production, storage, and distribution
    Lymphoid Organs Lymph Nodes, Thymus, Red Bone Marrow, Spleen
    • Support lymphocyte production, storage, and distribution
    • Filter blood and lymph of debris, abnormal cells, and pathogens

    The Organization of Immune Function

    The structures of the lymphatic system play integral roles in supporting the immune system, which is responsible for ridding the body of cellular debris and abnormal cells as well as preventing and fighting infection.

    The immune system is a collection of barriers, cells, and soluble proteins that interact and communicate with each other in extraordinarily complex ways. The modern model of immune function is organized into three phases based on the timing of their effects. The three temporal phases or lines of defense are summarized in Table \(\PageIndex{2}\).

    Table \(\PageIndex{2}\). Organization of the Immune System's Lines of Defense

    Line of Defense

    Temporal Response

    Type of Immunity

    Description

    Function(s)

    First Line of Defense

    Instantaneous

    Innate

    Barrier defenses such as skin and mucus membranes

    Prevent pathogenic invasion into the body tissues

    Second Line of Defense

    Rapid

    Innate

    Non-specific internal defenses including cells, soluble factor, inflammatory response

    • Discover and slow the progression of pathogenic infection,
    • Rid the body of debris, including dead and abnormal cells,
    • Promote healing after tissue damage

    Third Line of Defense

    Slow

    Adaptive

    Specific responses mediated by lymphocytes

    • Eradicate pathogenic infection
    • Retain memory for secondary response

    The functions of the immune system are woven into the anatomy of every body system. Innate immunity refers to defenses that are present from birth, including both the infection-preventing barrier defenses and the cellular and physiological internal defenses that respond if the barrier defenses are breached. The innate internal immune responses are non-specific and designed to discover and slow the progression of an infection-causing pathogen (Figure \(\PageIndex{2}\)). A pathogen is any agent capable of causing infection, such as a virus, bacterium, or fungal organism. Adaptive immune responses are designed to recognize, destroy, and retain a memory of a specific pathogen by adapting to each specific pathogen after it is discovered in the body.

    Diagram of the Cooperative Elements of Innate and Adaptive Immunity
    Figure \(\PageIndex{2}\): Cooperation between Elements of Innate and Adaptive Immunity. The innate immune system includes barrier defenses aimed at preventing infection and internal defenses aimed at slowing the spread of infection while activating adaptive immunity. Adaptive immune responses are slower but most effective in eradicating infection. (Image credit: "Cooperation Between Innate and Immune Responses" by OpenStax is licensed under CC BY 3.0)

    Barrier Defenses

    Epithelial barriers are consistently present and optimized for barrier defense as well as their other functions. Epithelial tissues near the outside of the body produce specialized secretions that physiologically enhance the physical barriers to further deter potential infection. For example, the inside of the nose has an epithelial barrier with hairs and a coating of mucus that function to trap pathogens. Further, in areas that are exposed to the environment, body fluids such as sweat, sebum, and urine have antimicrobial properties and also maintain conditions, such as lipid content or pH, that encourage the growth of beneficial microorganisms. The combination of these beneficial microorganisms living on or inside the body on the apical surface of epithelial tissues constitutes the microbiome, and its population size outnumbers human cells in the body. The microbiome is an important part of barrier defenses because one of its roles is to out-compete pathogenic microorganisms to prevent infection.

    Cooperation between Innate and Adaptive Immunity

    In the event a pathogen successfully penetrates the barrier defenses and enters the body, its detection by the immune system will solicit a dynamic response. The innate internal defenses include cells and physiological responses that function to slow the spread of infection. Physiological responses include inflammation, triggered by histamine secreted by basophils and/or mast cells, and the complement system, in which proteins and other molecules participate in fighting the infection to slow its progression. These physiological responses will not be covered in detail here.

    Cells of the innate internal immune response do not recognize specific antigens like the lymphocytes of the adaptive immune response. Instead they have receptors that recognize patterns in the surface antigens that simply distinguish whether any immune response is warranted. If a cell or particle is recognized as "self", a normally functioning part the body, no immune response is warranted. However, if a cell or particle is recognized as "non-self" because the pattern of surface antigens signify it does not belong in the body, a dynamic immune response is triggered. Detection of pathogens or even your own cells that are abnormal because they may be pre-cancerous or infected by an intracellular pathogen such as a virus will solicit a response. The adaptive immune response requires cooperation with elements of innate immunity, but also specialized structures of the lymphatic system from which to coordinate adaptive responses.

    Phagocytes: Macrophages, Dendritic Cells, and Neutrophils

    A phagocyte is a cell that is able to surround and engulf a particle or cell, a process called phagocytosis. The phagocytes of the immune system engulf other particles or cells, either to clean an area of debris, old cells, or to kill pathogens. The phagocytes are the body’s fast-acting defense against microorganisms that have breached barrier defenses and have entered the vulnerable tissues of the body.

    Many of the cells of the immune system have a phagocytic ability, at least at some point during their life cycles. Phagocytosis is an important and effective mechanism of destroying pathogens during innate immune responses. The phagocyte takes the organism inside itself as a phagosome, which subsequently fuses with a lysosome containing digestive enzymes that effectively kill most pathogens. On the other hand, some bacteria including Mycobacteria tuberculosis, the cause of tuberculosis, may be resistant to these enzymes and are therefore much more difficult to clear from the body. Macrophages, neutrophils, and dendritic cells are the major phagocytes of the immune system.

    A macrophage is an irregularly shaped phagocyte that is the most versatile of the phagocytes in the body. Macrophages move through tissues and squeeze through capillary walls using foot-like extensions called pseudopodia. They not only participate in innate immune responses but have also evolved to cooperate with lymphocytes to facilitate the adaptive immune response. Macrophages exist in many tissues of the body, either freely roaming through connective tissues or fixed to reticular fibers within specific tissues such as lymph nodes. When pathogens breach the body’s barrier defenses, macrophages are the first responders in lymphoid and connective tissues outside the bloodstream. Dendritic cells are similar to macrophages, but have slightly more branched shape to further increase their surface area (thus the name, dendr- refers to a tree branch). Dendritic cells are typically found in epithelial tissues. Both macrophages and dendritic cells are antigen-presenting cells (APCs), meaning they present fragments of the antigens belonging to pathogens they have engulfed and destroyed to T lymphocytes to activate the adaptive immune response. A monocyte is a circulating precursor cell that differentiates into either a macrophage or dendritic cell, which can be rapidly attracted to areas of infection by signal molecules of inflammation.

    Natural Killer Cells (NK Cells)

    Natural killer cells (NK cells) are a type of lymphocyte that belongs to the innate internal immune response. NK cells have the ability to induce apoptosis, that is programmed cell death, in cells infected with intracellular pathogens such as bacteria and viruses. NK cells recognize these cells by mechanisms that are still not well understood, but that presumably involve their surface receptors. NK cells can induce apoptosis, in which a cascade of events inside the cell causes its self destruction. If apoptosis is induced before the virus has the ability to synthesize and assemble all its components, no infectious virus will be released from the cell, thus preventing further infection.

    Innate internal immune responses (and early adaptive responses) are in many cases ineffective at completely controlling pathogen growth. However, they slow pathogen growth and allow time for the adaptive immune response to strengthen and either control or eliminate the pathogen. The innate immune system also sends signals to the cells of the adaptive immune system, guiding them in how to attack the pathogen. Thus, these are the two important arms of the immune response.

    The Benefits of the Adaptive Immune Response

    Three aspects of the adaptive immune response make it particularly effective: specificity, immunological memory, and self-recognition. All three of these benefits are made possible by the unique physiological mechanisms of lymphocyte development and proliferation. Lymphocytes are stored in many tissues and organs of the lymphatic system that are strategically located throughout the body ready to be activated and coordinate adaptive responses.

    The specificity of the adaptive immune response—its ability to specifically recognize and make a response against a wide variety of pathogens—is its great strength. Antigens, the small chemical groups often associated with pathogens, are recognized by receptors on the surface of B and T lymphocytes. The adaptive immune response to these antigens is so versatile that it can respond to nearly any pathogen.

    Upon first exposure to a new pathogen, a naïve T cell is activated and expresses a receptor that specifically corresponds to the antigen of the pathogen. The activated T cell then rapidly divides creating an army of lymphocytes expressing that same specific receptor to fight off the pathogen, as well as an army of memory cells to retain T cells that have adapted to the specific pathogen for some time (depending on the pathogen, these memory cells could last for months or for a lifetime). If exposed to the same pathogen again, the memory cells will re-activate a rapid secondary response that will overwhelm the pathogen before symptoms present. This is known as immunological memory.

    A third important feature of the adaptive immune response is its ability to distinguish between self-antigens, those that are normally present in the body, and non-self antigens, those that might be on a potential pathogen. As T and B cells mature, there are mechanisms in place that prevent them from recognizing self-antigen, preventing a damaging immune response against the body. These mechanisms are not 100 percent effective, however, and their breakdown leads to autoimmune diseases, which will be discussed later in this chapter.

    T Cell-mediated Immune Responses

    The immune system’s first exposure to a pathogen is called a primary adaptive immune response. Symptoms of a first infection, called primary disease, are always relatively severe because it takes time for an initial adaptive immune response to a pathogen to become effective.

    In the case primary adaptive immune response, naïve T cells (naïve because they have not yet developed specificity for a particular antigen), such as those stored in the tonsils, become activated to recognize a specific antigen and begin dividing rapidly by mitosis. Each T cell clone has a receptor specific for a particular antigen “hard-wired” into its DNA, and all of its progeny will have identical DNA and T cell receptors, forming clones of the original T cell that will recognize the antigen of a specific pathogen. This proliferation of T cells is called clonal expansion and is necessary to make the immune response strong enough to effectively control a pathogen.

    During a primary adaptive immune response, both memory T cells and effector T cells are generated. Effector T cells act immediately to eradicate the pathogen. Memory T cells are longer-lived and, depending on the pathogen, can even persist for a lifetime. Memory cells are primed to act rapidly upon re-exposure to the same pathogen, generating a secondary adaptive immune response that is stronger and faster than the primary response. This rapid, secondary adaptive response generates large numbers of effector T cells so fast that the pathogen is often overwhelmed before it can cause any symptoms of disease. This is what is meant by immunity to a disease. The same pattern of primary and secondary immune responses occurs in B cells and the antibody response.

    Types of T Cells

    Helper T cells (Th, T4, or CD4+ T cells) interact with the antigen-presenting cells like macrophages and dendritic cells. Helper T cells activate other types of T cells and B cells to mount a response to a specific antigen, but they activate innate immune cells as well by secreting cytokine signaling molecules.

    Cytotoxic T cells (Tc, T8, or CD8+ T cells) are T cells that kill target cells by inducing apoptosis (programmed cell death) using the same mechanism as NK cells. As was discussed earlier with NK cells, killing a virally infected cell before the virus can complete its replication cycle results in the production of no infectious particles. As more cytotoxic T cells are developed during an immune response, they overwhelm the ability of the virus to cause disease. In addition, each cytotoxic T cell can kill more than one target cell, making them especially effective. Cytotoxic T cells are so important in the antiviral immune response that some speculate that this was the main reason the adaptive immune response evolved in the first place.

    Regulatory T cells, or suppressor T cells, are the most recently discovered of the types listed here, so less is understood about them. Exactly how they function is still under investigation, but it is known that they suppress other T cell immune responses. This is an important feature of the immune response, because if clonal expansion during immune responses were allowed to continue uncontrolled, these responses could lead to autoimmune diseases and other medical issues.

    Not only do T cells directly destroy pathogens, but they regulate nearly all other types of the adaptive immune response as well.

    B Lymphocytes and Antibodies

    Antibodies were the first component of the adaptive immune response to be characterized by scientists working on the immune system. It was already known that individuals who survived a bacterial infection were immune to re-infection with the same pathogen. Early microbiologists took serum from an immune patient and mixed it with a fresh culture of the same type of bacteria, then observed the bacteria under a microscope. The bacteria became clumped in a process called agglutination. When a different bacterial species was used, the agglutination did not happen. Thus, there was something in the serum of immune individuals that could specifically bind to and agglutinate bacteria.

    Scientists now know the cause of the agglutination is an antibody molecule, also called an immunoglobulin. What is an antibody? An antibody protein is essentially a secreted form of the antigen-specific receptor. Not surprisingly, the same genes encode both the secreted antibodies and the surface receptors; just one minor difference in the way these proteins are synthesized distinguishes them.

    Antibodies circulate in the blood plasma to alert the immune system to the presence of the matching antigen (and thereby the pathogen). Antibodies have several mechanisms by which they participate in physiological immune responses. For example, in the case of a virus, agglutination (binding of the antibodies to antigens) may prevent the pathogen from infecting a cell and reproducing by blocking the ability of the virus to bind its target cell.

    B Cell Activation and Clonal Selection

    After a naïve B cell is activated by binding to its corresponding antigen, it undergoes clonal expansion, producing both memory B cells and cells that differentiate into plasma cells.

    • Memory B cells function in a way similar to memory T cells. They lead to a stronger and faster secondary response when compared to the primary response.
    • Plasma cells produce and secrete antibodies specifically corresponding to the antigen that activated the naïve B cell. After secreting antibodies for a specific period, they die, as most of their energy is devoted to making antibodies and not to maintaining themselves.

    Clonal selection and expansion of B cells, as well as the primary and secondary immune response phases, work similarly to those of T cells and are depicted in Figure \(\PageIndex{3}\)). Eventually, the plasma cells secrete antibodies with antigenic specificity identical to those that were on the surfaces of the selected B cells. Many identical clones of both plasma cells and memory B cells are generated simultaneously. Upon a second exposure to the same pathogen, the corresponding memory B cell becomes activated to divide and create additional memory B cells and plasma cells that will produce and secrete antibodies.

    Lymphocyte primary responses create cloned effector cells to fight the pathogen and retain memory cells for potential secondary responses in the future.
    Figure \(\PageIndex{3}\): Comparison of Primary and Secondary B Lymphocyte Responses. During a primary B cell immune response, both antibody-secreting plasma cells and memory B cells are produced by mitotic cell division. Memory cells allow for the differentiation of more plasma cells and memory B cells during secondary responses upon subsequent exposure to the same antigen. (Image credit: "Clonal Selection of B Cells" by OpenStax is licensed under CC BY 3.0)

    Concept Review

    Structures of the lymphatic system support immune system function, but also carry out other specific functions. Lymphatic structures include vessels, tissues, and distinct organs. The immune system can be organized into temporal lines of defense that include the innate barrier defenses, non-specific innate internal immune responses, and the adaptive immune response. The adaptive immune response is mediated by T and B lymphocytes. Primary adaptive lymphocyte responses describe the slow but steady clonal expansion of lymphocytes programmed to respond to a specific antigen and eradicate it after primary infection. The primary adaptive lymphocyte response also yields long-lived memory T and B cells that can allow a more rapid adaptive immune response upon secondary infection with the same antigen-containing pathogen.

    Review Questions

    Q. Which enzymes in macrophages are important for clearing intracellular bacteria?

    A. metabolic

    B. mitochondrial

    C. nuclear

    D. lysosomal

    Answer

    Answer: D

    Q. Which of the following cells is phagocytic?

    A. plasma cell

    B. macrophage

    C. B cell

    D. NK cell

    Answer

    Answer: B

    Q. Which of the following cells is important in the innate immune response?

    A. B cells

    B. T cells

    C. macrophages

    D. plasma cells

    Answer

    Answer: C

    Q. Which type of immune response works in concert with cytotoxic T cells against virally infected cells?

    A. natural killer cells

    B. complement

    C. antibodies

    D. memory

    Answer

    Answer: A

    Critical Thinking Questions

    Q. Distinguish primary and secondary adaptive immune responses to a viral infection.

    Answer

    A. A primary adaptive immune response occurs in response to the first exposure to a new viral infection. An antigen from the virus is presented to a helper T lymphocyte by an antigen-presenting cell (typically a macrophage or dendritic cell). T and B lymphocytes are cloned, forming effector and memory cells. Effector cells (cytotoxic T cells and plasma cells) that will work to eradicate the virus immediately. Cytotoxic T cells will induce apoptosis (programmed cell death) in cells infected with the virus. Plasma cells will produce and secrete antibodies to target the antigen of the virus. Memory cells are longer-lived cells that will activate a secondary immune response in case of a future exposure to the same antigen-containing virus.

    Glossary

    adaptive immune response
    relatively slow but very specific and effective immune response controlled by lymphocytes
    antibody
    antigen-specific protein secreted by plasma cells; immunoglobulin
    antigen
    molecule recognized by the receptors of B and T lymphocytes
    antigen-presenting cell (APC)
    cell that presents a fragment of an antigen to T cells to induce an adaptive immune response
    barrier defenses
    antipathogen defenses deriving from a barrier that physically prevents pathogens from entering the body to establish an infection
    B cells
    lymphocytes that act by differentiating into an antibody-secreting plasma cell
    cytotoxic T cells (Tc, T8, or CD8+ T cells)
    T lymphocytes with the ability to induce apoptosis in target cells
    dendritic cell
    phagocyte and antigen-presenting cell (APC) typically found in epithelial tissues such as the epidermis
    effector T cells
    immune cells with a direct, adverse effect on a pathogen
    first line of defense
    temporal classification for the barrier defenses of the immune system that serve to prevent infection
    helper T cells (Th, T4, or CD4+ T cells)
    T cells that secrete cytokines to enhance other immune responses, involved in activation of both B and T cell lymphocytes
    immune system
    series of barriers, cells, and soluble mediators that combine to response to infections of the body with pathogenic organisms
    innate internal immune response
    rapid but relatively nonspecific immune response
    macrophage
    amoeboid phagocyte found in several tissues throughout the body; also an APC
    memory T cells
    long-lived immune cell reserved for future exposure to an pathogen
    microbiome
    the combination of beneficial microorganisms living on and inside the human body
    monocyte
    precursor to macrophages and dendritic cells seen in the blood
    naïve lymphocyte
    mature B or T cell that has not yet encountered antigen for the first time
    neutrophil
    phagocytic white blood cell recruited from the bloodstream to the site of infection via the bloodstream
    pathogen
    any microorganism or acellular particle that causes infection; examples include viruses (acellular), bacteria, fungi, protozoans, and parasitic worms
    phagocytosis
    movement of material from the outside to the inside of the cells via vesicles made from invaginations of the plasma membrane
    plasma cell
    differentiated B cell that is actively secreting antibody
    natural killer cell (NK)
    cytotoxic lymphocyte of innate immune response
    second line of defense
    temporal classification for the innate immune response that rapidly, but nonspecifically responds to pathogens to slow the spread of infection and also promotes healing after tissue damage
    T cell
    lymphocyte that acts by secreting molecules that regulate the immune system or by causing the destruction of foreign cells, viruses, and cancer cells
    third line of defense
    temporal classification for the adaptive immune response that responds more slowly, but also specifically and more effectively to eradicate infection

    Contributors and Attributions