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The spleen is the largest organ of the lymphatic system and acts as a blood filter and a site for immune responses. It contains immune cells, such as lymphocytes and macrophages, that destroy old red blood cells and fight infections and pathogens in the blood, similar to how lymph nodes filter lymph. The spleen also produces lymphocytes and stores platelets.

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Adaptive immunity occurs after exposure to an antigen either from a pathogen or a vaccination.The adaptive, or acquired, immune response takes days or even weeks to become established—much longer than the innate response; however, adaptive immunity is more specific to an invading pathogen. This part of the immune system works in tandem with the innate immune response to neutralize pathogens. In fact, without information from the innate immune system, the adaptive response could not be mobilized.

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Two main functions of the lymphatic system is for immunity and fluid balance.

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Lymphatic System: Definition, Anatomy, Function, Parts, and Common Diseases - Learning Junction

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The primary structures of the lymphatic system are:

1. Red bone marrow

2. thymus

The secondary structures of the lymphatic system are:

1. Tonsils

2. Lymph nodes

3. Spleen

4. MALT

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primary and secondary structures of the lymphatic system

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Listen to the audio recording to learn about the thymus

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Key relationships to the lymphatic system

Largest lymphatic organ:

The spleen is the largest organ in the lymphatic system, which is a network of tissues and vessels that help the body fight infection.

Blood filtration:

Instead of filtering lymph like lymph nodes, the spleen filters blood. It removes old and damaged red blood cells and other cellular debris.

Immune function:

The spleen is a "secondary lymphoid organ," meaning it's a site where immune responses are initiated. Its white pulp contains immune cells that detect and fight pathogens, while the red pulp removes old red blood cells and stores white blood cells and platelets.

Immune cell production:

The spleen produces and matures lymphocytes, which are crucial for the immune response.

Storage of immune cells and platelets:

It acts as a storage site for white blood cells and platelets, releasing them when the body needs them, such as after an injury.

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Lymph is watery fluid that flows through your lymphatic system. Lymph (pronounced “limf”) helps your lymphatic system support your overall health, from providing nutrients to cells and tissues to protecting your body from foreign intruders like viruses, bacteria and cancerous cells.

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As blood flows through your capillaries, some plasma oozes through tiny holes in your capillary walls. This plasma, now called lymph, moves into your tissues and the spaces around your cells to deliver oxygen, proteins and other nutrients. At the same time, lymph sweeps up debris like damaged and cancerous cells, bacteria and viruses. Lymph also picks up extra fluid from your tissues and cells that your capillaries can’t absorb.

Loaded down with extra fluid and harmful organisms, like damaged or dangerous cargo, lymph then moves into lymphatic capillaries that carry lymph back through your body. As it travels, lymph goes through lymph nodes. Lymph nodes are lymph quality control, searching lymph cargo for harmful organisms to be destroyed by white blood cells (lymphocytes). The filtered lymph eventually returns to your bloodstream.

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Lymphoma is cancer that affects the lymphatic system. The lymphatic system is made up of organs, glands, tubelike vessels and clusters of cells called lymph nodes. It's part of the body's germ-fighting immune system. Lymphoma can affect lymph nodes, blood, bone marrow, spleen, and other tissues throughout the body, such as in the gastrointestinal system, central nervous system, bones or skin.

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What are common conditions and disorders that affect lymph?

Lymph needs to keep moving. There are conditions that make that difficult:

Lymphedema happens when lymph can’t flow into lymphatic capillaries. When that happens, lymph starts to build up in soft tissues in your arms and legs, making them swell. Lymphedema often affects people who had surgery to remove lymph nodes or had radiation treatment.

Elephantiasis (lymphatic filariasis) blocks your lymphatic system so lymph can’t flow through the system. As happens with lymphedema, lymph begins to build up and your arms, legs or genitals start swelling.Parasites carried by mosquitoes cause elephantiasis.

Cancerous tumors that block lymphatic ducts or lymph nodes may affect how lymph moves around your body.

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Key roles of lymph in the immune system

Transportation:

Lymphatic vessels transport lymph fluid, which contains waste products, damaged cells, bacteria, and viruses, away from tissues and to lymph nodes. They also carry immune cells throughout the body.

Filtering:

Lymph nodes act as filters, trapping and removing harmful substances like bacteria, viruses, and cancer cells from the lymph fluid.

Immune cell storage and activation:

Lymph nodes are packed with immune cells, particularly T cells and B cells. When a pathogen is detected in the lymph, these nodes stimulate the production of more white blood cells to fight the infection.

Immune response initiation:

Lymph nodes are key sites for initiating an adaptive immune response. When pathogens are transported to a lymph node, they can trigger an immune response, leading to the creation of antibodies and memory cells to fight future infections.

Production of immune cells:

Organs within the lymphatic system, such as the bone marrow and thymus, are major sites for the production and maturation of lymphocytes (T and B cells).

Fluid balance and fat absorption:

While not a direct immune function, the lymphatic system's role in returning excess fluid to the bloodstream and absorbing fats from the intestine is crucial for maintaining the overall health of the body, which is essential for a functioning immune system.

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Immunity is an organism’s ability by which it defends itself from diseases. It prevents development of disease inside the body. There are two types of immunity, innate immunity and acquired immunity. Innate immunity, also called inborn immunity, is inherited from parents and is present by birth. It is not specific, it acts the same for all intruders entering the body. Protection is provided in the form of barriers in this type of immunity. There are four types of barriers present in innate immunity which keeps intruders from entering the body and causing disease. They are-
>Physical barriers- the physical barriers prevent the entry of pathogens and foreign agents into the body. Physical barriers include skin, mucus, digestive tract membranes, and traps of respiratory and urogenital which traps entering microorganisms.
>Physiological barriers- these barriers are physiological secretions. Their function is to prevent growth of microorganisms which are capable of passing the physical barrier. These include sweat, saliva, tears and acid secreted in the stomach.
>Cellular barriers- these barriers destroy and eliminate microbes that enter the body. It is carried out by white blood cells such as leukocytes, monocytes, natural killer cells, and macrophage. They do so by phagocytosis.
>Cytokine barriers- the cells which have been infected by virus starts secreting interferons which prevents the spread of infection. They protect the non-infected cells from infection.

Note:Immunity present by birth is called innate immunity, it is of four types; physical, physiological, cellular and cytokine. This type of immunity is not as strong as acquired immunity.

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Vaccination is based on the knowledge that exposure to noninfectious antigens, derived from known pathogens, generates a mild primary immune response. Vaccines usually contain either weakened or dead microbes, or fragments of molecules found on pathogens that are known to contain antigens.  The also usually contain molecules that stimulate the innate response, since innate immune responses are important in the generation of strong adaptive responses. The immune response to vaccination may not be perceived by the host as illness but still confers immune memory. When exposed to the corresponding pathogen to which an individual was vaccinated, the reaction is similar to a secondary exposure. Because each reinfection generates more memory cells and increased resistance to the pathogen, some vaccine courses involve one or more booster vaccinations to mimic repeat exposures.

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Four Stages of the Adaptive Immune Response

B cells, Helper T cells, and Cytotoxic T cells all respond to antigens in a similar pattern; subsequent sections of this chapter will address the specifics of the immune response in each cell type.  In order for their immune functions to be elicited, the cells must first encounter antigens by binding specifically to them using specialized membrane proteins.  This binding elicits changes in the activity of the immune cells, termed activation, which is the second step in the adaptive immune response.  Activation responses vary between the three types of cells, but in general all involve both changes in gene expression and in the initiation of cell division. Third, the immune cells attack invading pathogens or infected cells.  Depending on the type of lymphocyte, the specific methods used to neutralize pathogens can vary.  In most infections, the attacks from many different lymphocytes, and from cells of the innate immune system, occur simultaneously and the atttacking cells often stimulate each other through chemical messenger such as cytokines.  Finally, long-lived, pre-activated immune cells that wait for a subsequent infection are formed in the memory phase of the adaptive immune response.  These cells are identical to the initial cells that first encountered the pathogen except that they have already undergone the activation step so are able to attack right away when activated again by an antigen.

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Humoral Immune Response: B cells

An antigen is a molecule that stimulates a response in the immune system. B cells participate in a chemical response to antigens present in the body by producing specific antibodies that circulate throughout the body and bind with an antigen whenever it is encountered. This is known as the humoral immune response because it involves molecules secreted into the blood plasma, an acellular fluid or “humor.” During maturation of B cells, a set of highly specific B cells are produced, each with antigen receptor molecules in their membrane.

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Lymphocytes, which are a subclass of white blood cells, are formed with other blood cells in the red bone marrow found in many flat bones, such as the shoulder or pelvic bones. The two types of lymphocytes of the adaptive immune response are B and T cells. Whether an immature lymphocyte becomes a B cell or T cell depends on where in the body it matures. The B cells remain in the bone marrow to mature (hence the name “B” for “bone marrow”), while T cells migrate to the thymus, where they mature (hence the name “T” for “thymus”).  During the maturation process, each B or T cell develops unique surface proteins that are able to recognize a unique set of very specific molecules on antigens (discussed below).  In other words, each B or T cell can recognize only a very few different molecules, but together the entire lymphocyte population in a healthy person should be able to recognize molecules from most pathogens. The specificity of these unique surface proteins, or receptors, on the lymphocytes is determined by the genetics of the individual and is present before a foreign molecule is introduced to the body or encountered. Except in certain immune system diseases called autoimmune diseases, no mature B or T cells are able to recognize and bind to molecules that are found on healthy human cells, but only to molecules found on pathogens or on unhealthy human cells.

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B cells are involved in the humoral immune response, which targets pathogens loose in blood and lymph, and B cells carry out this response by secreting antibodies.T cells are involved in the cell-mediated immune response, which targets infected cells in the body.  T cells include the Helper T cells and the Cytotoxic, or Killer, T cells. Cytotoxic T cells directly kill human cells that are infected or unhealthy. Helper T cells do not directly kill infected cells, but secrete molecules that are crucial for the function of all other cells in the immune response to a pathogen.

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The production of antibodies by plasma cells in response to an antigen is called active immunity and describes the host’s active response of the immune system to an infection or to a vaccination. There is also a passive immune response where antibodies come from an outside source, instead of the individual’s own plasma cells, and are introduced into the host. For example, antibodies circulating in a pregnant female’s body move across the placenta into the developing fetus. Antibodies are also passed to the child in breast milk. The child benefits from the presence of these antibodies for up to several months after birth. In addition, a passive immune response is possible by injecting antibodies into an individual in the form of an antivenom to a snake-bite toxin or antibodies in blood serum to help fight a hepatitis infection. This gives immediate protection since the body does not need the time required to mount its own response.

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Activation of T cells also begins when T cells encounter antigens and bind to them with specific proteins on their cell surfaces, called T cell receptors.  Each T cell’s receptor proteins are able to bind to only one or a few very similar antigens, allowing each one to respond to different pathogens.  Unlike B cells, T lymphocytes are unable to recognize pathogens without assistance. They rely on cells of the innate immune system to help them encounter antigens, and to start the responses required for an immune attack, in a complex process that is beyond the scope of this textbook. T cells that have encountered antigens that bind to their specific receptors in this process, and received important signals from the innate immune cells are considered to be “activated.

There are two main types of T cells: Helper T cells (sometimes called TH) and  Cytotoxic T cells (TC, also known as killer T cells.) The Helper T cells function indirectly to tell other immune cells about potential pathogens. After encountering an antigen, a Helper T cell’s activation causes many rounds of cell division to occur, producing thousands of identical cells that all have the same T cell receptor and all have initiated the expression of genes required for producing and secreting cytokines.  As with B cells, the clone includes active TH cells and inactive memory TH cells.  Helper T cells carry out their attacks on pathogens through the secretion of these cytokines.  These chemical messengers greatly enhance the activities of macrophages, innate immune cells and Cytotoxic T cells, and also stimulate naïve B cells to secrete antibodies. Similar to memory B cells, memory Helper T cells are long-lived, and can carry out a fast response to the same pathogen after decades.

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Although they do not directly kill infected cells, the function of the Helper T cells is crucial for fighting off pathogens. This important function is lost in untreated infection with the Human Immunodeficiency Virus, which causes AIDS (Acquired Immunodeficiency Syndrome.) HIV infects Helper T cells cells using their CD4 surface molecules, gradually depleting the number of Helper T cells in the body; this inhibits the adaptive immune system’s capacity to generate sufficient responses to infection or tumors. As a result, HIV-infected individuals often suffer from infections that would not cause illness in people with healthy immune systems but which can cause devastating illness to immune-compromised individuals.

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Cytotoxic T cells are the key component of the cell-mediated part of the adaptive immune system and attack and destroy infected cells. Cytotoxic cells are particularly important in protecting against viral infections; this is because viruses replicate within cells where they are shielded from extracellular contact with circulating antibodies. Once activated, a cytotoxic T cell creates a large clone of cells with one specific set of cell-surface T cell receptors, as in the case with proliferation of activated B cells and Helper T cells. As with B cells, the clone includes active TC cells and inactive memory TC cells. The resulting active Cytotoxic T  cells then identify infected host cells, bind to them and kill them.  Phagocytes from the innate immune system then clean up the cellular debris, and ingest and destroy any pathogens that were inside of the infected cells. Cytotoxic T cells attempt to identify and destroy infected cells before the pathogen can replicate and escape, thereby halting the progression of intracellular infections. They also support NK lymphocytes to destroy early cancers. Cytokines secreted by activated Helper T cells stimulate cytotoxic T cells and enhance their ability to identify and destroy infected cells and tumors

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A cytotoxic cell fighting off the pathogen.

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Helper T cells getting help to fight the pathogen

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The adaptive immune system has a memory component that allows for a rapid and large response upon reinvasion of the same pathogen. During the adaptive immune response to a pathogen that has not been encountered before, known as the primary immune response, plasma cells secreting antibodies and differentiated T cells increase, then plateau over time. As B and T cells mature into effector cells, a subset of the naïve populations differentiates into B and T memory cells with the same antigen specificities. A memory cell is an antigen-specific B or T lymphocyte that does not differentiate into an effector cell during the primary immune response, but that can immediately become an effector cell on re-exposure to the same pathogen. As the infection is cleared and pathogenic stimuli subside, the effectors are no longer needed and they undergo apoptosis. In contrast, the memory cells persist in the circulation.

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If the pathogen is never encountered again during the individual’s lifetime, B and T memory cells will circulate for a few years or even several decades and will gradually die off, having never functioned as effector cells. However, if the host is re-exposed to the same pathogen type, circulating memory cells will immediately differentiate into plasma cells and active Helper T cells without requiring the help of innate cells, or cytokines from activated Helper T cells. This is known as the secondary immune response. One reason why the adaptive immune response is delayed is because it takes time for naïve B and T cells with the appropriate antigen specificities to be identified, activated, and proliferate. On reinfection, this step is skipped, and the result is a more rapid production of immune defenses. Each of these newly reactivated effector cells also produces a stronger response than the first set of effector cells. For example, memory B cells that differentiate into plasma cells in a secondary immune response output tens to hundreds-fold greater antibody amounts than were secreted during the primary response. This rapid and dramatic antibody response may stop the infection before it can even become established, and before the innate immune system can initiate the inflammatory response that causes symptoms of infection such as fever, redness, swelling and body aches.  The individual may not even realize they had been exposed to the pathogen.

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active immunity

an immunity that occurs as a result of the activity of the body’s own cells rather than from antibodies acquired from an external source

adaptive immunity

a specific immune response that occurs after exposure to an antigen either from a pathogen or a vaccination

antibody

a protein that is produced by plasma cells after stimulation by an antigen; also known as an immunoglobulin

antigen

a macromolecule that reacts with cells of the immune system and which may or may not have a stimulatory effect

B cell

a lymphocyte that matures in the bone marrow

cell-mediated immune response

an adaptive immune response that is controlled by T cells

cytotoxic T lymphocyte (TC)

an adaptive immune cell that directly kills infected cells via enzymes, and that releases cytokines to enhance the immune response

effector cell

a lymphocyte that has differentiated, such as a B cell, plasma cell, or cytotoxic T cell

helper T lymphocyte (TH)

a cell of the adaptive immune system that binds APCs via MHC II molecules and stimulates B cells or secretes cytokines to initiate the immune response

humoral immune response

the adaptive immune response that is controlled by activated B cells and antibodies

lymph

the watery fluid present in the lymphatic circulatory system that bathes tissues and organs with protective white blood cells and does not contain erythrocytes

memory cell

an antigen-specific B or T lymphocyte that does not differentiate into an effector cell during the primary immune response but that can immediately become an effector cell on reexposure to the same pathogen

passive immunity

an immunity that does not result from the activity of the body’s own immune cells but by transfer of antibodies from one individual to another

primary immune response

the response of the adaptive immune system to the first exposure to an antigen

secondary immune response

the response of the adaptive immune system to a second or later exposure to an antigen mediated by memory cells

T cell

a lymphocyte that matures in the thymus gland