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7.2: Anatomy of the Lymphatic and Immune Systems - Biology

7.2: Anatomy of the Lymphatic and Immune Systems - Biology


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Learning Objectives

By the end of this section, you will be able to:

  • Describe the structure and function of the lymphatic tissue (lymph fluid, vessels, ducts, and organs)
  • Describe the structure and function of the primary and secondary lymphatic organs
  • Discuss the cells of the immune system, how they function, and their relationship with the lymphatic system

The immune system is the complex collection of cells and organs that destroys or neutralizes pathogens that would otherwise cause disease or death. The lymphatic system, for most people, is associated with the immune system to such a degree that the two systems are virtually indistinguishable. The lymphatic system is the system of vessels, cells, and organs that carries excess fluids to the bloodstream and filters pathogens from the blood. The swelling of lymph nodes during an infection and the transport of lymphocytes via the lymphatic vessels are but two examples of the many connections between these critical organ systems.

Functions of the Lymphatic System

A major function of the lymphatic system is to drain body fluids and return them to the bloodstream. Blood pressure causes leakage of fluid from the capillaries, resulting in the accumulation of fluid in the interstitial space—that is, spaces between individual cells in the tissues. In humans, 20 liters of plasma is released into the interstitial space of the tissues each day due to capillary filtration. Once this filtrate is out of the bloodstream and in the tissue spaces, it is referred to as interstitial fluid. Of this, 17 liters is reabsorbed directly by the blood vessels. But what happens to the remaining three liters? This is where the lymphatic system comes into play. It drains the excess fluid and empties it back into the bloodstream via a series of vessels, trunks, and ducts. Lymph is the term used to describe interstitial fluid once it has entered the lymphatic system. When the lymphatic system is damaged in some way, such as by being blocked by cancer cells or destroyed by injury, protein-rich interstitial fluid accumulates (sometimes “backs up” from the lymph vessels) in the tissue spaces. This inappropriate accumulation of fluid referred to as lymphedema may lead to serious medical consequences.

As the vertebrate immune system evolved, the network of lymphatic vessels became convenient avenues for transporting the cells of the immune system. Additionally, the transport of dietary lipids and fat-soluble vitamins absorbed in the gut uses this system.

Cells of the immune system not only use lymphatic vessels to make their way from interstitial spaces back into the circulation, but they also use lymph nodes as major staging areas for the development of critical immune responses. A lymph node is one of the small, bean-shaped organs located throughout the lymphatic system.

Practice Questions

Visit this website for an overview of the lymphatic system. What are the three main components of the lymphatic system?
[reveal-answer q=”206834″]Show Answer[/reveal-answer]
[hidden-answer a=”206834″]The three main components are the lymph vessels, the lymph nodes, and the lymph.[/hidden-answer]

Structure of the Lymphatic System

The lymphatic vessels begin as open-ended capillaries, which feed into larger and larger lymphatic vessels, and eventually empty into the bloodstream by a series of ducts. Along the way, the lymph travels through the lymph nodes, which are commonly found near the groin, armpits, neck, chest, and abdomen. Humans have about 500–600 lymph nodes throughout the body.

A major distinction between the lymphatic and cardiovascular systems in humans is that lymph is not actively pumped by the heart, but is forced through the vessels by the movements of the body, the contraction of skeletal muscles during body movements, and breathing. One-way valves (semi-lunar valves) in lymphatic vessels keep the lymph moving toward the heart. Lymph flows from the lymphatic capillaries, through lymphatic vessels, and then is dumped into the circulatory system via the lymphatic ducts located at the junction of the jugular and subclavian veins in the neck.

Lymphatic Capillaries

Lymphatic capillaries, also called the terminal lymphatics, are vessels where interstitial fluid enters the lymphatic system to become lymph fluid. Located in almost every tissue in the body, these vessels are interlaced among the arterioles and venules of the circulatory system in the soft connective tissues of the body. Exceptions are the central nervous system, bone marrow, bones, teeth, and the cornea of the eye, which do not contain lymph vessels.

Lymphatic capillaries are formed by a one cell-thick layer of endothelial cells and represent the open end of the system, allowing interstitial fluid to flow into them via overlapping cells. When interstitial pressure is low, the endothelial flaps close to prevent “backflow.” As interstitial pressure increases, the spaces between the cells open up, allowing the fluid to enter. Entry of fluid into lymphatic capillaries is also enabled by the collagen filaments that anchor the capillaries to surrounding structures. As interstitial pressure increases, the filaments pull on the endothelial cell flaps, opening up them even further to allow easy entry of fluid.

In the small intestine, lymphatic capillaries called lacteals are critical for the transport of dietary lipids and lipid-soluble vitamins to the bloodstream. In the small intestine, dietary triglycerides combine with other lipids and proteins, and enter the lacteals to form a milky fluid called chyle. The chyle then travels through the lymphatic system, eventually entering the liver and then the bloodstream.

Larger Lymphatic Vessels, Trunks, and Ducts

The lymphatic capillaries empty into larger lymphatic vessels, which are similar to veins in terms of their three-tunic structure and the presence of valves. These one-way valves are located fairly close to one another, and each one causes a bulge in the lymphatic vessel, giving the vessels a beaded appearance.

The superficial and deep lymphatics eventually merge to form larger lymphatic vessels known as lymphatic trunks. On the right side of the body, the right sides of the head, thorax, and right upper limb drain lymph fluid into the right subclavian vein via the right lymphatic duct. On the left side of the body, the remaining portions of the body drain into the larger thoracic duct, which drains into the left subclavian vein. The thoracic duct itself begins just beneath the diaphragm in the cisterna chyli, a sac-like chamber that receives lymph from the lower abdomen, pelvis, and lower limbs by way of the left and right lumbar trunks and the intestinal trunk.

The overall drainage system of the body is asymmetrical. The right lymphatic duct receives lymph from only the upper right side of the body. The lymph from the rest of the body enters the bloodstream through the thoracic duct via all the remaining lymphatic trunks. In general, lymphatic vessels of the subcutaneous tissues of the skin, that is, the superficial lymphatics, follow the same routes as veins, whereas the deep lymphatic vessels of the viscera generally follow the paths of arteries.

The Organization of Immune Function

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 consist of the following:

  • Barrier defenses such as the skin and mucous membranes, which act instantaneously to prevent pathogenic invasion into the body tissues
  • The rapid but nonspecific innate immune response, which consists of a variety of specialized cells and soluble factors
  • The slower but more specific and effective adaptive immune response, which involves many cell types and soluble factors, but is primarily controlled by white blood cells (leukocytes) known as lymphocytes, which help control immune responses

The cells of the blood, including all those involved in the immune response, arise in the bone marrow via various differentiation pathways from hematopoietic stem cells. In contrast with embryonic stem cells, hematopoietic stem cells are present throughout adulthood and allow for the continuous differentiation of blood cells to replace those lost to age or function. These cells can be divided into three classes based on function:

  • Phagocytic cells, which ingest pathogens to destroy them
  • Lymphocytes, which specifically coordinate the activities of adaptive immunity
  • Cells containing cytoplasmic granules, which help mediate immune responses against parasites and intracellular pathogens such as viruses

Lymphocytes

As stated above, lymphocytes are the primary cells of adaptive immune responses (see Table 1 for more details). The two basic types of lymphocytes, B cells and T cells, are identical morphologically with a large central nucleus surrounded by a thin layer of cytoplasm. They are distinguished from each other by their surface protein markers as well as by the molecules they secrete. While B cells mature in red bone marrow and T cells mature in the thymus, they both initially develop from bone marrow. T cells migrate from bone marrow to the thymus gland where they further mature. B cells and T cells are found in many parts of the body, circulating in the bloodstream and lymph, and residing in secondary lymphoid organs, including the spleen and lymph nodes, which will be described later in this section. The human body contains approximately 1012 lymphocytes.

B Cells

B cells are immune cells that function primarily by producing antibodies. An antibody is any of the group of proteins that binds specifically to pathogen-associated molecules known as antigens. An antigen is a chemical structure on the surface of a pathogen that binds to T or B lymphocyte antigen receptors. Once activated by binding to antigen, B cells differentiate into cells that secrete a soluble form of their surface antibodies. These activated B cells are known as plasma cells.

T Cells

The T cell, on the other hand, does not secrete antibody but performs a variety of functions in the adaptive immune response. Different T cell types have the ability to either secrete soluble factors that communicate with other cells of the adaptive immune response or destroy cells infected with intracellular pathogens. The roles of T and B lymphocytes in the adaptive immune response will be discussed further in this chapter.

Plasma Cells

Another type of lymphocyte of importance is the plasma cell. A plasma cell is a B cell that has differentiated in response to antigen binding, and has thereby gained the ability to secrete soluble antibodies. These cells differ in morphology from standard B and T cells in that they contain a large amount of cytoplasm packed with the protein-synthesizing machinery known as rough endoplasmic reticulum.

Natural Killer Cells

A fourth important lymphocyte is the natural killer cell, a participant in the innate immune response. A natural killer cell (NK) is a circulating blood cell that contains cytotoxic (cell-killing) granules in its extensive cytoplasm. It shares this mechanism with the cytotoxic T cells of the adaptive immune response. NK cells are among the body’s first lines of defense against viruses and certain types of cancer.

Table 1. Lymphocytes
Type of lymphocytePrimary function
B lymphocyteGenerates diverse antibodies
T lymphocyteSecretes chemical messengers
Plasma cellSecretes antibodies
NK cellDestroys virally infected cells

Primary Lymphoid Organs and Lymphocyte Development

Understanding the differentiation and development of B and T cells is critical to the understanding of the adaptive immune response. It is through this process that the body (ideally) learns to destroy only pathogens and leaves the body’s own cells relatively intact. The primary lymphoid organs are the bone marrow, spleen, and thymus gland. The lymphoid organs are where lymphocytes mature, proliferate, and are selected, which enables them to attack pathogens without harming the cells of the body.

Bone Marrow

In the embryo, blood cells are made in the yolk sac. As development proceeds, this function is taken over by the spleen, lymph nodes, and liver. Later, the bone marrow takes over most hematopoietic functions, although the final stages of the differentiation of some cells may take place in other organs. The red bone marrow is a loose collection of cells where hematopoiesis occurs, and the yellow bone marrow is a site of energy storage, which consists largely of fat cells. The B cell undergoes nearly all of its development in the red bone marrow, whereas the immature T cell, called a thymocyte, leaves the bone marrow and matures largely in the thymus gland.

Thymus

The thymus gland is a bilobed organ found in the space between the sternum and the aorta of the heart. Connective tissue holds the lobes closely together but also separates them and forms a capsule.

Fiugre 6. The thymus lies above the heart. The trabeculae and lobules, including the darkly staining cortex and the lighter staining medulla of each lobule, are clearly visible in the light micrograph of the thymus of a newborn. LM × 100. (Micrograph provided by the Regents of the University of Michigan Medical School © 2012)

View the University of Michigan WebScope to explore the tissue sample in greater detail.

The connective tissue capsule further divides the thymus into lobules via extensions called trabeculae. The outer region of the organ is known as the cortex and contains large numbers of thymocytes with some epithelial cells, macrophages, and dendritic cells (two types of phagocytic cells that are derived from monocytes). The cortex is densely packed so it stains more intensely than the rest of the thymus. The medulla, where thymocytes migrate before leaving the thymus, contains a less dense collection of thymocytes, epithelial cells, and dendritic cells.

Aging and the Immune System

By the year 2050, 25 percent of the population of the United States will be 60 years of age or older. The CDC estimates that 80 percent of those 60 years and older have one or more chronic disease associated with deficiencies of the immune systems. This loss of immune function with age is called immunosenescence. To treat this growing population, medical professionals must better understand the aging process. One major cause of age-related immune deficiencies is thymic involution, the shrinking of the thymus gland that begins at birth, at a rate of about three percent tissue loss per year, and continues until 35–45 years of age, when the rate declines to about one percent loss per year for the rest of one’s life. At that pace, the total loss of thymic epithelial tissue and thymocytes would occur at about 120 years of age. Thus, this age is a theoretical limit to a healthy human lifespan.

Thymic involution has been observed in all vertebrate species that have a thymus gland. Animal studies have shown that transplanted thymic grafts between inbred strains of mice involuted according to the age of the donor and not of the recipient, implying the process is genetically programmed. There is evidence that the thymic microenvironment, so vital to the development of naïve T cells, loses thymic epithelial cells according to the decreasing expression of the FOXN1 gene with age.

It is also known that thymic involution can be altered by hormone levels. Sex hormones such as estrogen and testosterone enhance involution, and the hormonal changes in pregnant women cause a temporary thymic involution that reverses itself, when the size of the thymus and its hormone levels return to normal, usually after lactation ceases. What does all this tell us? Can we reverse immunosenescence, or at least slow it down? The potential is there for using thymic transplants from younger donors to keep thymic output of naïve T cells high. Gene therapies that target gene expression are also seen as future possibilities. The more we learn through immunosenescence research, the more opportunities there will be to develop therapies, even though these therapies will likely take decades to develop. The ultimate goal is for everyone to live and be healthy longer, but there may be limits to immortality imposed by our genes and hormones.

Secondary Lymphoid Organs and their Roles in Active Immune Responses

Lymphocytes develop and mature in the primary lymphoid organs, but they mount immune responses from the secondary lymphoid organs. A naïve lymphocyte is one that has left the primary organ and entered a secondary lymphoid organ. Naïve lymphocytes are fully functional immunologically, but have yet to encounter an antigen to respond to. In addition to circulating in the blood and lymph, lymphocytes concentrate in secondary lymphoid organs, which include the lymph nodes, spleen, and lymphoid nodules. All of these tissues have many features in common, including the following:

  • The presence of lymphoid follicles, the sites of the formation of lymphocytes, with specific B cell-rich and T cell-rich areas
  • An internal structure of reticular fibers with associated fixed macrophages
  • Germinal centers, which are the sites of rapidly dividing B lymphocytes and plasma cells, with the exception of the spleen
  • Specialized post-capillary vessels known as high endothelial venules; the cells lining these venules are thicker and more columnar than normal endothelial cells, which allow cells from the blood to directly enter these tissues

Lymph Nodes

Lymph nodes function to remove debris and pathogens from the lymph, and are thus sometimes referred to as the “filters of the lymph”. Any bacteria that infect the interstitial fluid are taken up by the lymphatic capillaries and transported to a regional lymph node. Dendritic cells and macrophages within this organ internalize and kill many of the pathogens that pass through, thereby removing them from the body. The lymph node is also the site of adaptive immune responses mediated by T cells, B cells, and accessory cells of the adaptive immune system. Like the thymus, the bean-shaped lymph nodes are surrounded by a tough capsule of connective tissue and are separated into compartments by trabeculae, the extensions of the capsule. In addition to the structure provided by the capsule and trabeculae, the structural support of the lymph node is provided by a series of reticular fibers laid down by fibroblasts.

The major routes into the lymph node are via afferent lymphatic vessels. Cells and lymph fluid that leave the lymph node may do so by another set of vessels known as the efferent lymphatic vessels. Lymph enters the lymph node via the subcapsular sinus, which is occupied by dendritic cells, macrophages, and reticular fibers. Within the cortex of the lymph node are lymphoid follicles, which consist of germinal centers of rapidly dividing B cells surrounded by a layer of T cells and other accessory cells. As the lymph continues to flow through the node, it enters the medulla, which consists of medullary cords of B cells and plasma cells, and the medullary sinuses where the lymph collects before leaving the node via the efferent lymphatic vessels.

Spleen

In addition to the lymph nodes, the spleen is a major secondary lymphoid organ. It is about 12 cm (5 in) long and is attached to the lateral border of the stomach via the gastrosplenic ligament. The spleen is a fragile organ without a strong capsule, and is dark red due to its extensive vascularization. The spleen is sometimes called the “filter of the blood” because of its extensive vascularization and the presence of macrophages and dendritic cells that remove microbes and other materials from the blood, including dying red blood cells. The spleen also functions as the location of immune responses to blood-borne pathogens.

The spleen is also divided by trabeculae of connective tissue, and within each splenic nodule is an area of red pulp, consisting of mostly red blood cells, and white pulp, which resembles the lymphoid follicles of the lymph nodes. Upon entering the spleen, the splenic artery splits into several arterioles (surrounded by white pulp) and eventually into sinusoids. Blood from the capillaries subsequently collects in the venous sinuses and leaves via the splenic vein. The red pulp consists of reticular fibers with fixed macrophages attached, free macrophages, and all of the other cells typical of the blood, including some lymphocytes. The white pulp surrounds a central arteriole and consists of germinal centers of dividing B cells surrounded by T cells and accessory cells, including macrophages and dendritic cells. Thus, the red pulp primarily functions as a filtration system of the blood, using cells of the relatively nonspecific immune response, and white pulp is where adaptive T and B cell responses are mounted.

Lymphoid Nodules

The other lymphoid tissues, the lymphoid nodules, have a simpler architecture than the spleen and lymph nodes in that they consist of a dense cluster of lymphocytes without a surrounding fibrous capsule. These nodules are located in the respiratory and digestive tracts, areas routinely exposed to environmental pathogens.

Tonsils are lymphoid nodules located along the inner surface of the pharynx and are important in developing immunity to oral pathogens. The tonsil located at the back of the throat, the pharyngeal tonsil, is sometimes referred to as the adenoid when swollen. Such swelling is an indication of an active immune response to infection. Histologically, tonsils do not contain a complete capsule, and the epithelial layer invaginates deeply into the interior of the tonsil to form tonsillar crypts. These structures, which accumulate all sorts of materials taken into the body through eating and breathing, actually “encourage” pathogens to penetrate deep into the tonsillar tissues where they are acted upon by numerous lymphoid follicles and eliminated. This seems to be the major function of tonsils—to help children’s bodies recognize, destroy, and develop immunity to common environmental pathogens so that they will be protected in their later lives. Tonsils are often removed in those children who have recurring throat infections, especially those involving the palatine tonsils on either side of the throat, whose swelling may interfere with their breathing and/or swallowing.

Mucosa-associated lymphoid tissue (MALT) consists of an aggregate of lymphoid follicles directly associated with the mucous membrane epithelia. MALT makes up dome-shaped structures found underlying the mucosa of the gastrointestinal tract, breast tissue, lungs, and eyes. Peyer’s patches, a type of MALT in the small intestine, are especially important for immune responses against ingested substances. Peyer’s patches contain specialized endothelial cells called M (or microfold) cells that sample material from the intestinal lumen and transport it to nearby follicles so that adaptive immune responses to potential pathogens can be mounted.

Bronchus-associated lymphoid tissue (BALT) consists of lymphoid follicular structures with an overlying epithelial layer found along the bifurcations of the bronchi, and between bronchi and arteries. They also have the typically less-organized structure of other lymphoid nodules. These tissues, in addition to the tonsils, are effective against inhaled pathogens.

Chapter Review

The lymphatic system is a series of vessels, ducts, and trunks that remove interstitial fluid from the tissues and return it the blood. The lymphatics are also used to transport dietary lipids and cells of the immune system. Cells of the immune system all come from the hematopoietic system of the bone marrow. Primary lymphoid organs, the bone marrow and thymus gland, are the locations where lymphocytes of the adaptive immune system proliferate and mature. Secondary lymphoid organs are site in which mature lymphocytes congregate to mount immune responses. Many immune system cells use the lymphatic and circulatory systems for transport throughout the body to search for and then protect against pathogens.

Self Check

Answer the question(s) below to see how well you understand the topics covered in the previous section.

Critical Thinking Question

Describe the flow of lymph from its origins in interstitial fluid to its emptying into the venous bloodstream.

[reveal-answer q=”822756″]Show Answer[/reveal-answer]
[hidden-answer a=”822756″]The lymph enters through lymphatic capillaries, and then into larger lymphatic vessels. The lymph can only go in one direction due to valves in the vessels. The larger lymphatics merge to form trunks that enter into the blood via lymphatic ducts. [/hidden-answer]

Glossary

adaptive immune response: relatively slow but very specific and effective immune response controlled by lymphocytes

afferent lymphatic vessels: lead into a lymph node

antibody: antigen-specific protein secreted by plasma cells; immunoglobulin

antigen: molecule recognized by the receptors of B and T lymphocytes

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

bone marrow: tissue found inside bones; the site of all blood cell differentiation and maturation of B lymphocytes

bronchus-associated lymphoid tissue (BALT): lymphoid nodule associated with the respiratory tract

chyle: lipid-rich lymph inside the lymphatic capillaries of the small intestine

cisterna chyli: bag-like vessel that forms the beginning of the thoracic duct

efferent lymphatic vessels: lead out of a lymph node

germinal centers: clusters of rapidly proliferating B cells found in secondary lymphoid tissues

high endothelial venules: vessels containing unique endothelial cells specialized to allow migration of lymphocytes from the blood to the lymph node

immune system: series of barriers, cells, and soluble mediators that combine to response to infections of the body with pathogenic organisms

innate immune response: rapid but relatively nonspecific immune response

lymph: fluid contained within the lymphatic system

lymph node: one of the bean-shaped organs found associated with the lymphatic vessels

lymphatic capillaries: smallest of the lymphatic vessels and the origin of lymph flow

lymphatic system: network of lymphatic vessels, lymph nodes, and ducts that carries lymph from the tissues and back to the bloodstream.

lymphatic trunks: large lymphatics that collect lymph from smaller lymphatic vessels and empties into the blood via lymphatic ducts

lymphocytes: white blood cells characterized by a large nucleus and small rim of cytoplasm

lymphoid nodules: unencapsulated patches of lymphoid tissue found throughout the body

mucosa-associated lymphoid tissue (MALT): lymphoid nodule associated with the mucosa

naïve lymphocyte: mature B or T cell that has not yet encountered antigen for the first time

natural killer cell (NK): cytotoxic lymphocyte of innate immune response

plasma cell: differentiated B cell that is actively secreting antibody

primary lymphoid organ: site where lymphocytes mature and proliferate; red bone marrow and thymus gland

right lymphatic duct: drains lymph fluid from the upper right side of body into the right subclavian vein

secondary lymphoid organs: sites where lymphocytes mount adaptive immune responses; examples include lymph nodes and spleen

spleen: secondary lymphoid organ that filters pathogens from the blood (white pulp) and removes degenerating or damaged blood cells (red pulp)

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

thoracic duct: large duct that drains lymph from the lower limbs, left thorax, left upper limb, and the left side of the head

thymocyte: immature T cell found in the thymus

thymus: primary lymphoid organ; where T lymphocytes proliferate and mature

tonsils: lymphoid nodules associated with the nasopharynx


7.0 Introduction

Figure 7.0 Lateral View of the Human Skull.

Chapter Objectives

After this chapter, you will be able to:

7.1 Describe the functions of the skeletal system and define its two major subdivisions

7.2 Identify the bones and bony structures of the skull, the cranial suture lines, the cranial fossae, and the openings in the skull

7.3 Discuss the vertebral column and regional variations in its bony components and curvatures

7.4 Describe the components of the thoracic cage

7.5 Discuss the embryonic development of the axial skeleton

The skeletal system forms the rigid internal framework of the body. It consists of the bones, cartilages, and ligaments. Bones support the weight of the body, allow for body movements, and protect internal organs. Cartilage provides flexible strength and support for body structures such as the thoracic cage, the external ear, and the trachea and larynx. At joints of the body, cartilage can also unite adjacent bones or provide cushioning between them. Ligaments are the strong connective tissue bands that hold the bones together at a moveable joint and serve to prevent excessive movements of the joint that would result in injury. Providing force to create movement of the skeleton are the skeletal muscles of the body, which are firmly attached to the skeleton via connective tissue structures called tendons. As muscles contract, they pull on the bones to produce movements of the body. Thus, without a skeleton, you would not be able to stand, run, or even feed yourself!

Each bone of the body serves a particular function, and therefore bones vary in size, shape, and strength based on these functions. For example, the bones of the lower back and lower limb are thick and strong to support your body weight. Similarly, the size of a bony landmark that serves as a muscle attachment site on an individual bone is related to the strength of this muscle. Muscles can apply very strong pulling forces to the bones of the skeleton. Due to these forces, bones develop enlarged bony landmarks at sites where powerful muscles attach. This means that not only the size of a bone, but also its shape, is related to its function. For this reason, the identification of bony landmarks is important during your study of the skeletal system.

Bones are dynamic organs that can modify their density and thickness in response to application of forces and changes in body chemistry. Thus, muscle attachment sites on bones will thicken if you begin a workout program that increases muscle strength. Similarly, the walls of weight-bearing bones will thicken if you gain body weight or begin pounding the pavement as part of a new running regimen. In contrast, a reduction in muscle strength or body weight will cause bones to become thinner. This may happen during a prolonged hospital stay, following limb immobilization in a cast, or going into the weightlessness of outer space. Even a change in diet, such as eating only soft food due to the loss of teeth, will result in a noticeable decrease in the size and thickness of the jaw bones. Changes in hormones such as estrogen and testosterone also cause changes to bone mass as a normal part of development and aging.


Lymphoid organs

The lymphatic system is composed of:

Bone marrow

Bone marrow is a sponge-like tissue found inside the bones. That is where most immune system cells are produced and then also multiply. These cells move to other organs and tissues through the blood. At birth, many bones contain red bone marrow, which actively creates immune system cells. Over the course of our life, more and more red bone marrow turns into fatty tissue. In adulthood, only a few of our bones still contain red bone marrow, including the ribs, breastbone and the pelvis.

Thymus

The thymus is located behind the breastbone above the heart. This gland-like organ reaches full maturity only in children, and is then slowly transformed to fatty tissue. Special types of immune system cells called thymus cell lymphocytes (T cells) mature in the thymus. Among other tasks, these cells coordinate the processes of the innate and adaptive immune systems. T cells move through the body and constantly monitor the surfaces of all cells for changes.

Lymph nodes

Lymph nodes are small bean-shaped tissues found along the lymphatic vessels. The lymph nodes act as filters. Various immune system cells trap germs in the lymph nodes and activate the creation of special antibodies in the blood. Swollen or painful lymph nodes are a sign that the immune system is active, for example to fight an infection.

Spleen

The spleen is located in the left upper abdomen, beneath the diaphragm, and is responsible for different kinds of jobs:

There is always a lot of blood flowing through the spleen tissue. At the same time this tissue is very soft. In the event of severe injury, for example in an accident, the spleen may rupture easily. Surgery is then usually necessary because otherwise there is a danger of bleeding to death. If the spleen needs to be removed completely, other immune system organs can carry out its roles.

Tonsils

The tonsils are also part of the immune system. Because of their location at the throat and palate, they can stop germs entering the body through the mouth or the nose. The tonsils also contain a lot of white blood cells, which are responsible for killing germs. There are different types of tonsils: palatine tonsils, adenoids and the lingual tonsil. All of these tonsillar structures together are sometimes called Waldeyer's ring since they form a ring around the opening to the throat from the mouth and nose.

There is also lymphatic tissue on the side of the throat, which can perform the functions of the palatine tonsils if they are removed.

Mucous membranes

The bowel plays a central role in defending the body against germs: More than half of all the body's cells that produce antibodies are found in the bowel wall, especially in the last part of the small bowel and in the appendix. These cells detect foreign substances, and then mark and destroy them. They also save information about the substances in order to be able to react more quickly the next time. The large bowel also contains harmless bacteria called gastrointestinal or gut flora. Healthy gut flora make it difficult for germs to spread and enter the body.

Mucous membranes support the immune system in other parts of the body, too, such as the respiratory and urinary tracts, and the lining of the vagina. The immune system cells are directly beneath the mucous membranes, where they prevent bacteria and viruses from attaching.


21.1 Anatomy of the Lymphatic and Immune Systems

The immune system is the complex collection of cells and organs that destroys or neutralizes pathogens that would otherwise cause disease or death. The lymphatic system, for most people, is associated with the immune system to such a degree that the two systems are virtually indistinguishable. The lymphatic system is the system of vessels, cells, and organs that carries excess fluids to the bloodstream and filters pathogens from the blood. The swelling of lymph nodes during an infection and the transport of lymphocytes via the lymphatic vessels are but two examples of the many connections between these critical organ systems.

Functions of the Lymphatic System

A major function of the lymphatic system is to drain body fluids and return them to the bloodstream. Blood pressure causes leakage of fluid from the capillaries, resulting in the accumulation of fluid in the interstitial space—that is, spaces between individual cells in the tissues. In humans, 20 liters of plasma is released into the interstitial space of the tissues each day due to capillary filtration. Once this filtrate is out of the bloodstream and in the tissue spaces, it is referred to as interstitial fluid. Of this, 17 liters is reabsorbed directly by the blood vessels. But what happens to the remaining three liters? This is where the lymphatic system comes into play. It drains the excess fluid and empties it back into the bloodstream via a series of vessels, trunks, and ducts. Lymph is the term used to describe interstitial fluid once it has entered the lymphatic system. When the lymphatic system is damaged in some way, such as by being blocked by cancer cells or destroyed by injury, protein-rich interstitial fluid accumulates (sometimes “backs up” from the lymph vessels) in the tissue spaces. This inappropriate accumulation of fluid referred to as lymphedema may lead to serious medical consequences.

As the vertebrate immune system evolved, the network of lymphatic vessels became convenient avenues for transporting the cells of the immune system. Additionally, the transport of dietary lipids and fat-soluble vitamins absorbed in the gut uses this system.

Cells of the immune system not only use lymphatic vessels to make their way from interstitial spaces back into the circulation, but they also use lymph nodes as major staging areas for the development of critical immune responses. A lymph node is one of the small, bean-shaped organs located throughout the lymphatic system.

Interactive Link

Visit this website for an overview of the lymphatic system. What are the three main components of the lymphatic system?

Structure of the Lymphatic System

The lymphatic vessels begin as a blind ending, or closed at one end, capillaries, which feed into larger and larger lymphatic vessels, and eventually empty into the bloodstream by a series of ducts. Along the way, the lymph travels through the lymph nodes, which are commonly found near the groin, armpits, neck, chest, and abdomen. Humans have about 500–600 lymph nodes throughout the body (Figure 21.2).

A major distinction between the lymphatic and cardiovascular systems in humans is that lymph is not actively pumped by the heart, but is forced through the vessels by the movements of the body, the contraction of skeletal muscles during body movements, and breathing. One-way valves (semi-lunar valves) in lymphatic vessels keep the lymph moving toward the heart. Lymph flows from the lymphatic capillaries, through lymphatic vessels, and then is dumped into the circulatory system via the lymphatic ducts located at the junction of the jugular and subclavian veins in the neck.

Lymphatic Capillaries

Lymphatic capillaries , also called the terminal lymphatics, are vessels where interstitial fluid enters the lymphatic system to become lymph fluid. Located in almost every tissue in the body, these vessels are interlaced among the arterioles and venules of the circulatory system in the soft connective tissues of the body (Figure 21.3). Exceptions are the central nervous system, bone marrow, bones, teeth, and the cornea of the eye, which do not contain lymph vessels.

Lymphatic capillaries are formed by a one cell-thick layer of endothelial cells and represent the open end of the system, allowing interstitial fluid to flow into them via overlapping cells (see Figure 21.3). When interstitial pressure is low, the endothelial flaps close to prevent “backflow.” As interstitial pressure increases, the spaces between the cells open up, allowing the fluid to enter. Entry of fluid into lymphatic capillaries is also enabled by the collagen filaments that anchor the capillaries to surrounding structures. As interstitial pressure increases, the filaments pull on the endothelial cell flaps, opening up them even further to allow easy entry of fluid.

In the small intestine, lymphatic capillaries called lacteals are critical for the transport of dietary lipids and lipid-soluble vitamins to the bloodstream. In the small intestine, dietary triglycerides combine with other lipids and proteins, and enter the lacteals to form a milky fluid called chyle . The chyle then travels through the lymphatic system, eventually entering the bloodstream.

Larger Lymphatic Vessels, Trunks, and Ducts

The lymphatic capillaries empty into larger lymphatic vessels, which are similar to veins in terms of their three-tunic structure and the presence of valves. These one-way valves are located fairly close to one another, and each one causes a bulge in the lymphatic vessel, giving the vessels a beaded appearance (see Figure 21.3).

The superficial and deep lymphatics eventually merge to form larger lymphatic vessels known as lymphatic trunks . On the right side of the body, the right sides of the head, thorax, and right upper limb drain lymph fluid into the right subclavian vein via the right lymphatic duct (Figure 21.4). On the left side of the body, the remaining portions of the body drain into the larger thoracic duct, which drains into the left subclavian vein. The thoracic duct itself begins just beneath the diaphragm in the cisterna chyli , a sac-like chamber that receives lymph from the lower abdomen, pelvis, and lower limbs by way of the left and right lumbar trunks and the intestinal trunk.

The overall drainage system of the body is asymmetrical (see Figure 21.4). The right lymphatic duct receives lymph from only the upper right side of the body. The lymph from the rest of the body enters the bloodstream through the thoracic duct via all the remaining lymphatic trunks. In general, lymphatic vessels of the subcutaneous tissues of the skin, that is, the superficial lymphatics, follow the same routes as veins, whereas the deep lymphatic vessels of the viscera generally follow the paths of arteries.

The Organization of Immune Function

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 consist of the following:

  • Barrier defenses such as the skin and mucous membranes, which act instantaneously to prevent pathogenic invasion into the body tissues
  • The rapid but nonspecific innate immune response , which consists of a variety of specialized cells and soluble factors
  • The slower but more specific and effective adaptive immune response , which involves many cell types and soluble factors, but is primarily controlled by white blood cells (leukocytes) known as lymphocytes , which help control immune responses

The cells of the blood, including all those involved in the immune response, arise in the bone marrow via various differentiation pathways from hematopoietic stem cells (Figure 21.5). In contrast with embryonic stem cells, hematopoietic stem cells are present throughout adulthood and allow for the continuous differentiation of blood cells to replace those lost to age or function. These cells can be divided into three classes based on function:

  • Phagocytic cells, which ingest pathogens to destroy them
  • Lymphocytes, which specifically coordinate the activities of adaptive immunity
  • Cells containing cytoplasmic granules, which help mediate immune responses against parasites and intracellular pathogens such as viruses

Lymphocytes: B Cells, T Cells, Plasma Cells, and Natural Killer Cells

As stated above, lymphocytes are the primary cells of adaptive immune responses (Table 21.1). The two basic types of lymphocytes, B cells and T cells, are identical morphologically with a large central nucleus surrounded by a thin layer of cytoplasm. They are distinguished from each other by their surface protein markers as well as by the molecules they secrete. While B cells mature in red bone marrow and T cells mature in the thymus, they both initially develop from bone marrow. T cells migrate from bone marrow to the thymus gland where they further mature. B cells and T cells are found in many parts of the body, circulating in the bloodstream and lymph, and residing in secondary lymphoid organs, including the spleen and lymph nodes, which will be described later in this section. The human body contains approximately 10 12 lymphocytes.

B Cells

B cells are immune cells that function primarily by producing antibodies. An antibody is any of the group of proteins that binds specifically to pathogen-associated molecules known as antigens. An antigen is a chemical structure on the surface of a pathogen that binds to T or B lymphocyte antigen receptors. Once activated by binding to antigen, B cells differentiate into cells that secrete a soluble form of their surface antibodies. These activated B cells are known as plasma cells.

T Cells

The T cell , on the other hand, does not secrete antibody but performs a variety of functions in the adaptive immune response. Different T cell types have the ability to either secrete soluble factors that communicate with other cells of the adaptive immune response or destroy cells infected with intracellular pathogens. The roles of T and B lymphocytes in the adaptive immune response will be discussed further in this chapter.

Plasma Cells

Another type of lymphocyte of importance is the plasma cell. A plasma cell is a B cell that has differentiated in response to antigen binding, and has thereby gained the ability to secrete soluble antibodies. These cells differ in morphology from standard B and T cells in that they contain a large amount of cytoplasm packed with the protein-synthesizing machinery known as rough endoplasmic reticulum.

Natural Killer Cells

A fourth important lymphocyte is the natural killer cell, a participant in the innate immune response. A natural killer cell (NK) is a circulating blood cell that contains cytotoxic (cell-killing) granules in its extensive cytoplasm. It shares this mechanism with the cytotoxic T cells of the adaptive immune response. NK cells are among the body’s first lines of defense against viruses and certain types of cancer.

Type of lymphocyte Primary function
B lymphocyte Generates diverse antibodies
T lymphocyte Secretes chemical messengers
Plasma cell Secretes antibodies
NK cell Destroys virally infected cells

Interactive Link

Visit this website to learn about the many different cell types in the immune system and their very specialized jobs. What is the role of the dendritic cell in an HIV infection?

Primary Lymphoid Organs and Lymphocyte Development

Understanding the differentiation and development of B and T cells is critical to the understanding of the adaptive immune response. It is through this process that the body (ideally) learns to destroy only pathogens and leaves the body’s own cells relatively intact. The primary lymphoid organs are the bone marrow and thymus gland. The lymphoid organs are where lymphocytes mature, proliferate, and are selected, which enables them to attack pathogens without harming the cells of the body.

Bone Marrow

In the embryo, blood cells are made in the yolk sac. As development proceeds, this function is taken over by the spleen, lymph nodes, and liver. Later, the bone marrow takes over most hematopoietic functions, although the final stages of the differentiation of some cells may take place in other organs. The red bone marrow is a loose collection of cells where hematopoiesis occurs, and the yellow bone marrow is a site of energy storage, which consists largely of fat cells (Figure 21.6). The B cell undergoes nearly all of its development in the red bone marrow, whereas the immature T cell, called a thymocyte , leaves the bone marrow and matures largely in the thymus gland.

Thymus

The thymus gland is a bilobed organ found in the space between the sternum and the aorta of the heart (Figure 21.7). Connective tissue holds the lobes closely together but also separates them and forms a capsule.

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The connective tissue capsule further divides the thymus into lobules via extensions called trabeculae. The outer region of the organ is known as the cortex and contains large numbers of thymocytes with some epithelial cells, macrophages, and dendritic cells (two types of phagocytic cells that are derived from monocytes). The cortex is densely packed so it stains more intensely than the rest of the thymus (see Figure 21.7). The medulla, where thymocytes migrate before leaving the thymus, contains a less dense collection of thymocytes, epithelial cells, and dendritic cells.

Aging and the.

Immune System

By the year 2050, 25 percent of the population of the United States will be 60 years of age or older. The CDC estimates that 80 percent of those 60 years and older have one or more chronic disease associated with deficiencies of the immune systems. This loss of immune function with age is called immunosenescence. To treat this growing population, medical professionals must better understand the aging process. One major cause of age-related immune deficiencies is thymic involution, the shrinking of the thymus gland that begins at birth, at a rate of about three percent tissue loss per year, and continues until 35–45 years of age, when the rate declines to about one percent loss per year for the rest of one’s life. At that pace, the total loss of thymic epithelial tissue and thymocytes would occur at about 120 years of age. Thus, this age is a theoretical limit to a healthy human lifespan.

Thymic involution has been observed in all vertebrate species that have a thymus gland. Animal studies have shown that transplanted thymic grafts between inbred strains of mice involuted according to the age of the donor and not of the recipient, implying the process is genetically programmed. There is evidence that the thymic microenvironment, so vital to the development of naïve T cells, loses thymic epithelial cells according to the decreasing expression of the FOXN1 gene with age.

It is also known that thymic involution can be altered by hormone levels. Sex hormones such as estrogen and testosterone enhance involution, and the hormonal changes in pregnant women cause a temporary thymic involution that reverses itself, when the size of the thymus and its hormone levels return to normal, usually after lactation ceases. What does all this tell us? Can we reverse immunosenescence, or at least slow it down? The potential is there for using thymic transplants from younger donors to keep thymic output of naïve T cells high. Gene therapies that target gene expression are also seen as future possibilities. The more we learn through immunosenescence research, the more opportunities there will be to develop therapies, even though these therapies will likely take decades to develop. The ultimate goal is for everyone to live and be healthy longer, but there may be limits to immortality imposed by our genes and hormones.

Secondary Lymphoid Organs and their Roles in Active Immune Responses

Lymphocytes develop and mature in the primary lymphoid organs, but they mount immune responses from the secondary lymphoid organs . A naïve lymphocyte is one that has left the primary organ and entered a secondary lymphoid organ. Naïve lymphocytes are fully functional immunologically, but have yet to encounter an antigen to respond to. In addition to circulating in the blood and lymph, lymphocytes concentrate in secondary lymphoid organs, which include the lymph nodes, spleen, and lymphoid nodules. All of these tissues have many features in common, including the following:

  • The presence of lymphoid follicles, the sites of the formation of lymphocytes, with specific B cell-rich and T cell-rich areas
  • An internal structure of reticular fibers with associated fixed macrophages
  • Germinal centers , which are the sites of rapidly dividing and differentiating B lymphocytes
  • Specialized post-capillary vessels known as high endothelial venules the cells lining these venules are thicker and more columnar than normal endothelial cells, which allow cells from the blood to directly enter these tissues

Lymph Nodes

Lymph nodes function to remove debris and pathogens from the lymph, and are thus sometimes referred to as the “filters of the lymph” (Figure 21.8). Any bacteria that infect the interstitial fluid are taken up by the lymphatic capillaries and transported to a regional lymph node. Dendritic cells and macrophages within this organ internalize and kill many of the pathogens that pass through, thereby removing them from the body. The lymph node is also the site of adaptive immune responses mediated by T cells, B cells, and accessory cells of the adaptive immune system. Like the thymus, the bean-shaped lymph nodes are surrounded by a tough capsule of connective tissue and are separated into compartments by trabeculae, the extensions of the capsule. In addition to the structure provided by the capsule and trabeculae, the structural support of the lymph node is provided by a series of reticular fibers laid down by fibroblasts.

Interactive Link

View the University of Michigan WebScope to explore the tissue sample in greater detail.

The major routes into the lymph node are via afferent lymphatic vessels (see Figure 21.8). Cells and lymph fluid that leave the lymph node may do so by another set of vessels known as the efferent lymphatic vessels . Lymph enters the lymph node via the subcapsular sinus, which is occupied by dendritic cells, macrophages, and reticular fibers. Within the cortex of the lymph node are lymphoid follicles, which consist of germinal centers of rapidly dividing B cells surrounded by a layer of T cells and other accessory cells. As the lymph continues to flow through the node, it enters the medulla, which consists of medullary cords of B cells and plasma cells, and the medullary sinuses where the lymph collects before leaving the node via the efferent lymphatic vessels.

Spleen

In addition to the lymph nodes, the spleen is a major secondary lymphoid organ (Figure 21.9). It is about 12 cm (5 in) long and is attached to the lateral border of the stomach via the gastrosplenic ligament. The spleen is a fragile organ without a strong capsule, and is dark red due to its extensive vascularization. The spleen is sometimes called the “filter of the blood” because of its extensive vascularization and the presence of macrophages and dendritic cells that remove microbes and other materials from the blood, including dying red blood cells. The spleen also functions as the location of immune responses to blood-borne pathogens.

The spleen is also divided by trabeculae of connective tissue, and within each splenic nodule is an area of red pulp, consisting of mostly red blood cells, and white pulp, which resembles the lymphoid follicles of the lymph nodes. Upon entering the spleen, the splenic artery splits into several arterioles (surrounded by white pulp) and eventually into sinusoids. Blood from the capillaries subsequently collects in the venous sinuses and leaves via the splenic vein. The red pulp consists of reticular fibers with fixed macrophages attached, free macrophages, and all of the other cells typical of the blood, including some lymphocytes. The white pulp surrounds a central arteriole and consists of germinal centers of dividing B cells surrounded by T cells and accessory cells, including macrophages and dendritic cells. Thus, the red pulp primarily functions as a filtration system of the blood, using cells of the relatively nonspecific immune response, and white pulp is where adaptive T and B cell responses are mounted.

Lymphoid Nodules

The other lymphoid tissues, the lymphoid nodules , have a simpler architecture than the spleen and lymph nodes in that they consist of a dense cluster of lymphocytes without a surrounding fibrous capsule. These nodules are located in the respiratory and digestive tracts, areas routinely exposed to environmental pathogens.

Tonsils are lymphoid nodules located along the inner surface of the pharynx and are important in developing immunity to oral pathogens (Figure 21.10). The tonsil located at the back of the throat, the pharyngeal tonsil, is sometimes referred to as the adenoid when swollen. Such swelling is an indication of an active immune response to infection. Histologically, tonsils do not contain a complete capsule, and the epithelial layer invaginates deeply into the interior of the tonsil to form tonsillar crypts. These structures, which accumulate all sorts of materials taken into the body through eating and breathing, actually “encourage” pathogens to penetrate deep into the tonsillar tissues where they are acted upon by numerous lymphoid follicles and eliminated. This seems to be the major function of tonsils—to help children’s bodies recognize, destroy, and develop immunity to common environmental pathogens so that they will be protected in their later lives. Tonsils are often removed in those children who have recurring throat infections, especially those involving the palatine tonsils on either side of the throat, whose swelling may interfere with their breathing and/or swallowing.

Interactive Link

View the University of Michigan WebScope to explore the tissue sample in greater detail.

Mucosa-associated lymphoid tissue (MALT) consists of an aggregate of lymphoid follicles directly associated with the mucous membrane epithelia. MALT makes up dome-shaped structures found underlying the mucosa of the gastrointestinal tract, breast tissue, lungs, and eyes. Peyer’s patches, a type of MALT in the small intestine, are especially important for immune responses against ingested substances (Figure 21.11). Peyer’s patches contain specialized endothelial cells called M (or microfold) cells that sample material from the intestinal lumen and transport it to nearby follicles so that adaptive immune responses to potential pathogens can be mounted. A similar process occurs involving MALT in the mucosa and submucosa of the appendix. A blockage of the lumen triggers these cells to elicit an inflammatory response that can lead to appendicitis.

Bronchus-associated lymphoid tissue (BALT) consists of lymphoid follicular structures with an overlying epithelial layer found along the bifurcations of the bronchi, and between bronchi and arteries. They also have the typically less-organized structure of other lymphoid nodules. These tissues, in addition to the tonsils, are effective against inhaled pathogens.

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    What does the lymphatic system do?

    The lymphatic system is part of the immune system. It also maintains fluid balance and plays a role in absorbing fats and fat-soluble nutrients.

    The lymphatic or lymph system involves an extensive network of vessels that passes through almost all our tissues to allow for the movement of a fluid called lymph. Lymph circulates through the body in a similar way to blood.

    There are about 600 lymph nodes in the body. These nodes swell in response to infection, due to a build-up of lymph fluid, bacteria, or other organisms and immune system cells.

    A person with a throat infection, for example, may feel that their “glands” are swollen. Swollen glands can be felt especially under the jaw, in the armpits, or in the groin area. These are, in fact, not glands but lymph nodes.

    They should see a doctor if swelling does not go away, if nodes are hard or rubbery and difficult to move, if there is a fever, unexplained weight-loss, or difficulty breathing or swallowing.

    Share on Pinterest Lymph nodes, or “glands” may swell as the body responds to a threat.

    The lymphatic system has three main functions:

    • It maintains the balance of fluid between the blood and tissues, known as fluid homeostasis.
    • It forms part of the body’s immune system and helps defend against bacteria and other intruders.
    • It facilitates absorption of fats and fat-soluble nutrients in the digestive system.

    The system has special small vessels called lacteals. These enable it to absorb fats and fat-soluble nutrients from the gut.

    They work with the blood capillaries in the folded surface membrane of the small intestine. The blood capillaries absorb other nutrients directly into the bloodstream.

    The lymphatic system consists of lymph vessels, ducts, nodes, and other tissues.

    Around 2 liters of fluid leak from the cardiovascular system into body tissues every day. The lymphatic system is a network of vessels that collect these fluids, or lymph. Lymph is a clear fluid that is derived from blood plasma.

    The lymph vessels form a network of branches that reach most of the body’s tissues. They work in a similar way to the blood vessels. The lymph vessels work with the veins to return fluid from the tissues.

    Unlike blood, the lymphatic fluid is not pumped but squeezed through the vessels when we use our muscles. The properties of the lymph vessel walls and the valves help control the movement of lymph. However, like veins, lymphatic vessels have valves inside them to stop fluid from flowing back in the wrong direction.

    Lymph is drained progressively towards larger vessels until it reaches the two main channels, the lymphatic ducts in our trunk. From there, the filtered lymph fluid returns to the blood in the veins.

    The vessels branch through junctions called lymph nodes. These are often referred to as glands, but they are not true glands as they do not form part of the endocrine system.

    In the lymph nodes, immune cells assess for foreign material, such as bacteria, viruses, or fungus.

    Lymph nodes are not the only lymphatic tissues in the body. The tonsils, spleen, and thymus gland are also lymphatic tissues.

    What do the tonsils do?

    In the back of the mouth, there are tonsils. These produce lymphocytes, a type of white blood cell, and antibodies.

    They have a strategic position, hanging down from a ring forming the junction between the mouth and pharynx. This enables them to protect against inhaled and swallowed foreign bodies. The tonsils are the tissues affected by tonsillitis.

    What is the spleen?

    The spleen is not connected to the lymphatic system in the same way as lymph nodes, but it is lymphoid tissue. This means it plays a role in the production of white blood cells that form part of the immune system.

    Its other major role is to filter the blood to remove microbes and old and damaged red blood cells and platelets.

    The thymus gland

    The thymus gland is a lymphatic organ and an endocrine gland that is found just behind the sternum. It secretes hormones and is crucial in the production, maturation, and differentiation of immune T cells.

    It is active in developing the immune system from before birth and through childhood.

    The bone marrow

    Bone marrow is not lymphatic tissue, but it can be considered part of the lymphatic system because it is here that the B cell lymphocytes of the immune system mature.

    Liver of a fetus

    During gestation, the liver of a fetus is regarded as part of the lymphatic system as it plays a role in lymphocyte development.

    Below is a 3-D model of the lymphatic system, which is fully interactive.

    Explore the model using your mouse pad or touchscreen to understand more about the lymphatic system.

    The lymph system has three main functions.

    Fluid balance

    The lymphatic system helps maintain fluid balance. It returns excess fluid and proteins from the tissues that cannot be returned through the blood vessels.

    The fluid is found in tissue spaces and cavities, in the tiny spaces surrounding cells, known as the interstitial spaces. These are reached by the smallest blood and lymph capillaries.

    Around 90 percent of the plasma that reaches tissues from the arterial blood capillaries is returned by the venous capillaries and back along veins. The remaining 10 percent is drained back by the lymphatics.

    Each day, around 2-3 liters is returned. This fluid includes proteins that are too large to be transported via the blood vessels.

    Loss of the lymphatic system would be fatal within a day. Without the lymphatic system draining excess fluid, our tissues would swell, blood volume would be lost and pressure would increase.

    Absorption

    Most of the fats absorbed from the gastrointestinal tract are taken up in a part of the gut membrane in the small intestine that is specially adapted by the lymphatic system.

    The lymphatic system has tiny lacteals in this part of the intestine that form part of the villi. These finger-like protruding structures are produced by the tiny folds in the absorptive surface of the gut.

    Lacteals absorb fats and fat-soluble vitamins to form a milky white fluid called chyle.

    This fluid contains lymph and emulsified fats, or free fatty acids. It delivers nutrients indirectly when it reaches the venous blood circulation. Blood capillaries take up other nutrients directly.

    The immune system

    The third function is to defend the body against unwanted organisms. Without it, we would die very soon from an infection.

    Our bodies are constantly exposed to potentially hazardous micro-organisms, such as infections.

    The body’s first line of defense involves:

    • physical barriers, such as the skin
    • toxic barriers, such as the acidic contents of the stomach
    • “friendly” bacteria in the body

    However, pathogens often do succeed in entering the body despite these defenses. In this case, the lymphatic system enables our immune system to respond appropriately.

    If the immune system is not able to fight off these micro-organisms, or pathogens, they can be harmful and even fatal.

    A number of different immune cells and special molecules work together to fight off the unwanted pathogens.

    How does the lymphatic system fight infection?

    The lymphatic system produces white blood cells, known as lymphocytes. There are two types of lymphocyte, T cells and B cells. They both travel through the lymphatic system.

    As they reach the lymph nodes, they are filtered and become activated by contact with viruses, bacteria, foreign particles, and so on in the lymph fluid. From this stage, the pathogens, or invaders, are known as antigens.

    As the lymphocytes become activated, they form antibodies and start to defend the body. They can also produce antibodies from memory if they have already encountered the specific pathogen in the past.

    Collections of lymph nodes are concentrated in the neck, armpits, and groin. We become aware of these on one or both sides of the neck when we develop so-called “swollen glands” in response to an illness.

    It is in the lymph nodes that the lymphocytes first encounter the pathogens, communicate with each other, and set off their defensive response.

    Activated lymphocytes then pass further up the lymphatic system so that they can reach the bloodstream. Now, they are equipped to spread the immune response throughout the body, through the blood circulation.

    The lymphatic system and the action of lymphocytes, of which the body has trillions, form part of what immunologists call the “adaptive immune response.” These are highly specific and long-lasting responses to particular pathogens.

    The lymphatic system can stop working properly if nodes, ducts, vessels, or lymph tissues become blocked, infected, inflamed, or cancerous.

    Lymphoma

    Cancer that starts in the lymphatic system is known as lymphoma. It is the most serious lymphatic disease.

    Hodgkin lymphoma affects a specific type of white blood cell known as Reed-Sternberg cells. Non-Hodgkin lymphoma refers to types that do not involve these cells.

    Cancer that affects the lymphatic system is usually a secondary cancer. This means it has spread from a primary tumor, such as the breast, to nearby or regional lymph nodes.

    Lymphadenitis

    Sometimes, a lymph node swells because it becomes infected. The nodes may fill with pus, creating an abscess. The skin over the nodes may be red or streaky.

    Localized lymphadenitis affects the nodes near the infection, for example, as a result of tonsilitis.

    Generalized lymphadenitis can happen when a disease spreads through the bloodstream and affects the whole body. Causes range from sepsis to an upper respiratory tract infection.

    Lymphedema

    If the lymphatic system does not work properly, for example, if there is an obstruction, fluid may not drain effectively. As the fluid builds up, this can lead to swelling, for example in an arm or leg. This is lymphedema.

    The skin may feel tight and hard, and skin problems may occur. In some cases, fluid may leak through the skin.

    Obstruction can result from surgery, radiation therapy, injury, a condition known as lymphatic filariasis, or—rarely—a congenital disorder.

    Why do lymph nodes swell?

    The “swollen glands,” that occur, for example, in the neck during a throat infection, are in fact enlarged lymph nodes.

    Lymph nodes can swell for two common reasons:

    Reaction to an infection: The lymph nodes react when foreign material is presented to immune cells through the lymph that is drained from infected tissue.

    Direct infection of the lymph nodes: The nodes can become infected and inflamed as a result of certain infections that need prompt antibiotic treatment. This is lymphadenitis.

    Most people who have swollen glands with a cold or flu do not need to see a doctor.

    However, medical advice should be sought if:

    • lymph nodes stay swollen for longer than 1 to 2 weeks
    • a swollen lymph node feels hard or fixed in place
    • swelling is accompanied by fever, night sweats, or unexplained weight loss

    Swollen lymph nodes can be symptoms of numerous conditions.

    Glandular fever: Also known as infectious mononucleosis, or mono, this is a viral infection that can one cause longer-lasting swelling, a sore throat , and fatigue.

    Tonsillitis: This is more common in children than in adults. It occurs when the lymph nodes at the back of the mouth are fighting infection, usually viral, but sometimes bacterial.

    Pharyngitis: This bacterial infection is commonly called “strep throat.” It is caused by group A streptococcus bacteria, and it can cause lymph nodes to swell.

    Children are more prone to swollen lymph nodes because their immune systems are still developing their responses to infectious microbes.

    MNT has previously published articles on the following research findings:

    In October 2017, researchers found that the brain has lymphatic vessels, allowing it to process “waste” leaked from the blood vessels. This could provide new insight into the relationship between the brain and the immune system.

    In June 2015, scientists announced that they had discovered a previously unknown lymphatic system that linked it to the central nervous system (CNS) and the brain.

    In May 2015, researchers said that the lymphatic system may play a role in helping the heart to recover after a cardiac arrest.


    Introduction

    In June 1981, the Centers for Disease Control and Prevention (CDC), in Atlanta, Georgia, published a report of an unusual cluster of five patients in Los Angeles, California. All five were diagnosed with a rare pneumonia caused by a fungus called Pneumocystis jirovecii (formerly known as Pneumocystis carinii).

    Why was this unusual? Although commonly found in the lungs of healthy individuals, this fungus is an opportunistic pathogen that causes disease in individuals with suppressed or underdeveloped immune systems. The very young, whose immune systems have yet to mature, and the elderly, whose immune systems have declined with age, are particularly susceptible. The five patients from LA, though, were between 29 and 36 years of age and should have been in the prime of their lives, immunologically speaking. What could be going on?

    A few days later, a cluster of eight cases was reported in New York City, also involving young patients, this time exhibiting a rare form of skin cancer known as Kaposi’s sarcoma. This cancer of the cells that line the blood and lymphatic vessels was previously observed as a relatively innocuous disease of the elderly. The disease that doctors saw in 1981 was frighteningly more severe, with multiple, fast-growing lesions that spread to all parts of the body, including the trunk and face. Could the immune systems of these young patients have been compromised in some way? Indeed, when they were tested, they exhibited extremely low numbers of a specific type of white blood cell in their bloodstreams, indicating that they had somehow lost a major part of the immune system.

    Acquired immune deficiency syndrome, or AIDS, turned out to be a new disease caused by the previously unknown human immunodeficiency virus (HIV). Although nearly 100 percent fatal in those with active HIV infections in the early years, the development of anti-HIV drugs has transformed HIV infection into a chronic, manageable disease and not the certain death sentence it once was. One positive outcome resulting from the emergence of HIV disease was that the public’s attention became focused as never before on the importance of having a functional and healthy immune system.


    As people age, the immune system becomes less effective in the following ways:

    The immune system becomes less able to distinguish self from nonself (that is, to identify foreign antigens). As a result, autoimmune disorders become more common.

    Macrophages (which ingest bacteria and other foreign cells) destroy bacteria, cancer cells, and other antigens more slowly. This slowdown may be one reason that cancer is more common among older people.

    T cells (which remember antigens they have previously encountered) respond less quickly to the antigens.

    There are fewer white blood cells capable of responding to new antigens. Thus, when older people encounter a new antigen, the body is less able to remember and defend against it.

    Older people have smaller amounts of complement proteins and do not produce as many of these proteins as younger people do in response to bacterial infections.

    Although the amount of antibody produced in response to an antigen remains about the same overall, the antibodies become less able to attach to the antigen. This change may partly explain why pneumonia, influenza, infective endocarditis, and tetanus are more common among older people and result in death more often. These changes may also partly explain why vaccines are less effective in older people and thus why it is important for older people to get booster shots (which are available for some vaccines).

    These changes in immune function may contribute to the greater susceptibility of older people to some infections and cancers.


    Autoimmune Responses

    The worst cases of the immune system over-reacting are autoimmune diseases. Somehow, tolerance breaks down and the immune systems in individuals with these diseases begin to attack their own bodies, causing significant damage. The trigger for these diseases is, more often than not, unknown, and the treatments are usually based on resolving the symptoms using immunosuppressive and anti-inflammatory drugs such as steroids. These diseases can be localized and crippling, as in rheumatoid arthritis, or diffuse in the body with multiple symptoms that differ in different individuals, as is the case with systemic lupus erythematosus (Figure 21.6.2).

    Figure 21.6.2 – Autoimmune Disorders: Rheumatoid Arthritis and Lupus. (a) Extensive damage to the right hand of a rheumatoid arthritis sufferer is shown in the x-ray. (b) The diagram shows a variety of possible symptoms of systemic lupus erythematosus.

    Environmental triggers seem to play large roles in autoimmune responses. One explanation for the breakdown of tolerance is that, after certain bacterial infections, an immune response to a component of the bacterium cross-reacts with a self-antigen. This mechanism is seen in rheumatic fever, a result of infection with Streptococcus bacteria, which causes strep throat. The antibodies to this pathogen’s M protein cross-react with an antigenic component of heart myosin, a major contractile protein of the heart that is critical to its normal function. The antibody binds to these molecules and activates complement proteins, causing damage to the heart, especially to the heart valves. On the other hand, some theories propose that having multiple common infectious diseases actually prevents autoimmune responses. The fact that autoimmune diseases are rare in countries that have a high incidence of infectious diseases supports this idea, another example of the hygiene hypothesis discussed earlier in this chapter.

    There are genetic factors in autoimmune diseases as well. Some diseases are associated with the MHC genes that an individual expresses. The reason for this association is likely because if one’s MHC molecules are not able to present a certain self-antigen, then that particular autoimmune disease cannot occur. Overall, there are more than 80 different autoimmune diseases, which are a significant health problem in the elderly. Table 21.7 lists several of the most common autoimmune diseases, the antigens that are targeted, and the segment of the adaptive immune response that causes the damage.

    Autoimmune Diseases (Table 21.7)
    Disease Autoantigen Symptoms
    Celiac disease Tissue transglutaminase Damage to small intestine
    Diabetes mellitus type I Beta cells of pancreas Low insulin production inability to regulate serum glucose
    Graves’ disease Thyroid-stimulating hormone receptor (antibody blocks receptor) Hyperthyroidism
    Hashimoto’s thyroiditis Thyroid-stimulating hormone receptor (antibody mimics hormone and stimulates receptor) Hypothyroidism
    Lupus erythematosus Nuclear DNA and proteins Damage of many body systems
    Myasthenia gravis Acetylcholine receptor in neuromuscular junctions Debilitating muscle weakness
    Rheumatoid arthritis Joint capsule antigens Chronic inflammation of joints

    Chapter Review

    The immune response can be under-reactive or over-reactive. Suppressed immunity can result from inherited genetic defects or by acquiring viruses. Over-reactive immune responses include the hypersensitivities: B cell- and T cell-mediated immune responses designed to control pathogens, but that lead to symptoms or medical complications. The worst cases of over-reactive immune responses are autoimmune diseases, where an individual’s immune system attacks his or her own body because of the breakdown of immunological tolerance. These diseases are more common in the aged, so treating them will be a challenge in the future as the aged population in the world increases.


    Anatomy

    What are the parts of the lymphatic system?

    The lymphatic system consists of many parts. These include:

    • Lymph: Lymph, also called lymphatic fluid, is a collection of the extra fluid that drains from cells and tissues (that is not reabsorbed into the capillaries) plus other substances. The other substances include proteins, minerals, fats, nutrients, damaged cells, cancer cells and foreign invaders (bacteria, viruses, etc). Lymph also transports infection-fighting white blood cells (lymphocytes).
    • Lymph nodes: Lymph nodes are bean-shaped glands that monitor and cleanse the lymph as it filters through them. The nodes filter out the damaged cells and cancer cells. These lymph nodes also produce and store lymphocytes and other immune system cells that attack and destroy bacteria and other harmful substances in the fluid. You have about 600 lymph nodes scattered throughout your body. Some exist as a single node others are closely connected groups called chains. A few of the more familiar locations of lymph nodes are in your armpit, groin and neck. Lymph nodes are connected to others by the lymphatic vessels.·
    • Lymphatic vessels: Lymphatic vessels are the network of capillaries (microvessels) and a large network of tubes located throughout your body that transport lymph away from tissues. Lymphatic vessels collect and filter lymph (at the nodes) as it continues to move toward larger vessels called collecting ducts. These vessels operate very much like your veins do: They work under very low pressure, have a series of valves in them to keep the fluid moving in one direction.
    • Collecting ducts: Lymphatic vessels empty the lymph into the right lymphatic duct and left lymphatic duct (also called the thoracic duct). These ducts connect to the subclavian vein, which returns lymph to your bloodstream. The subclavian vein runs below your collarbone. Returning lymph to the bloodstream helps to maintain normal blood volume and pressure. It also prevents the excess buildup of fluid around the tissues (called edema).

    The lymphatic system collects excess fluid that drains from cells and tissue throughout the body and returns it to the bloodstream, which is then recirculated through the body.

    • Spleen: This largest lymphatic organ is located on your left side under your ribs and above your stomach. The spleen filters and stores blood and produces white blood cells that fight infection or disease.
    • Thymus: This organ is located in the upper chest beneath the breast bone. It matures a specific type of white blood cell that fights off foreign organisms.
    • Tonsils and adenoid: These lymphoid organs trap pathogens from the food you eat and the air you breathe. They are your body’s first line of defense against foreign invaders.
    • Bone marrow: This is the soft, spongy tissue in the center of certain bones, such as the hip bone and breastbone. White blood cells, red blood cells, and platelets are made in the bone marrow.
    • Peyer’s patches: These are small masses of lymphatic tissue in the mucous membrane that lines your small intestine. These lymphoid cells monitor and destroy bacteria in the intestines.
    • Appendix: Your appendix contains lymphoid tissue that can destroy bacteria before it breaches the intestine wall during absorption. Scientists also believe the appendix plays a role in housing “good bacteria” and repopulating our gut with good bacteria after an infection has cleared.

    Modelling the lymphatic system: challenges and opportunities

    The lymphatic system is a vital part of the circulatory and immune systems, and plays an important role in homeostasis by controlling extracellular fluid volume and in combating infection. Nevertheless, there is a notable disparity in terms of research effort expended in relation to the treatment of lymphatic diseases in contrast to the cardiovascular system. While similarities to the cardiovascular system exist, there are considerable differences in their anatomy and physiology. This review outlines some of the challenges and opportunities for those engaged in modelling biological systems. The study of the lymphatic system is still in its infancy, the vast majority of the models presented in the literature to date having been developed since 2003. The number of distinct models and their variants are few in number, and only one effort has been made thus far to study the entire lymphatic network elements of the lymphatic system such as the nodes, which act as pumps and reservoirs, have not been addressed by mathematical models. Clearly, more work will be necessary in combination with experimental verification in order to progress and update the knowledge on the function of the lymphatic system. As our knowledge and understanding of its function increase, new and more effective treatments of lymphatic diseases are bound to emerge.

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    Watch the video: Structure and Immune Function of the Lymphatic System (May 2022).