1.11: Lymphatic and Immune Systems

Learning Objectives

• Apply the rules of medical language to build, analyze, spell, pronounce, abbreviate, and define terms as they relate to the lymph and immune systems
• Identify meanings of key word components of the lymph and immune systems
• Categorize diagnostic, therapeutic, procedural or anatomic terms related to the lymph and immune systems
• Use terms related to the lymph and immune systems
• Use terms related to the diseases and disorders of the lymph and immune systems

Word Parts for the Lymphatic and Immune Systems

Click on prefixes, combining forms, and suffixes to reveal a list of word parts to memorize for the Lymphatic and Immune Systems.

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Introduction to the Lymphatic and Immune Systems

The lymphatic system is a series of vessels, ducts, and trunks that remove interstitial fluid from the tissues and return it the blood. The lymphatic vessels are also used to transport dietary lipids and cells of the immune system. Cells of the immune system, lymphocytes, all come from the hematopoietic system of the bone marrow. Primary lymphoid organs, the bone marrow and thymus gland, are the locations where lymphocytes proliferate and mature. Secondary lymphoid organs are the 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.

This chapter begins by describing the anatomy and physiology of the lymphatic system, whose immune functions lead us into a discussion of the body’s multifaceted defenses, which together make up the immune system. Since the lymphatic system shares organs with a number of other body systems, the pathology discussed near the end of this chapter mainly focuses on disorders of the immune system.

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Lymphatic and Immune Systems Medical Terms

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Anatomy and Physiology 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. 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 (see Figure 11.1). Several organs and tissues that participate in immunity are also part of the lymphatic system.

Figure 11.1 Anatomy of the Lymphatic System. Lymphatic vessels in the arms and legs convey lymph to the larger lymphatic vessels in the torso. From Betts, et al., 2021. Licensed under CC BY 4.0.

Did you know?

Lymphatic vessels and blood vessels are similar in structure and function. Lymph is not actively pumped by the heart, but is forced through the vessels by the movements of the body muscles. (Betts, et al., 2021).

Lymphatic Capillaries

An important function of the lymphatic system is to return the fluid (lymph) to the blood. Lymph may be thought of as recycled blood plasma. Blood pressure causes leakage of fluid from the blood capillaries, resulting in the accumulation of fluid in the interstitial space. In humans, 20 liters of plasma is released into the interstitial space of the tissues each day due to capillary leakage. The blood vessels reabsorb 17 liters of this interstitial fluid, leaving three liters in the tissues for the lymphatic system to transport back to the circulation. If the lymphatic system is damaged in some way, such as by being blocked by cancer cells or destroyed by injury, interstitial fluid accumulates in the tissue spaces, causing a condition called lymphedema.

Lymphatic capillaries, also called the terminal lymphatics, are vessels where interstitial fluid enters the lymphatic system to become lymph. 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. See Figure 11.2. Exceptions are the central nervous system, bone marrow, bones, teeth, and the cornea of the eye, which do not contain lymph vessels.

 

Figure 11.2 Lymphatic Capillaries. Lymphatic capillaries are interlaced with the arterioles and venules of the cardiovascular system. Collagen fibers anchor a lymphatic capillary in the tissue. Interstitial fluid slips through spaces between the overlapping endothelial cells that compose the lymphatic capillary. From CFCF, CC BY-SA 4.0, via Wikimedia Commons

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 11.2).

In general, superficial lymphatics, follow the same routes as veins, whereas deep lymphatic vessels of the viscera generally follow the paths of arteries. The superficial and deep lymphatics eventually merge to form larger lymphatic structures known as lymphatic trunks. On the right side of the body, the right sides of the head, thorax, and right upper limb trunks drain lymph fluid into the right subclavian vein via the right lymphatic duct (see Figure 11.3). On the left side of the body, the trunks from 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.

Figure 11.3 Lymphatic System. (A) The lymphatic system includes the primary and secondary lymphoid organs and a series of lymphatic vessels, providing a one-way drainage route from all tissues back ultimately to the blood circulation via the great veins in the neck. In the primary lymphoid organs (bone marrow and thymus) immune cell production and maturation takes place, whereas secondary lymphoid organs (lymph nodes, spleen, and mucosa associated lymphoid organs such as Peyer’s patch, tonsils, and adenoids) are the sites for lymphocyte activation. (B) The thoracic duct is responsible for the lymph drainage coming from most of the body except for the right sides of the head and neck, the right side of the thorax and the right upper limb that drain primarily into the right lymphatic duct. Both ducts drain into the great veins of the neck. (C) The intricate dermal lymphatic capillary network drains downstream into the lymphatic collector vessels on route to the lymph nodes. (D) Oak leaf-shaped lymphatic capillary cells are connected via discontinuous junctions or buttons allowing the fluid to enter the system passively; the lymphatic collector endothelial cells, on the other hand, present with continuous junctions or zippers. Collectors differ from initial lymphatics by possessing intraluminal valves, smooth muscle cells (SMC) and a continuous basement membrane. Image in (A) is modified from OpenStax College under a CC BY 3.0 license. (C) modified from Open, Learn, Create under a CC BY-NC-SA 4.0 license.

Primary Lymphoid Organs

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
  • Recall that all blood cells, including lymphocytes, are formed in the red bone marrow. 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 thymusgland, where T cells mature, is a bilobed organ found in the space between the sternum and the aorta of the heart (see Figure 11.4). Connective tissue holds the lobes closely together but also separates them and forms a capsule.
  • The loss of immune function with age is called immunosenescence. One major cause of age-related immune deficiencies is thymic involution.
    • The shrinking of the thymus gland begins at birth at a rate of about three percent tissue loss per year. This shrinking continues until 35–45 years of age then 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. So, in theory, 120 years could be the maximum life span.

Figure 11.4 Location and Structure of the Thymus. Modified from Anatomy & Physiology, OpenStax. Licensed under CC BY 3.0, via Wikimedia Commons.

Concept Check

• Do you remember what the suffix “-oid” means?
• Can you explain the term lymphoid?

 

Did You Know?

The thymus gland produces a hormone called thymosin and is therefore also considered to be part of the endocrine system.

Secondary Lymphoid Organs

Figure 11.5 Clonal Selection and Expansion of T Lymphocytes. Stem cells differentiate into T cells with specific receptors, called clones. The clones with receptors specific for antigens on the pathogen are selected for and expanded. From Betts, et al., 2021. Licensed under CC BY 4.0.

Lymphocytes develop and mature in the primary lymphoid organs, but they mount immune responses from the secondary lymphoid organs, which include the lymph nodes, spleen, and lymphoid nodules. A naïve lymphocyteis one that has left the primary organ, where it learned to function immunologically, and entered a secondary lymphoid organ where it waits to encounter an antigen against which it will mount a response.

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” (see Figure 11.6). 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.

Did You Know?

You can live without your spleen. Do you remember the term for “surgical removal of the spleen”?

Spleen

The spleen is a vascular organ that is somewhat fragile due to the absence of a capsule. It is about 12 cm long and is attached to the lateral border of the stomach. 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. (See Fig 11.6).

Figure 11.6 Spleen. The spleen is located in the left side of the abdominal cavity under the diaphragm. It is about the size of a fist and is well supplied with blood. The spleen is the primary filtering element for the blood. From Britannica Encyclopedia (2021). https://www.britannica.com/science/spleen-anatomy

Lymphoid Nodules

The other lymphoid tissues, the lymphoid nodules, 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 (see Figure 11.7). 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. Tonsils have deep grooves called crypts, which accumulate all sorts of materials taken into the body through eating and breathing and actually “encourage” pathogens to penetrate deep into the tonsillar tissues where they are eliminated. A major function of tonsils is 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 children who have recurring throat infections since swollen palatine tonsils can interfere with breathing and/or swallowing.

 

Figure 11.7. Locations of the Tonsils. (a) The pharyngeal tonsil is located on the roof of the posterior superior wall of the nasopharynx. The palatine tonsils lay on each side of the pharynx. Modified From Betts, et al., 2021. Licensed under CC BY 4.0.

Concept Check

Tonsils are named after their locations.

• Look at the figure above and determine which anatomical structure is closely associated with each set of tonsils and was therefore used to name the tonsils, for example, the lingual tonsils are named after the tongue (lingula).
• Can you tell which structures were used to name the palatine tonsils and the pharyngeal tonsils?

 

 

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Media 11.2 Immune System, Part 1: Crash Course A&P #45 [Online video]. Copyright 2015 by CrashCourse.

Cells of the Innate Immune Response

Phagocytes: Macrophages and Neutrophils

A phagocyte is a cell that is able to surround and engulf a particle or cell, a process called phagocytosis. The phagocytes of the immune system engulf other particles or cells, either to clean an area of debris, old cells, or to kill pathogenic organisms such as bacteria. Macrophages, neutrophils, and dendritic cells are the major phagocytes of the immune system and are the body’s fast acting, front line immunological defense against organisms that have breached barrier defenses and have entered the body.

Macrophagesnot only participate in innate immune responses but have also evolved to cooperate with lymphocytes as part of the adaptive immune response. Macrophages exist in many tissues of the body, either freely roaming through connective tissues or fixed to reticular fibers within specific tissues such as lymph nodes. When pathogens breach the body’s barrier defenses, macrophages are the first line of defense.

A neutrophilis a phagocytic cell that is attracted via chemotaxis from the bloodstream to infected tissues. contains cytoplasmic granules, which in turn contain a variety of vasoactive mediators such as histamine. Whereas macrophages act like sentries, always on guard against infection, neutrophils can be thought of as military reinforcements that are called into a battle to hasten the destruction of the enemy.

A monocyteis a circulating precursor cell that differentiates into either a macrophage or dendritic cell, which can be rapidly attracted to areas of infection by signal molecules of inflammation.

Natural Killer Cells

NK cells are a type of lymphocyte that have the ability to induce apoptosis in cells infected with pathogens such as intracellular bacteria and viruses. If apoptosis is induced before the virus has the ability to synthesize and assemble all its components, no infectious virus will be released from the cell, thus preventing further infection.

Concept Check

Do you know the difference between these terms?

• Intercellular
• Intracellular
• Interstitial

Cytokines and Chemokines

A cytokineis signaling molecule that allows cells to communicate with each other over short distances. Cytokines are secreted into the intercellular space, and the action of the cytokine induces the receiving cell to change its physiology. A chemokineis a soluble chemical mediator similar to cytokines except that its function is to attract cells (chemotaxis) from longer distances.

Early Induced Proteins

Early induced proteins are those that are not constitutively present in the body, but are made as they are needed early during the innate immune response. Interferons are an example of early induced proteins. Cells infected with viruses secrete interferons that travel to adjacent cells and induce them to make antiviral proteins. Thus, even though the initial cell is sacrificed, the surrounding cells are protected.

Inflammatory Response

The hallmark of the innate immune response is inflammation. Stub a toe, cut a finger, or do any activity that causes tissue damage and inflammation will result, with its four characteristics: heat, redness, pain, and swelling (“loss of function” is sometimes mentioned as a fifth characteristic). It is important to note that inflammation does not have to be initiated by an infection, but can also be caused by tissue injuries. The release of damaged cellular contents into the site of injury is enough to stimulate the response, even in the absence of breaks in physical barriers that would allow pathogens to enter (by hitting your thumb with a hammer, for example). The inflammatory reaction brings in phagocytic cells to the damaged area to clear cellular debris and encourages the entry of clotting factors to set the stage for wound repair. Inflammation also facilitates the transport of antigen to lymph nodes by dendritic cells for the development of the adaptive immune response. (Fig. 11.8).

 

Figure 11.8 Inflammatory Response. From Betts, et al., 2021. Licensed under CC BY 4.0.

The above image summarizes the following events in the inflammatory response:

• • The released contents of injured cells stimulate the release of substances from mast cells including histamine, leukotrienes, and prostaglandins.

• • Histamine increases blood flow to the area by vasodilation, resulting in heat and redness. Histamine also increases the permeability of local capillaries, causing plasma to leak out and form interstitial fluid, resulting in swelling

• • Leukotrienes attract neutrophils from the blood by chemotaxis.
    When local infections are severe, neutrophils are attracted to the sites of infections in large numbers, and as they phagocytose the pathogens and subsequently die, their accumulated cellular remains are visible as pus at the infection site.

• • Prostaglandins cause vasodilation by relaxing vascular smooth muscle and are a major cause of the pain associated with inflammation. Nonsteroidal anti-inflammatory drugs such as aspirin and ibuprofen relieve pain by inhibiting prostaglandin production.

Concept Check

• Do you remember the suffix used to describe ‘inflammation’?
• Describe what causes the pain associated with inflammation.

Acute inflammation is a short-term innate immune response to an insult to the body. If the cause of the inflammation is not resolved, however, it can lead to chronic inflammation, which is associated with major tissue destruction and fibrosis.

Phase 3: Adaptive Immune Response

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Media 11.3 Immune System, Part 2: Crash Course A&P #46 [Online video]. Copyright 2015 by CrashCourse.

Benefits of the Adaptive Immune Response

• Specificity
  • The ability to specifically recognize and mount a response against almost any pathogen.
  • Antigens, are recognized by receptors on the surface of B and T lymphocytes.

•  
• Immunological Memory
  • The first exposure to a pathogen is called a primary adaptive response.
  • Symptoms of a first infection, called primary disease, are always relatively severe because it takes time for an initial adaptive immune response to a pathogen to become effective.
  • Upon re-exposure to the same pathogen, a secondary adaptive immune responseis generated, which is stronger and faster that the primary response, often eliminating the pathogen before it can cause damage or even symptoms.
  • This secondary response is the basis of immunological memory, which gives us immunity.

Figure 11.9 Primary and Secondary Antibody Responses. Antigen A is given once to generate a primary response and later to generate a secondary response. When a different antigen is given for the first time, a new primary response is made. From Betts, et al., 2021. Licensed under CC BY 4.0.

• Self Recognition
  • The ability to distinguish between self-antigens, those that are normally present in the body, and foreign antigens, those that might be on a potential pathogen.
  • As T and B cells mature, there are mechanisms in place that prevent them from recognizing self-antigen, preventing a damaging immune response against the body. When these mechanisms fail, their breakdown leads to autoimmune diseases.

Lymphocytes: B Cells, T Cells, Plasma Cells

As stated above, lymphocytes are the primary cells of adaptive immune responses. These cells were introduced in the previous chapter and are summarized in the following table:

Table 11.1 Cells of the Adaptive Immune Response. From Betts, et al., 2021. Licensed under CC BY 4.0.

CELL TYPE	DESCRIPTION AND DETAILS
Plasma Cell	B cell (lymphocyte) that has been activated through exposure to an antigen and produces antibodies against that antigen (see the figure below) There are 5 classes of antibodies (IgM, IgG, IgE, IgA, IgD), each functioning in different ways: IgM promotes chemotaxis, opsonization, and cell lysis, making it a very effective antibody against bacteria at early stages of a primary antibody response IgG is the one that crosses the placenta to protect the developing fetus from disease and exits the blood to the interstitial fluid to fight extracellular pathogens IgA is the only antibody to leave the interior of the body to protect body surfaces. IgA is also of importance to newborns, because this antibody is present in mother’s breast milk (colostrum), which serves to protect the infant IgE is associated with allergies and anaphylaxis
T Cell	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 pathogen Cytotoxic T Cell (Tc) kill target cells by inducing apoptosis using the same mechanism as NK cells: killing a virally infected cell before the virus can complete its replication cycle results in the production of no infectious particles Helper T Cell (Th) release cytokines, which help to develop and regulate other immune system cells Suppressor T Cell (also called regulatory T cell) control T Cell response, in order to prevent too many T cells from being formed during an immune repsonse
Memory Cell	B cells and T cells formed during primary exposure to a pathogen (see the figure below) Remain in the body for a long time after an infection and are able to mount a fast and effective immune response to a pathogen if it is encountered a second time, preventing the pathogen from causing disease

 

Figure 11.10 Clonal Selection of B Cells. During a primary B cell immune response, both antibody-secreting plasma cells and memory B cells are produced. These memory cells lead to the differentiation of more plasma cells and memory B cells during secondary responses. From Betts, et al., 2021. Licensed under CC BY 4.0.

Active Versus Passive Immunity

Immunity to pathogens, and the ability to control pathogen growth so that damage to the tissues of the body is limited, can be acquired by:

1. The active development of an immune response in the infected individual.
   or
2. The passive transfer of immune components from an immune individual to a non-immune one.

The downside to this passive immunity is the lack of the development of immunological memory. Once the antibodies are transferred, they are effective for only a limited time before they degrade.

Table 11.2 Active Versus Passive Immunity. From Betts, et al., 2021. Licensed under CC BY 4.0.

IMMUNITY	NATURAL	ARTIFICIAL
Active: resistance to pathogens acquired during an adaptive immune response	Result of memory cells formed during the adaptive immune response to a pathogen	Vaccine response. Through vaccination, one avoids the disease that results from the first exposure to the pathogen, yet reaps the benefits of protection from immunological memory. Vaccination was one of the major medical advances of the twentieth century and led to the eradication of smallpox and the control of many infectious diseases, including polio, measles, and whooping cough
Passive: transfer of antibodies from an immune person to a nonimmune person	Trans-placental antibodies from mother to fetus and maternal antibodies in breast milk protect newborn from infections	Immunoglobulin injections taken from animals previously exposed to a specific pathogen; a fast-acting method of temporarily protecting an individual who was possibly exposed to a pathogen

Evasion of the Immune System by Pathogens

The immune system and pathogens are in a slow, evolutionary race to see who stays on top. Early childhood is a time when the body develops much of its immunological memory that protects it from diseases in adulthood. Pathogens have shown the ability, however, to evade the body’s immune responses, as described below.

• • Protective adaptations: It is important to keep in mind that although the immune system has evolved to be able to control many pathogens, pathogens themselves have evolved ways to evade the immune response. An example is in Mycobactrium tuberculosis, which has evolved a complex cell wall that is resistant to the digestive enzymes of the macrophages that ingest them, and thus persists in the host, causing the chronic disease tuberculosis.

• • Multiple strains: Bacteria sometimes evade immune responses because they exist in multiple strains, each having different surface antigens and requiring individual adaptive immune responses. One example is a small group of strains of S. aureus, called methicillin-resistant Staphylococcus aureus (MRSA), which has become resistant to multiple antibiotics..

• • Antigen mutation: Because viruses’ surface molecules mutate continuously, viruses like influenza change enough each year that the flu vaccine for one year may not protect against the flu common to the next. New vaccine formulations must be derived for each flu season.

• • Genetic recombination: An example is the influenza virus, which contains gene segments that can recombine when two different viruses infect the same cell. Recombination between human and pig influenza viruses led to the 2010 H1N1 swine flu outbreak.

• • Immunosuppression: Pathogens, especially viruses, can produce immunosuppressive molecules that impair immune function.

Tissue Transplantation

With the use of tissue typing and anti-rejection drugs, transplantation of organs and the control of the anti-transplant immune response have made huge strides in the past 50 years.

Immunosuppressive drugs such as cyclosporine A have made transplants more successful, but tissue matching is still key. Family members, since they share a similar genetic background, are much more likely to share MHC molecules than unrelated individuals do.

One disease of transplantation occurs with bone marrow transplants, which are used to treat various diseases, including SCID and leukemia. Because the bone marrow cells being transplanted contain lymphocytes capable of mounting an immune response, and because the recipient’s immune response has been destroyed before receiving the transplant, the donor cells may attack the recipient tissues, causing graft-versus-host disease. Symptoms of this disease, which usually include a rash and damage to the liver and mucosa, are variable, and attempts have been made to moderate the disease by first removing mature T cells from the donor bone marrow before transplanting it.

Immune Responses Against Cancer

It is clear that with some cancers, like Kaposi’s sarcoma (see Figure 11.11), for example, that a healthy immune system does a good job at controlling them. This disease, which is caused by the human herpes virus, is almost never observed in individuals with strong immune systems. Other examples of cancers caused by viruses include liver cancer caused by the hepatitis B virus and cervical cancer caused by the human papilloma virus. As these last two viruses have vaccines available for them, getting vaccinated can help prevent these two types of cancer by stimulating the immune response.

Figure 11.11 Kaposi’s Sarcoma Lesions. (credit: National Cancer Institute). From Betts, et al., 2021. Licensed under CC BY 4.0.

On the other hand, as cancer cells are often able to divide and mutate rapidly, they may escape the immune response, just as certain pathogens such as HIV do.

There are three stages in the immune response to many cancers:

1. 1. Elimination occurs when the immune response first develops toward tumor-specific antigens specific to the cancer and actively kills most cancer cells.
   2. Equilibrium is the period that follows, during which the remaining cancer cells are held in check.
   3. Escape of the immune response, and resulting disease, occurs because many cancers mutate and no longer express any specific antigens for the immune system to respond to.

1.  

This fact has led to extensive research in trying to develop ways to enhance the early immune response to completely eliminate the early cancer and thus prevent a later escape. One method that has shown some success is the use of cancer vaccines. These differ from other vaccines in that they are directed against the cells of one’s own body. Treated cancer cells are injected into cancer patients to enhance their anti-cancer immune response and thereby prolong survival. The immune system has the capability to detect these cancer cells and proliferate faster than the cancer cells do, thus overwhelming the cancer in a similar way as they do for viruses. Cancer vaccines are being developed for malignant melanoma and renal (kidney) cell carcinoma.

Immune Responses and Stress

In order to protect the entire body from infection, the immune system is required to interact with other organ systems, sometimes in complex ways. For example, hormones such as cortisol (naturally produced by the adrenal cortex) and prednisone (synthetic) are well known for their abilities to suppress T cell immune mechanisms, hence, their prominent use in medicine as long-term, anti-inflammatory drugs.

One well-established interaction of the immune, nervous, and endocrine systems is the effect of stress on immune health. In the human vertebrate evolutionary past, stress was associated with the fight-or-flight response, largely mediated by the central nervous system and the adrenal medulla. This stress was necessary for survival since fighting or fleeing usually resolved the problem in one way or another. It has been found that short-term stress diverts the body’s resources towards enhancing innate immune responses. This has the ability to act fast and would seem to help the body prepare better for possible infections associated with the trauma that may result from a fight-or-flight exchange.

On the other hand, there are no physical actions to resolve most modern day stresses, including short-term stressors like taking examinations and long-term stressors such as being unemployed or losing a spouse. The effect of stress can be felt by nearly every organ system, and the immune system is no exception (see Table 11.3). Chronic stress, unlike short-term stress, may inhibit immune responses even in otherwise healthy adults. The suppression of both innate and adaptive immune responses is clearly associated with increases in some diseases.

Table 11.3 Effects of Stress on Body Systems. From Betts, et al., 2021. Licensed under CC BY 4.0.

SYSTEM	STRESS-RELATED ILLNESS
Integumentary system	Acne, skin rashes, irritation
Nervous system	Headaches, depression, anxiety, irritability, loss of appetite, lack of motivation, reduced mental performance
Muscular and skeletal systems	Muscle and joint pain, neck and shoulder pain
Circulatory system	Increased heart rate, hypertension, increased probability of heart attacks
Digestive system	Indigestion, heartburn, stomach pain, nausea, diarrhea, constipation, weight gain or loss
Immune system	Depressed ability to fight infections
Male reproductive system	Lowered sperm production, impotence, reduced sexual desire
Female reproductive system	Irregular menstrual cycle, reduced sexual desire

Anatomy Labeling Activity

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Medical Terms not Easily Broken into Word Parts

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Lymphatic and Immune System Abbreviations

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Diseases and Disorders of the Lymphatic and Immune Systems

The immune response can be under-reactive or over-reactive, leading to a state of disease. The factors that maintain immunological homeostasis are complex and incompletely understood.

Underactive Immune System: Immunodeficiencies

Suppressed immunity can result from inherited genetic defects or by acquiring viruses (Betts, et al., 2021).

Inherited Immunodeficiencies/SCID

While many inherited immunodeficiencies exist, the most serious is severe combined immunodeficiency disease (SCID). This complex disease is caused by many different genetic defects which result in impaired B cell and T cell arms of the adaptive immune response. Children with this disease usually die of opportunistic infections within their first year of life unless they receive a bone marrow transplant. Such a procedure had not yet been perfected for David Vetter, the “boy in the bubble,” who was treated for SCID by having to live in a sterile plastic cocoon for the 12 years before his death from infection in 1984. One of the features that make bone marrow transplants work as well as they do is the proliferative capability of hematopoietic stem cells of the bone marrow. Only a small amount of bone marrow from a healthy donor is given intravenously to the recipient. It finds its own way to the bone where it populates it, eventually reconstituting the patient’s immune system, which is usually destroyed beforehand by treatment with radiation or chemotherapeutic drugs (Betts, et al., 2021).

New treatments for SCID using gene therapy, inserting nondefective genes into cells taken from the patient and giving them back, have the advantage of not needing the tissue match required for standard transplants. Although not a standard treatment, this approach holds promise, especially for those in whom standard bone marrow transplantation has failed (Betts, et al., 2021).

Acquired Immunodeficiency/HIV and AIDS

Although many viruses cause suppression of the immune system, only HIV wipes it out completely. HIV is transmitted through semen, vaginal fluids, and blood, and can be caught by risky sexual behaviors and the sharing of needles by intravenous drug users. There are sometimes, but not always, flu-like symptoms in the first 1 to 2 weeks after infection. The presence of anti-HIV antibodies indicates a positive HIV test. Because seroconversion takes different lengths of time in different individuals, multiple HIV tests are given months apart to confirm or eliminate the possibility of infection.

After seroconversion, the amount of virus circulating in the blood drops and stays at a low level for several years. During this time, the levels of CD4 T cells decline steadily, until at some point, the immune response is so weak that opportunistic disease and eventually death result.

Treatment for the disease consists of drugs that target virally encoded proteins that are necessary for viral replication but are absent from normal human cells. By targeting the virus itself and sparing the cells, this approach has been successful in significantly prolonging the lives of HIV-positive individuals (Betts, et al., 2021).

Overactive Immune System: Hypersensitivities and Autoimmune Diseases

Hypersensitivities

Over-reactive immune responses include the hypersensitivities: allergies and inflammatory responses to nonpathogenic environmental substances (Betts, et al., 2021). The table below compares different hypersensitivities.

Table 11.4 Table Summarizing Types of Hypersensitivities. From Betts, et al., 2021. Licensed under CC BY 4.0.

TYPE OF HYPERSENSITIVITY	DETAILS AND EXPLANATION
Type I	Allergies and allergic asthma Major symptoms of inhaled allergens are the nasal edema and runny nose caused by the increased vascular permeability and increased blood flow of nasal blood vessels ‘Immediate Hypersensitivity’: usually rapid and occur within just a few minutes Mild allergies are usually treated with antihistamines Severe allergies that may cause anaphylactic shock, which can be fatal within 20 to 30 minutes if untreated; epinephrine raises blood pressure and relaxes bronchial smooth muscle and is routinely used to counteract the effects of anaphylactic shock
Type II	Occurs during mismatched blood transfusions and blood compatibility diseases such as erythroblastosis fetalis
Type III	Occurs with diseases such as systemic lupus erythematosus
Type IV	‘Delayed hypersensitivity’-takes 24-72 hours to develop A standard cellular immune response in which the first exposure to an antigen is called sensitization, such that on re-exposure, an immune response results The classical test for delayed hypersensitivity is the tuberculin test for tuberculosis, where bacterial proteins from M. tuberculosis are injected into the skin. A couple of days later, a positive test, as indicated by an induration, means that the patient has been exposed to the bacteria and exhibits a cellular immune response to it Another type of delayed hypersensitivity is contact sensitivity, where substances such as the metal nickel cause a red and swollen area upon contact with the skin in an individual who was previously sensitized to the metal.

Autoimmune Responses

The worst cases of the immune system over-reacting are autoimmune diseases in which the immune systems begin to attack cells of the patient’s own body, causing chronic inflammation and significant damage. The trigger for these diseases is often unknown, although environmental and genetic factors are likely involved. Treatments are usually based on resolving the symptoms using immunosuppressive and anti-inflammatory drugs. Figure 11.12 below provides two examples of autoimmune diseases: rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) (Betts, et al., 2021).

Figure 11.12 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. From Betts, et al., 2021. Licensed under CC BY 4.0.

Overall, there are more than 80 different autoimmune diseases, which are a significant health problem in the elderly. Table 14.5 below lists several of the most common autoimmune diseases, the antigens that are targeted (autoantigen or “self” antigen), and the resulting tissue damage (Betts, et al., 2021).

Table 11.5 Autoimmune Diseases. From Betts, et al., 2021. Licensed under CC BY 4.0.

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

Lymphoma

Lymphoma was briefly discussed in the previous chapter.

Medical Terms in Context

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Medical Specialties and Procedures Related to the Lymphatic and Immune Systems

Clinical Immunology/Allergy is a medical specialty that diagnoses and treats diseases of the immune system (American Academy of Allergy Asthma and Immunology, 2021). For more information, please visit the ‘About Careers in Allergy/Immunology‘ page from the American Academy of Allergy Asthma and Immunology.

Skin testing (for allergies) is done by a clinical immunologist/allergist to identify allergens in Type I hypersensitivity. In skin testing, allergen extracts are injected into the epidermis, and a positive result of the wheal and flare response usually occurs within 30 minutes. The soft center is due to fluid leaking from the blood vessels and the redness is caused by the increased blood flow to the area that results from the dilation of local blood vessels at the site (Betts, et al., 2021).

Test Yourself

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References

American Academy of Allergy Asthma and Immunology. (2021). About Careers in Allergy/Immunology. https://www.aaaai.org/Professional-Education/careers-in-a-i

[CrashCourse]. (2015, November 30). Lymphatic system: Crash course A&P #44 [Video]. YouTube. https://youtu.be/I7orwMgTQ5I

[CrashCourse]. (2015, December 8). Immune system, part 1: Crash course A&P #45 [Video]. YouTube. https://youtu.be/GIJK3dwCWCw

[CrashCourse]. (2015, December 14). Immune system, part 2: Crash course A&P #46 [Video]. YouTube. https://youtu.be/2DFN4IBZ3rI

Unless otherwise indicated, this chapter contains material adapted from Anatomy and Physiology (on OpenStax), by Betts, et al. and is used under a a CC BY 4.0 international license. Download and access this book for free at https://openstax.org/books/anatomy-and-physiology/pages/1-introduction.