42.1. Lymphatic System Helps Circulatory System (p. 756)
A. Lymphatic System Characteristics
1. The mammalian lymphatic system consists of lymphatic vessels and lymphoid organs.
2. Closely associated with the cardiovascular system, it has three main functions.
a. Lymphatic vessels take up excess tissue fluid and return it to the bloodstream.
b. Lymphatic capillaries absorb fats at intestinal villi and lymphatic vessels transport fats to the bloodstream.
c. The lymphatic system helps to defend the body against disease.
B. Lymphatic Vessels Transport One Way
1. Lymphatic vessels are extensive; most regions have supply of lymphatic capillaries. (Fig. 42.1) [transp. 228]
2. The structure of larger lymphatic vessels resembles veins, including valves. (Fig. 42.1) [transp. 228]
3. Movement of fluid through these vessels is dependent upon skeletal muscle contraction; when muscles contract, fluid is squeezed past a valve that closes, preventing the fluid from flowing backwards.
4. The lymphatic system is a one-way system that begins with lymphatic capillaries, which take up fluid that has diffused from but has not been reabsorbed by the blood capillaries.
a. If excess tissue fluid is not absorbed, but instead accumulates, edema will result.
b. Edema is swelling caused by buildup of fluid from excessive production or inadequate drainage.
5. Once tissue fluid enters lymphatic capillaries, it is called lymph.
6. Lymphatic capillaries join as lymphatic vessels that merge before entering one of two lymphatic ducts.
a. The thoracic duct is larger than the right lymphatic duct; serves lower extremities, abdomen, left arm, left side of head and neck, and left thoracic region; delivers lymph to left subclavian vein of cardiovascular system.
b. The right lymphatic duct is smaller; serves right arm, right side of head and neck, and right thoracic region; delivers lymph to the right subclavian vein of the cardiovascular system.
C. Lymphoid Organs Assist Immunity [transp. 229]
1. Lymphoid organs include lymph nodes, spleen, thymus gland, and bone marrow. (Figs. 42.1 and 42.2) [transp. 228]
2. Lymph nodes are small (about 1-25 mm) ovoid or round masses of lymphoid tissue located along the course of lymphatic vessels.
3. A lymph node has a fibrous connective tissue capsule penetrated by incoming and outgoing lymphatic vessels.
4. Connective tissue divides a lymph node into nodules filled with numerous lymphocytes and macrophages.
5. As lymph passes through the sinuses, the macrophages phagocytize infectious organisms and any other debris.
6. Nodules can occur singly or in groups.
a. Tonsils are located at the back of the mouth to either side.
b. Adenoids are on the posterior wall above the border of the soft palate.
c. Peyer's patches are found within the intestinal wall.
7. Lymph nodes cluster in certain regions of the body (e.g., in groin and armpits). [transp. 228]
8. Spleen is located in upper left abdominal cavity just below diaphragm. [transp. 228, 229]
a. Construction of the spleen is similar to that of a lymph node.
b. Outer connective tissue divides the spleen into lobules which contain sinuses filled blood instead of lymph.
c. Blood vessels of the spleen expand, increasing capacity to serve as a blood reservoir and to make blood available under conditions of low blood pressure or when body needs extra oxygen carrying capacity.
d. A spleen nodule contains the following:
1) red pulp that contains red blood cells, lymphocytes, and macrophages; helps to purify the blood that passes through the spleen by removing microorganisms and worn-out or damaged red blood cells.
2) white pulp that contains mostly lymphocytes.
e. If the spleen ruptures due to injury, it can be removed, and its functions are assumed by other organs.
f. A person whose spleen is removed is more susceptible to infections; may require antibiotic therapy.
9. Thymus gland is located along trachea behind sternum in upper thoracic cavity. [transp. 228, 229]
a. The thymus gland tends to be larger in children than in adults and may disappear completely in old age.
b. It is divided into lobules by connective tissue; the lobules are the site of T lymphocyte maturation.
c. The interior (medulla) of each lobule consists mostly of epithelial cells, which produce and secrete thymic hormones (e.g., thymosin), that are thought to promote maturation of T lymphocytes.
10. Red bone marrow is the site of origination for all types of blood cells, including the five types of leukocytes that function in immunity. (Fig. 42.3) [micro. slides 89-93]
a. Red bone marrow contains stem cells, continually producing cells that differentiate into various blood cells.
b. Most bones of a child have red bone marrow; in adults it is only in skull, sternum, ribs, clavicle, pelvic bones and vertebral column.
c. Red bone marrow consists of a reticular lymphoid tissue produced by reticular cells packed in thin-walled sinuses.
d. Differentiated blood cells enter the venous portion of the cardiovascular system from the bone sinuses.
42.2. Some Defenses Are Nonspecific (p. 758)
A. Immunity is ability of the body to defend against infectious agents, foreign cells, and abnormal cancer cells.
1. Immunity includes nonspecific and specific defenses.
2. Three nonspecific defenses include barrier to entry, the inflammatory reaction, and protective proteins.
B. Barring Entry
1. Skin and mucous membranes lining the respiratory, digestive, and urinary tracts serve as mechanical barriers.
2. Oil gland secretions inhibit the growth of bacteria on the skin.
3. Respiratory tract is lined by ciliated cells to sweep mucous and particles up into throat to be swallowed.
4. The stomach has a low pH (1.2-3.0) that inhibits growth of many types of bacteria.
5. Various bacteria that normally reside in the intestine or the vagina prevent pathogens from colonizing.
C. Inflammatory Reaction
1. If skin is broken, a series of events occurs known as the inflammatory reaction. (Fig. 42.4)
[transp. 230]
2. The inflamed area has four symptoms: redness, pain, swelling, and heat.
3. When tissue damage occurs, a capillary and several tissue cells are apt to rupture and release bradykinin.
a. Bradykinin triggers nerve impulses in pain receptors and stimulates mast cells to release histamine.
b. Bradykinin and histamine cause vasodilation and increased permeability of capillaries.
c. Enlarged capillaries produce redness and local increase in temperature.
d. A rise in local temperature reduces invading pathogens and increases phagocytosis by WBCs.
4. Chemicals released by damaged tissue cause neutrophils and monocytes to migrate by amoeboid movement to the site of injury, where they escape from the blood by squeezing through the capillary wall.
5. When monocytes enter tissue, they differentiate into macrophages that ingest hundreds of bacteria or viruses.
6. Connective and lymphoid tissues have resident macrophages that devour old blood cells and cellular debris.
7. Macrophages trigger an explosive increase in leukocytes by releasing a growth factor; this hormone diffuses into blood and is transported to red bone marrow to stimulate production of WBCs, especially neutrophils.
8. Pus is the accumulation of dead neutrophils along with tissue, cells, bacteria and, living WBCs.
D. Protective Proteins
1. The complement system, called complement, is plasma proteins designated by letter C and a subscript.
a. Once complement protein is activated, it activates another protein in a set series of domino reactions.
b. Therefore, a limited amount of protein can activate many other proteins.
c. Complement is activated when microbes enter the body.
d. It "complements" certain immune responses, which accounts for its name.
e. Complement amplifies the inflammatory reaction by attracting phagocytic cells to the site of infection.
f. Complement binds to antibodies already on the surface of the microbes, thereby increasing the probability that the microbes will be phagocytized by a neutrophil or macrophage. This facilitated phagocytosis is called opsonization.
g. Certain activated complement proteins can result in a membrane attack complex that produces holes in bacterial cell walls and plasma membranes; as potassium ions leave, fluids and salts enter bacteria to a point where they burst. (Fig. 42.5)
2. Interferon is a protein produced by virus-infected animal cells.
a. It binds to receptors of noninfected cells, producing substances that interfere with viral replication.
b. Interferon is specific to the species; only human interferon can be used in humans.
c. Interferon is now produced in quantity by recombinant DNA technology.
42.3. Other Defenses Are Specific (p. 760)
A. Sometimes specific defenses are required against a particular antigen.
1. Antigens are protein, or polysaccharide, that stimulates immune system to react.
2. Foreign cells, including microorganisms, have antigens, and antigens can also be components of cancer cells.
3. Because we do not ordinarily become immune to our own cells, the immune system can tell self from nonself.
4. Immunity usually lasts for some time; we do not ordinarily get the same illness a second time.
B. Specific immunity is primarily the result of the action of B lymphocytes and T lymphocytes.
1. B lymphocytes give rise to plasma cells that produce antibodies.
2. Antibodies are large globular proteins that combine with and neutralize antigens.
3. Antibodies are secreted into the blood and lymph.
4. T lymphocytes either directly attack cells that bear antigens or regulate the immune response.
5. B lymphocytes mature in the bone marrow; T lymphocytes mature in the thymus.
6. Lymphocytes are capable of recognizing an antigen; they have receptor molecules on the plasma membranes.
a. The receptor-antigen fit is compared to a lock and key.
b. During our lifetime, we encounter a million different antigens; we need the same number of lymphocytes.
c. During maturation process, diversification produces a different lymphocyte for each possible antigen.
d. Despite this diversity, none of the lymphocytes attacks the body's own proteins.
C. B Cells Make Plasma Cells and Memory Cells
1. Each type of B cell carries its specific antibody, as a membrane-bound receptor, on its surface.
2. When a B cell in a lymph node or spleen encounters an appropriate antigen, it becomes activated to divide.
3. Most of resulting cells are plasma cells; a mature B cell that mass-produces antibodies in the blood or lymph.
4. Clonal selection theory states that the antigen selects which B cell will produce a clone of plasma cells. (Fig. 42.6) [transp. 231]
5. A B cell will not clone until its antigen is present; it can recognize antigen directly.
6. However, B cells are stimulated to clone by helper T cells.
7. Once antibody production is sufficient to agglutinate and/or neutralize the amount of antigen present in the system, the development of plasma cells ceases.
8. Cloned B cells that do not participate in antibody production remain in blood as memory B cells.
9. Memory B cells provide long-term immunity; if the same antigen enters system again, memory B cells bind to antigen, quickly divide and give rise to many new plasma cells which produce large amounts of antibody.
10. B cells are responsible for antibody-mediated immunity.
11. It is also called humoral immunity because antibodies are present it blood; a humor is a body fluid.
D. How Antibodies Work
1. The most common antibody (IgG) is a Y-shaped molecule with two arms.
2. Each arm has both a "heavy" and "light" polypeptide chain of amino acids. (Fig. 42.7) [transp. 232]
a. These chains have constant regions and variable regions.
b. Constant regions have amino acid sequences that do not change; not identical among all antibodies.
c. Variable regions have portions of the polypeptide chains whose amino acid sequence does change, providing antigen specificity; forms antigen binding sites of antibodies; their shape is specific to antigen.
3. An antigen binds with a specific antibody at the antigen-binding site in a lock-and-key manner.
4. Antigen-antibody complex (or immune complex) marks antigen for destruction by other mechanisms (e.g., neutrophils or macrophages) or it may activate complement.
5. If complement attaches to antigens on the surface of microbes, it renders microbes more easily phagocytized.
E. How Antibodies Differ
1. There are five different classes of circulating antibodies. (Table 42.1)
2. IgG antibodies are major type in blood; lesser amounts are found in lymph; IgG attacks bacteria and toxins.
3. IgM antibodies contain five Y-shaped structures; they appear in blood soon after an infection begins and disappear before it is over; they are good activators of the complement system.
4. IgA antibodies contain two Y-shaped structures; they attack microbes and toxins before they reach the blood.
5. The role of IgD antibodies is uncertain; a limited number is in the blood.
6. IgE antibodies are responsible for allergic reactions.
F. T Cells Become Cytotoxic, Helper, Memory, or Suppressor Cells
1. Cytotoxic and helper T cells differentiate in the thymus; memory and suppressor T cells arise at a later time.
2. All types of T cells look alike but are distinguished by their functions.
3. Some doubt the existence of suppressor T cells and attribute suppression to cytokines released by T cells.
4. Cytotoxic T cells are sometimes called killer T cells. (Fig. 42.8) [micro. slide 94]
a. They attack and destroy antigen-bearing cells (e.g., virus-infected or cancer cells).
b. They have storage vacuoles that contain perforin molecules.
c. Perforin molecules perforate a plasma membrane; allow water and salts to enter, causing cell to burst.
d. Only cytotoxic T cells are responsible for cell-mediated immunity.
5. Helper T cells regulate immunity by improving the response of other immune cells.
a. When exposed to an antigen, they enlarge and secrete lymphokines.
b. Lymphokines stimulate the helper T cells to clone and other immune cells to perform their functions.
1) Lymphokines stimulate macrophages to phagocytize.
2) They stimulate B cells to become antibody-producing plasma cells.
c. HIV (causes AIDS) infects primarily helper T cells and inactivates the immune response (see p. 766).
6. Suppressor T cells regulate the immune response by suppressing further development of helper T cells.
a. Since helper T cells also stimulate antibody production by B cells, suppressor T cells help prevent the B cell and T cell immune response from getting out of control.
b. Following suppression, a population of memory T cells persists, perhaps for life.
7. Memory T cells secrete lymphokines and by stimulating macrophages and B cells whenever the same antigen reenters the body, they contribute to active immunity.
G. Activating Cytotoxic and Helper T Cells
1. Like B cells, T cells have receptors.
2. Receptors of cytotoxic T cells and helper T cells cannot recognize an antigen simply present in lymph or blood.
3. Instead, an antigen must be presented to them by an antigen-presenting cell (APC).
a. When an antigen-presenting cell, usually a macrophage, engulfs a microbe, it is enclosed within an endocytic vesicle where it is broken down to release peptide fragments.
b. These fragments are antigenic, each of which is linked to an MHC protein; together they are displayed at the plasma membrane and are presented to a T cell. (Fig. 42.9) [transp. 233]
4. The importance of major histocompatibility complex (MHC) proteins was recognized when it was discovered they contribute to the difficulty of transplanting tissues from one person to another.
5. When donor and recipient are histocompatible, it is more likely a transplant will be successful.
6. When an APC presents an antigen to a helper T cell or cytotoxic T cell, the T cell recognizes the antigen.
a. If helper T cell recognizes antigen, it undergoes clonal expansion producing memory T cells that recognize antigen.
b. Once the cytotoxic T cell recognizes the antigen, it attacks and destroys any cell that possesses the antigen.
c. In this way T cells contribute to active immunity.
42.4. Immunity Can Be Induced (p. 767)
A. Two Types of Immunity
1. Immunity is acquired naturally through infection or can be brought about artificially by medical intervention.
a. Active immunity is where persons make their own antibodies.
b. Passive immunity is where an individual receives prepared antibodies.
B. Active Immunity Is Long-Lived
1. Active immunity sometimes develops naturally after a person is infected.
2. However, active immunity is often induced when a person is well so that future infection is prevented.
3. Immunization uses vaccines to induce active immunity; provides antigen to which immune system responds. (Fig. 42.10)
4. Edward Jenner used vaccine for smallpox; Louis Pasteur produced vaccines for cholera, anthrax and rabies.
5. To prepare these vaccines, the microbes were treated so they were no longer virulent.
6. Genetically engineered bacteria can produce proteins from microbes; the protein can be used as a vaccine.
7. After a vaccine is given, immune response is measured by amount of antibody in serum---the antibody titer.
a. After the first exposure, a primary response occurs with no antibodies and then a slow rise in the titer.
b. This is followed by a gradual decline as the antibodies bind to antigen or simply break down.
(Fig. 42.10b)
c. After a second exposure, a secondary response occurs in which the antibody titer rises rapidly to a plateau level much greater than with the primary immune response; this is a "booster."
d. High antibody titer of the secondary immune response is expected to prevent disease symptoms if individual is infected.
e. Immunological memory causes an individual to be actively immune.
C. Memory Cells Provide a State of Readiness
1. Immunological memory is dependent upon the number of memory B and T cells capable of responding.
2. Receptors of memory B cells usually have a higher affinity for antigen due to the selection process that occurred during first exposure; therefore they are prone to make IgG earlier.
3. Memory B and T cells respond to lower doses of antigen; immunity lasts as long as these cells are in blood.
4. Active immunity is usually long-lived.
D. Passive Immunity Is Short-Lived
1. Passive immunity occurs when an individual is given prepared antibodies to combat a disease.
2. Passive immunity is short-lived because the antibodies are not made by the individual's B cells.
3. Newborn infants are passively immune to disease because antibodies have crossed the placenta; breast-feeding promotes passive immunity- antibodies are in mother's milk.
4. Passive immunity is needed when an individual is in immediate danger from an infectious disease or a toxin.
5. For instance, a person exposed to a virus or toxin may be given a gamma globulin injection (serum that contains antibodies against the agent) perhaps taken from an individual who has recovered from it.
6. If antibodies are made with immunized horses, a few individuals become sick with serum sickness.
E. Cytokines Boost White Blood Cells
1. Cytokines are messenger molecules produced by either lymphocytes or monocytes.
2. They are lymphokines when produced by lymphocytes and monokines when produced by monocytes.
3. Because cytokines stimulate white blood cell formation, they may work as therapy for cancer and AIDS.
4. Both interferon and interleukins are used to improve ability of an individual's T cells to fight cancer.
5. Interferon produced by T cells is called a lymphokine; it has only been partly effective as an anticancer drug.
6. Cancer cells with altered proteins on their cell surface should be attacked by cytotoxic T cells.
7. Lymphokines may awaken the immune system and lead to the destruction of cancer.
a. Researchers first withdraw T cells from a patient and culture them in the presence of an interleukin.
b. Cells are reinjected into patient who is given doses of interleukin to maintain killer activity of the T cells.
8. Interleukin antagonists may be helpful to prevent skin or organ rejection, autoimmune diseases, and allergies.
F. Monoclonal Antibodies Have Same Specificity
1. Every plasma cell derived from the same B cell secretes antibodies against a specific antigen; these are monoclonal antibodies.
2. Monoclonal antibodies can be produced in vitro. (Fig. 42.12)
a. B lymphocytes are removed from the body (usually mice are used) and exposed to a particular antigen.
b. Activated B lymphocytes are fused with myeloma cells that are malignant plasma cells that divide indefinitely.
c. The fused cells are called hybridomas because they result from two different cells and one is cancerous.
3. Monoclonal antibodies are used for quick and reliable diagnosis of various conditions such as pregnancy.
4. They can also identify infections, sort out different T cells, and distinguish between normal and cancer cells.
42.5. Immunity Has Side Effects (p. 769)
A. Allergies: Overactive Immune System
1. An allergy results from an overactive immune system forming antibodies to everyday substances.
2. Allergies produce coldlike symptoms; a severe systemic reaction is anaphylactic shock, a sudden drop in blood pressure.
3. Of the five antibodies, IgE antibodies are involved in allergic reactions.
a. IgE antibodies are found in bloodstream; unlike other antibodies, they also reside on mast cells in tissues.
b. Mast cells are basophils that have left the bloodstream and reside in tissues.
c. When an allergen attaches to IgE antibodies bound to mast cells, these cells release large amounts of histamine and other substances, which cause mucus production and airway constriction.
d. Increased capillary permeability can lead to fluid loss and shock.
4. Allergy shots sometimes prevent the onset of allergic symptoms.
a. Injections of the allergen cause the body to build up high quantities of IgG antibodies.
b. These combine with allergens received from the environment before they have a chance to reach IgE antibodies located on the plasma membrane of mast cells.
B. Autoimmune Diseases: The Body Attacks Itself
1. Autoimmune diseases result as an attack on tissues by the body's own antibodies and T cells.
2. The cause is not known but autoimmune diseases often appear following recovery from an infection.
3. Some bacteria produce toxic products that cause T cells to bind prematurely to macrophages; the T cell might learn to recognize the body's own tissues.
4. In multiple sclerosis (MS), the myelin sheath of nerve fibers is attacked.
5. In myasthenia gravis, neuromuscular junctions do not work properly and muscular weakness results.
6. A person with systemic lupus erythematosus presents many symptoms before dying from kidney damage.
7. Heart damage following rheumatic fever and type I diabetes are also autoimmune diseases.
8. There are no cures for autoimmune diseases.
C. Tissue Rejection: Foreign MHC Proteins
1. Tissue rejection occurs because cytotoxic T cells cause disintegration of foreign tissue.
2. Selection of compatible organs and administration of immunosuppressive drugs prevent tissue rejection.
3. Cyclosporine and tacrolimus (FK-506) help in immunosuppression in liver transplants but may hurt kidneys.