1. Chapter 14: Lymphatic and Immune Systems

2. The Lymphatic System The lymphatic system has three main functions:
lymphatic vessels return excess tissue fluid to the bloodstream,
lacteals in the small intestine receive and transport lipoproteins, and
lymphoid organs work with the immune system to combat disease.

3. Lymphatic Vessels
The lymphatic vessels are similar in structure and function to veins; movement of lymph is dependent upon skeletal muscle contraction, and internal valves prevent backflow.
Lacteals collect fat molecules at intestinal villi and lymphatic capillaries collect excess tissue fluid at blood capillaries.

4. Tissue fluid becomes lymph once it enters the lymphatic capillaries.
Lymphatic capillaries merge to form larger lymphatic vessels that carry lymph to the subclavian veins.
Edema is retention of fluids in the tissues due to a blockage of the flow of lymph.

5. Lymphatic system
Lymphatic vessels drain excess fluid from the tissues and return it to the cardiovascular system. The enlargement shows that lymphatic vessels, like cardiovascular veins, have valves to prevent backward flow. The lymph nodes, tonsils, spleen, thymus gland, and red bone marrow are the lymphoid organs that assist immunity.

6. Lymphoid Organs
Lymphoid organs include the lymph nodes, tonsils, spleen, thymus gland, and the red bone marrow.
Lymph nodes are located at certain points along lymphatic vessels and contain a cortex and a medulla.
The cortex contains nodules where lymphocytes congregate when fighting off a pathogen.

7. Macrophages are concentrated in the medulla where they work to cleanse the lymph.
Tonsils are patches of lymphatic tissue in the pharynx; they are the first to encounter pathogens in the nose and mouth.
Tonsils perform functions similar to those of the lymph nodes.
The spleen cleanses blood of pathogens and their toxins.

8. B lymphocytes mature in the red bone marrow.
The thymus is located behind the sternum and is the site in which T lymphocytes mature.
The thymus produces the hormone thymosin that appears to cause T lymphocytes to mature; thymosin may play other roles in immunity.
The red bone marrow is the site where all types of blood cells are produced by stem cells.
B lymphocytes mature in the red bone marrow.
The red bone marrow consists of a network of connective tissue fibers, called reticular fibers, which are produced by cells called reticular cells. These and the stem cells and their progeny are packed around thin-walled sinuses filled with venous blood. Differentiated blood cells enter the bloodstream at these sinuses. In a child, most bones have red bone marrow, but in an adult it is present only in the bones of the skull, the sternum (breastbone), the ribs, the clavicle, the pelvic bones, and the vertebral column.

9. The lymphoid organs
The lymphoid organs include the lymph nodes, the tonsils (not shown in an enlargement), the spleen, the thymus gland, and the red bone marrow, all of which contain lymphocytes.

10. Nonspecific Defenses
The immune system includes cells and tissues that are responsible for immunity.
Immunity is the body’s ability to defend against infection and involves nonspecific and specific defenses.
The nonspecific defenses are effective against many types of infectious agents.

11. Barriers to Entry
Skin and mucous membranes lining the respiratory, digestive and urinary tracts, oil glands in the skin, ciliated cells that sweep particles in mucus, and an acidic stomach all contribute to keeping pathogens from entering the body.
Beneficial bacteria in the intestines and vagina also prevent pathogens from taking up residence.

12. Inflammatory Reaction
The inflammatory reaction involves redness, heat, swelling, and pain.
The release of histamine and kinins from damaged tissue cells and from mast cells causes redness and swelling.
The swollen area and kinins stimulate free nerve endings, causing the sensation of pain.

13. Macrophages migrate to the site of injury and can engulf pathogens and also release colony-stimulating factors that cause the bone marrow to release more white blood cells.
Anti-inflammatory drugs combat chronic inflammation by acting against chemical mediators released by white blood cells.
The presence of pus indicates the body is trying to overcome the infection.

14. Inflammatory reaction
Injured tissue cells and mast cells release inflammatory chemicals (e.g., histamine) that dilate capillaries, bringing blood to the scene. Redness and heat result. Permeability of the capillary causes a local inflammation of tissue fluid. Swelling stimulates free nerve endings, resulting in pain. Blood clots wall off the capillary, preventing blood loss. Neutrophils and monocytes squeeze through the capillary wall and begin to phagocytize pathogens. Monocytes become aggressive macrophages, which quickly phagocytize pathogens and stimulate the immune response.

15. Natural Killer Cells
Natural killer cells kill virus-infected cells and tumor cells by cell-to-cell contact.
They are large, granular lymphocytes with no specificity and no memory.
Their number is not increased by prior exposure to that kind of cell.

16. Protective Proteins
The complement system, or complement, refers to a number of plasma proteins that assist nonspecific immunity.
A small amount of activated complement protein is needed to activate a cascade of other proteins.
Complement is activated when pathogens enter the body.

17. Complement amplifies the inflammatory reaction by attracting phagocytes and promoting phagocytosis.
Some complement proteins join to form pores in the surface of bacteria and cause them to burst.
Interferon is a protein produced by virus-infected cells that prepares non-infected cells for attack and interferes with viral replication; it is specific to species.

18. Action of the complement system against a bacterium
When complement proteins in the plasma are activated by an immune response, they form holes in bacterial cell walls and plasma membranes, allowing fluids and salts to enter until the cell eventually bursts. On the left, complement proteins form holes in the bacterial cell wall and membrane. In the center, holes allow fluids and salts to enter the bacterium. On the right, the bacterium expands until it bursts.

19. Specific Defenses
An antigen is any foreign substance that stimulates the immune system to react to it.
The body does not consider its own proteins foreign; therefore the immune system must distinguish self from nonself.
Lymphocytes have a large number of antigen receptors.
Diversification occurs to such an extent during the maturation process that there is a lymphocyte type for any possible antigen.

20. Specific defenses require B lymphocytes (B cells) and T lymphocytes (T cells), which are both produced in the bone marrow; however, T cells mature in the thymus, while B cells mature in bone marrow.
B cells give rise to antibodies that are shaped like antigen receptors and are capable of combining with and neutralizing antigens.
T cells do not produce antibodies but instead attack foreign antigens directly.

21. B Cells and Antibody-Mediated Immunity
A toxin is a chemical produced by certain bacteria that is poisonous.
As a B cell encounters a bacterial cell or a toxin with a specific antigen in a lymph node or spleen, it is activated to divide.
The resulting cells are plasma cells, mature B cells that mass-produce antibodies.
Defense by B cells is thus called antibody-mediated immunity.
B cells are stimulated to divide and become plasma cells by helper T cell secretions called cytokines.

22. According to the clonal selection theory, it is the antigen that selects which lymphocyte will undergo clonal expansion, mass producing lymphocytes bearing matching antigen receptors.
Some members of the clone become memory B cells that remain in the body to divide and produce more lymphocytes able to secrete antibodies if the same antigen is encountered at a later date.
When infection passes, plasma cells undergo apoptosis.

23. Clonal selection theory and B cells
When an antigen combines with a B cell’s antigen receptors and is stimulated by T cell secretions called cytokines, the B cell undergoes clonal expansion. The result is many plasma cells, which produce specific antibodies against this antigen along with memory B cells. After the infection passes, plasma cells undergo apoptosis. Memory B cells, which keep the ability to recognize this antigen, are retained in the body.

24. Structure of IgG
The most common type of antibody, the IgG antibody, is a Y-shaped molecule that has two binding sites for a specific antigen.
Antigen-antibody complexes often mark the antigen for destruction by neutrophils or macrophages, or they may activate complement.

25. Structure of IgG
In the diagram at the top, an IgG antibody contains two heavy (long) polypeptide chains and two light (short) chains arranged so there are two variable regions, where a particular antigen is capable of binding with an antibody (V=variable region, C = constant region). In the lower diagram is a computer generated model of an antibody molecule. The antigen combines with the two side branches.

26. Other Types of Antibodies
There are five types of antibodies:
IgG – the main type in circulation, binds to pathogens, activates complement, and enhances phagocytosis
IgM – the largest type in circulation, activates complement and clumps cells
IgA – found in saliva and milk, prevents pathogens from attaching to epithelial cells in digestive and respiratory tracts

27. IgD – on surface of immature B cells, its presence signifies the readiness of a B cell
IgE – found as antigen receptor on basophils in blood and on mast cells in tissues, responsible for immediate allergic response and protection against certain parasitic worms.
The different classes of antibodies vary in structure.

28. T Cells and Cell-Mediated Immunity
T cells mature in the thymus.
Like B cells, each T cell bears a specific receptor, however, for a T cell to recognize an antigen, the antigen must be presented by an antigen-presenting cell (APC).
When a viral or cancer cell antigen is presented, the antigen is first linked to a major histocompatibility complex (MHC) protein.
T cells are active against viruses and body cells that have become cancerous.

29. Human MHC proteins are called HLA (human lymphocyte-associated) antigens; HLA antigens are self proteins that identify tissues as belonging to the body (the basis of tissue transplant rejection).
Once a T cell’s antigen receptor matches up to its specific antigen presented to it by a macrophage (the APC), the T cell becomes activated and secretes cytokines and undergoes clonal expansion.
Cytokines are signaling chemicals that stimulate various immune cells and many copies of activated T cells are produced.

30. Clonal selection theory and T cells
Each type of T cell bears a specific antigen (note different colors). Activation of a T cell occurs when its antigen receptor can combine with an antigen. A macrophage presents the antigen (note red circle) in the groove of an HLA molecule. Thereafter, the T cell undergoes clonal expansion, meaning that many copies of the same type of T cell are produced. (Note that all T cells on the right have blue antigen receptors.) After the immune response has been successful, the majority of the T cells undergo apoptosis, while a small number become memory T cells. Memory T cells provide protection should the same antigen enter the body again at a future time.

31. Types of T Cells
Cytotoxic T cells kill infected cells that bear a foreign antigen on contact using perforin molecules; cytotoxic T cells provide cell-mediated immunity.
Helper T cells stimulate other immune cells and produce cytokines.
Some T cells are memory T cells that will jump-start an immune reaction upon re-infection.
Cytotoxic T cells have storage vacuoles containing perforin molecules. Perforin molecules perforate a plasma membrane, forming a pore that allows water and salts to enter a cell. The cell then swells and eventually bursts.

32. Cell-mediated immunity
On the left, the scanning electron micrograph shows cytotoxic T cells attacking and destroying a cancer cell. Cancer cells are subject to attack because they have acquired nonself antigens. On the right, during the killing process, the vacuoles in a cytotoxic T cell release perforin molecules. These molecules combine to form pores in the target cell plasma membrane. Thereafter, fluid and salts enter so the target cell eventually bursts.

33. Induced Immunity
Immunity occurs naturally by infection or is induced by medical intervention.
The two types of induced immunity are active immunity and passive immunity.
In active immunity, the individual produces the antibodies against an antigen.
In passive immunity, the individual is given prepared antibodies.

34. Active Immunity
A person naturally develops active immunity after infection.
Immunization involves the use of vaccines, substances that contain an antigen to which the immune system responds.
Vaccines are available to induce long-lived active immunity in a well person.
Figure 14.9 (page 272) lists the suggested immunization schedule for children in the United States.

35. After exposure to a vaccine, which is a non-virulent disease agent, antibodies are produced.
With a booster shot or second exposure, the antibody titer rises to a much higher level.
Active immunity is long-lived because there are memory B cells and memory T cells that will respond to lower doses of antigen in the body.
A pathogen that is virulent is one that is able to cause disease.

36. Active immunity due to immunizations
During immunization, the primary response, after the first exposure to a vaccine, is minimal, but the secondary response, which may occur after a second exposure, shows a dramatic rise in the amount of antibody present in plasma.

37. Passive Immunity
Passive immunity occurs when an individual is given prepared antibodies.
For example, a newborn has antibodies that passed from its mother through the placenta.
Breast-feeding passes antibodies from mother to child.
However, passive immunity is short-lived since the antibodies were not produced by the person’s own B cells.

38. Passive immunity
Breast-feeding is believed to prolong the passive immunity an infant receives from the mother because antibodies are present in the mother’s milk.

39. Cytokines and Immunity
Cytokines are signaling molecules produced by T lymphocytes, monocytes, and other cells.
Both interferon and interleukins are cytokines used to improve a person’s own T cell performance in fighting cancer.
Interleukins show promise in the treatment of chronic infectious diseases.
Interleukin antagonists also may prove helpful in preventing skin and organ rejection, autoimmune diseases, and allergies.

40. Monoclonal Antibodies
All plasma cells derived from the same B cell secrete an identical antibody.
B lymphocytes can therefore be exposed to a particular antigen and will produce monoclonal antibodies to the specific antigen.
Activated B lymphocytes are fused with myeloma cells and these hybridomas produce only one type of antibody.
Monoclonal antibodies are most often used in diagnostic procedures such as pregnancy tests but could carry isotopes to destroy cancerous tumors.

41. Production of monoclonal antibodies
Plasma cells (derived from immunized mice) are fused with myeloma (cancerous) cells, producing hybridoma cells that are “immortal”. Hybridoma cells divide and continue to produce the same type of antibody, called monoclonal antibodies.

42. Immunity Side Effects
The immune system usually protects us from disease because it can distinguish self from nonself.
Sometimes, however, it responds in a manner that harms the body.
Examples include allergies, tissue-rejection reactions, or autoimmune diseases.

43. Allergies
Allergies are hypersensitivities to substances such as pollen or animal dander that are normally not harmful.
Weak antigens such as these are called allergens.
The response itself can cause some degree of tissue damage.

44. Immediate Allergic Response
An immediate allergic response can occur within seconds after contacting an antigen.
Anaphylactic shock is a severe reaction characterized by a sudden life-threatening drop in blood pressure.
Immediate allergic responses are caused by IgE antibodies attaching to mast cells and basophils; these cells then release histamine which causes the symptoms of allergies, some of which are severe.
Allergy shots sometimes prevent the onset of an allergic response by building up quantities of IgG antibodies. IgG antibodies then combine with the allergens before they reach the IgE antibodies located in the mast cells or basophils.

45. Delayed Allergic Response
Delayed allergic responses are started by memory T cells at the site of the allergen.
The response is regulated by cytokines secreted by T cells and macrophages.
Examples of delayed allergic responses include the skin test for tuberculosis and contact dermatitis from poison ivy, jewelry, and other possible irritants.
A classic example of a delayed allergic response is the skin test for tuberculosis. When the result of the test is positive, the tissue where the antigen was injected becomes red and hard. This shows that there was prior exposure to tubercle bacilli, the cause of tuberculosis.

46. Blood-Type Reactions
Illness and death sometimes resulted from the first attempts at blood transfusions.
It was later discovered that only certain types of blood are compatible because red blood cell membranes carry proteins or sugar residues that are antigenic to recipients.
The ABO blood system represents a series of antigens on red blood cells that denote blood type.

47. ABO System
The ABO blood typing system is based on the presence of two antigens on the surface of red blood cells; antigen A and antigen B.
Blood types include A, B, or AB, or type O, which has no antigens.
In the plasma there are two possible naturally-occurring antibodies: anti-A and anti-B.
A summary of the ABO blood types and their distribution among ethnic groups is shown in Table 14.2, page 276.

48. If the corresponding antigen and antibody are put together, clumping, or agglutination, occurs; in this way the blood type of the individual may be determined.

49. Blood typing
The standard test to determine ABO and Rh blood type consists of putting a drop each of anti-A antibodies, anti-B antibodies, and anti-Rh antibodies on a slide. To each of these, a drop of the person’s blood is added. If agglutination occurs, as seen in the photo at the top right, the person has this antigen on red blood cells. The chart shows several possible results.

50. Rh System
The Rh factor is also a blood type; a person with this antigen on their red blood cells is Rh positive (Rh+); those without it are Rh negative (Rh-).
Rh factor is important during pregnancy because an Rh- mother may form antibodies to the Rh antigen during the pregnancy or at the birth of a child who is Rh+.

51. These antibodies can cross the placenta to destroy the red blood cells of any subsequent Rh+ child, causing hemolytic disease of the newborn.
A Rho-Gam injection uses anti-Rh antibodies to attack Rh+ cells before they can stimulate the mother to produce her own antibodies.

52. Hemolytic disease of the newborn
Due to a pregnancy in which the child is Rh positive, an Rh negative mother can begin to produce antibodies against Rh+ red blood cells. In another pregnancy, these antibodies can cross the placenta and cause hemolysis of an Rh+ child’s red blood cells.

53. Tissue Rejection
Tissue rejection occurs when cytotoxic T cells bring about the destruction of foreign tissue in the body.
A close match between donor and recipient can reduce rejection.
Immunosuppressive drugs act by inhibiting the response of T cells to cytokines, but can result in kidney damage.
The hope is that tissue engineering, the production of organs that lack antigens or can be protected in some way from the immune system, will one day do away with the problem of rejection.

54. Autoimmune Diseases
Autoimmune disease occurs when cytotoxic T cells or antibodies mistakenly attack the body’s own cells as if they bear foreign antigens.
Autoimmune diseases include: myasthenia gravis, multiple sclerosis, systemic lupus erythematosus, and rheumatoid arthritis.
It has been suggested that type I diabetes and heart damage after rheumatic fever are autoimmune diseases.
As yet, there are no cures for autoimmune diseases, but they can be controlled with drugs.

55. Chapter Summary
Lymphatic vessels form a one-way system that transports lymph from tissues and fat from lacteals to specific cardiovascular veins.
Lymphoid organs include the red bone marrow, spleen, thymus, and lymph nodes that all play critical roles in defense mechanisms.

56. Immunity consists of nonspecific and specific defenses to protect against disease.
Nonspecific defenses consist of barriers to entry, the inflammatory reaction, natural killer cells, and protective proteins.
Specific defenses involve two types of lymphocytes: B lymphocytes and T lymphocytes.

57. Medically induced immunity involves use of vaccines to achieve long-lasting immunity and use of antibodies to provide temporary immunity.
While immunity protects us, it is also responsible for undesirable effects, such as allergies, autoimmune diseases, and tissue rejection.