Lecture Outline - Chapter 14

14.1. Lymphatic System (p. 250)

1. Lymph system is closely associated with cardiovascular system.
2. Functions
   • a. Takes up excess tissue fluid and returns it to bloodstream.
   • b. Absorbs fats in intestinal villi and transports them to bloodstream.
   • c. Helps defend body against disease.
3. Lymphatic Vessels Transport One Way
   • a. Most body regions richly supplied with lymphatic capillaries. (Fig. 14.1)
   • b. Structure of larger lymph vessels similar to veins including presence of valves.
   • c. Movement of lymph depends upon skeletal muscle contraction, similar to veins.
   • d. Lymph capillaries take up unabsorbed tissue fluid.
   • e. Edema is local accumulation of fluid in tissue causing swelling.
   • f. Once within lymph vessels, fluid is termed lymph.
   • g. Lymphatic capillaries join to form two ducts:
     • i. Right lymphatic duct serves right arm, right side of head and neck, and right thoracic area.
     • ii. Larger thoracic duct serves left arm and thoracic area, abdomen and lower body.
   • h. Both ducts drain into the subclavian veins in the thorax.
4. Lymphoid Organs Assist Immunity (Fig. 14.2) (p. 251)
5. a. Lymph Nodes
   • i. Small (1- 25 mm) round structures.
   • ii. Found at points along lymphatic vessels.
   • iii. Have fibrous connective tissue capsule with incoming and outgoing lymphatic vessels.
   • iv. Each nodule contains sinus filled with lymphocytes and macrophages.
   • v. Occur singly or in groups of nodules:
     - Tonsils are located in back of mouth on either side.
     - Adenoids on posterior wall above border of soft palate.
     - Peyer's patches found within intestinal wall.

     vi. Lymph nodes occur in regions: axillary nodes in armpits and inguinal nodes in groin.
6. b. Spleen
   • i. Located in upper left abdominal cavity just beneath diaphragm.
   • ii. Structure similar to lymph node; outer connective tissue divides organ into lobules with sinuses.
   • iii. Lobules contain sinuses filled with blood.
   • iv. Blood vessels of spleen can expand; therefore spleen functions as blood reservoir; makes blood available in times of low pressure or oxygen need.
   • v. Spleen has red pulp containing RBCs, lymphocytes, and macrophages; functions to remove bacteria and worn-out red blood cells.
   • vi. White pulp contains mostly lymphocytes. Both help to purify the blood.
7. c. Thymus
   • i. Located along trachea behind sternum in upper thorax.
   • ii. Larger in children; disappears in old age.
   • iii. Divided into lobules where T lymphocytes mature.
   • iv. Interior (medulla) of lobule secretes thymosin thought to aid T cells to mature.
8. d. Red Bone Marrow
   • i. Site of origin of all types of blood cells.
   • ii. Five types of white blood cells (WBCs) function in immunity. (Fig. 14.3)
   • iii. Stem cells continuously divide to produce cells that differentiate into various blood cells.
   • iv. Most bones of children have red blood marrow.
   • v. In adult, red marrow is found in the skull, sternum, ribs, clavicle, spinal column, femur, and humerus.
   • vi. Red blood marrow has network of connective tissue where reticular cells produce reticular fibers; these plus stem cells fill sinuses; differentiated blood cells enter bloodstream at these sinuses.

1. Immunity is ability to defend against infectious agents, foreign cells, and abnormal body cells including cancer.
2. Nonspecific defenses include barriers to entry, inflammatory reaction, and protective proteins.
3. Barring Entry
   • a. Skin and mucous membranes line respiratory, digestive and urinary tracts; form mechanical barrier to entry by microbes.
   • b. Oil gland secretions contain chemical that weakens bacteria on skin.
   • c. Cilia and mucus in respiratory tract sweep up or trap particles.
   • d. Stomach acids inhibit bacterial growth in stomach.
   • e. A mix of natural harmless bacteria in intestine and vagina prevent pathogens from growing.
4. Phagocytizing the Enemy
   • a. Inflammatory reaction begins when skin is broken.
   • b. Inflammation symptoms are redness, pain, swelling, and heat. (Fig. 14.4)
   • c. Mast cells are derived from basophils.
   • d. Injured tissues rupture and release bradykinin which:
     • i. initiates nerve impulses resulting in pain.
     • ii. stimulates mast cells to release histamine, which in turn causes capillaries to dilate, causing reddening.
     • iii. allows proteins and fluid to escape, resulting in swelling.
     • iv. increases body temperature reducing invading bacteria.
   • e. Neutrophils and monocytes are amoeba-like and phagocytize (eat) bacteria.
   • f. Monocytes differentiate into macrophages that can eat hundreds of bacteria or viruses and trigger an increase in white blood cell numbers.
   • g. Pus forms as a thick, whitish fluid containing dead neutrophils, bacteria, and living WBCs.
5. Chemo Warfare
   • a. The Complement System
     • i. A group of proteins designated by letter C and a subscript.
     • ii. Complement proteins activate other proteins in domino fashion.
     • iii. Orderly cascade of reactions may result in:
       - attracting phagocytes to scene of invasion.
       - bind to surface of microbes to ensure white blood cells will phagocytize the microbe.
       - produce holes in bacterial cell walls and membranes. (Fig. 14.5)
   • b. Interferon
     • i. Protein produced by virus-infected cells.
     • ii. Binds to receptors of noninfected cells, causing cells to produce substance that interfere with viral replication.
     • iii. Interferon is specific to species; humans need human interferon.
     • iv. Interferon is made in quantity by recombinant DNA technology.

1. Immunity formed against a specific foreign agent, bacteria, or protein.
2. Immune system is able to distinguish self from nonself.
3. Antigens are proteins or carbohydrate chain of a glycoprotein within a plasma membrane that the body recognizes as nonself.
4. Immunity usually lasts for some time; for instance, usually cannot get measles a second time.
5. Immunity is primarily result of two types of lymphocytes:
   • a. B Lymphocytes
     • i. Derived from and mature in the bone marrow.
     • ii. Become plasma cells that produce and secrete antibodies into blood.
   • b. T Lymphocytes
     • i. Derived from the bone marrow.
     • ii. Mature in the thymus gland.
     • iii. Either directly attack antigen-bearing cells or help regulate the immune response.
   • c. Recognition of antigen by lymphocyte is due to complementary shape of the receptor to the specific antigen, like a lock and key.
   • d. Estimated one million different antigens encountered in lifetime; require one million different lymphocytes.
6. B Cells: Make Plasma and Memory Cells (p. 255)
   • a. Each type of B cell carries specific antibody as membrane-bound receptor on surface; receptor is antibody that binds to antigen on a bacterial cell.
   • b. B cells in lymph node of spleen exposed to bacteria or toxin are activated to divide many times, forming clone of identical plasma cells.
   • c. Clonal selection theory states antigen selects which B cells produce clone of plasma cells. (Fig. 14.6)
   • d. Some of clone cells do not participate in antibody production; remain in blood as memory B cells; if same antigen invades the system again, they divide and produce new plasma cells secreting same antibody into blood.
   • e. Termed antibody-mediated immunity because B cells produce antibodies.
   • f. Also called humoral immunity because antibodies are released into bloodstream.
7. How Antibodies Work (p. 256)
   • a. Most common type of antibody is protein molecule shaped like a letter Y.
   • b. Each arm of Y has a long "heavy" polypeptide chain and a short "light" chain of amino acids.
   • c. Upper arm chains have constant regions where sequence of amino acids is set, and variable regions, where sequence varies. (Fig. 14.7)
   • d. Constant lower region is the same within each class of antibodies. (Table 14.1)
   • e. Variable region forms antigen-binding site specific to particular antigen; combines with antigen in lock- and-key manner.
   • f. Antigen-antibody complexes usually marked for destruction by phagocytosis.
8. How Antibodies Differ (p. 256)
   • a. Five different classes of circulating antibodies. (Table 14.1)
   • b. IgG antibodies are major type in blood, lesser amounts in lymph and tissue fluid; attacks microbes and toxins.
   • c. IgM antibodies are pentamers containing five Y-shaped structures; appear soon after infection begins and soon disappear; activators of complement system. (Fig. 14.7a)
   • d. IgA antibodies are dimers; contain two Y-shaped structures; are main antibody found in body secretions; attack microbes and toxins before reach bloodstream.
   • e. Limited number of IgD antibodies of uncertain function.
   • f. IgE antibodies are responsible for allergic reaction.
9. T Cells Become Cytotoxic, Helper, Memory, or Suppressor Cells (p. 258)
   • a. Types of T cells look alike but are distinguished by function.
     • i. Cytotoxic T Cells
       - Sometimes called killer T cells.
       - Attack and destroy viral infected or cancerous cells.
       - Responsible for cell-mediated immunity.
       - Storage granules inside cytotoxic T cells contain perforin, a chemical that perforates plasma membranes so that water/salts can enter and rupture the cell. (Fig. 14.8)

       ii. Helper T Cells

       - Help regulate immunity by increasing response of other immune cells.

       - They secrete lymphokines when exposed to antigen that cause more helper T cells to clone, macrophages to phagocytize, and B cells to make antibodies.

       - Because the AIDS virus (HIV) attacks helper T cells, it inactivates immune system.

       iii. Suppressor T Cells

       - Regulates immune response by suppressing development of helper T cells.

       - Since T cells stimulate B cell production, suppressor cells control overproduction of both.

       - Memory T cells persist, sometimes for life, and protect in case of reinfection.
   • b. Activating Cytotoxic and Helper T Cells (p. 259)
     • i. Cytotoxic T cells and helper T cells are unable to recognize antigens in lymph or blood.
     • ii. Requires an antigen-presenting cell (APC), usually macrophages.
     • iii. Macrophage engulfs microbe, encloses it within endocytic vesicle, and enzymatically breaks it down to release peptide fragments.
     • iv. Fragments are antigenic.
     • v. Fragments are linked to MHC (major histocompatible complex) protein and are presented together on plasma membrane to T cell.
     • vi. MHC proteins first detected in difficulty of transplanting tissue from donor to recipient; the closer the donor-recipient proteins, the more successful the transplant.
     • vii. Macrophage presents antigen to helper T cell; helper T cell undergoes clonal expansion, producing memory T cells; cytotoxic T cells attack and destroy infecting agent; T cells contribute to active immunity.

1. Immunity can be acquired naturally through infection or artificially by medical intervention.
2. Medically induced immunity is of two types: active (where an individual produces own antibodies against antigen) and passive (where individual receives prepared antibodies).
3. Active Immunity Is Long-Lived
   • a. Develops naturally after person is infected with microbe.
   • b. Artificial immunization against foreign agent when person is healthy prevents future infection.
   • c. Immunization uses vaccines, substances that contain antigens to which immune system can respond.
     • i. Vaccine can be made from microbial agent itself; requires altering agent so it can no longer cause full disease (no longer virulent).
     • ii. Genetically engineered bacteria can produce just the surface protein of a microbe.
     • iii. Several vaccines can be produced for a combination vaccination, utilizing surface proteins from several disease agents.
   • d. Provides longer lasting protection.
   • e. Primary response is gradual.
     • i. It takes several days before antibodies appear.
     • ii. Antibody titer is amount of antibody present in serum.
     • iii. Titer slowly rises, evens off, then falls as antibodies bind to antigen or break down. (Fig. 4.10)
   • f. Secondary response is rapid.
     • i. A second injection causes a quick rise in titer; titer level is much higher than primary response.
     • ii. More plasma and memory cells are present to produce antibodies rapidly.
     • iii. Called a "booster shot" because it boosts antibody titer to high level.
4. Memory Cells Provide a State of Readiness
   • a. Immunological memory depends on number of memory B and memory T cells responding to particular antigen.
   • b. Receptors on memory B cells have higher affinity for antigen due to selection process during first exposure; prone to make IgG earlier.
   • c. Active immunity lasts as long as clones of memory B and memory T cells are present.
5. Passive Immunity is Short-lived.
   a. Passive immunity occurs when individuals receive prepared antibodies (immunoglobulins) to combat the disease.
   • b. Since the individual does not produce these antibodies, immunity is short-lived.
   • c. Antibodies that cross placental membranes to fetus are example; disappear in several months.
   • d. Breast-feeding prolongs natural passive immunity; antibodies are passed along in mother's milk when infant nurses. (Fig. 14.11)
   • e. Injections of gamma globulin serum that contains antibodies can prevent full illness from developing in patient just exposed to serious agents with no time to develop active immunity from immunization.
   • f. Serum has traditionally been harvested from plasma of immunized horses to produce antitoxins for diphtheria, botulism, and tetanus.
   • g. Serum sickness occurs when patient reacts to foreign proteins in horse serum, etc.
6. Cytokines Boost White Blood Cells (p. 262)
   • a. Cytokines are messenger molecules produced by lymphocytes (producing lymphokines) or monocytes (producing monokines) .
   • b. Stimulate immune system; are of possible use in fighting cancer and AIDS.
   • c. Interferon is produced by leukocytes and fibroblasts in response to viral infection; if produced by T cells, it is called a lymphokine.
   • d. Interleukin may be used as adjuncts for vaccines; researchers withdraw patient's T cells, activate them by culturing in presence of an interleukin, reinject into patient and use doses of interleukin to maintain killer activity of T cells.
7. Monoclonal Antibodies Have Same Specificity
   • a. Monoclonal antibodies are antibodies of the same type because they are produced by plasma cells derived from the same B cell.
   • b. Monoclonal antibodies can be produced outside the body in glassware (in vitro) (Fig. 14.12)
   • c. Uses:
     • i. Diagnosis of pregnancy.
     • ii. Diagnosis of infections.
     • iii. Carry radioactive isotopes or toxic drugs to tumor cells.
   • d. Monoclonal antibodies are a biotechnology product since their production requires a living system.

1. Immune system can be underprotective when fails to recognize abnormal cancerous growth or overprotective when we cannot receive other types of human blood.
2. Finding Compatible Blood--The ABO System
   • a. The surface membranes of RBCs carry proteins that act as antigens in some recipients.
   • b. ABO blood system results from antigens A and B. (Table 14.2)
     - O type blood lacks both A and B antigens.
     - A type blood has A antigens only.
     - B type blood has B antigens only.
     - AB type blood has both A and B antigens present.

     c. Blood plasma contains antibodies to the blood types not present.

     d. Exposure to foreign blood antigens results in agglutination or clumping of RBCs, prevents circulation of blood, and the RBCs burst.

     e. Blood typing relies on antigen-antibody agglutination.
3. Rh System: Pregnancy Risks (p. 264)
   • a. Also an important antigen used in matching blood types.
   • b. Persons with Rh factor on RBC membrane are Rh positive; Rh negative lack the Rh factor protein.
   • c. Rh negative individuals do not automatically have antibodies to Rh factor but develop immunity when exposed to it.
   • d. Hemolytic disease of the newborn (HDN) can occur when mother is Rh negative and baby is Rh positive.
     - Mother is not exposed to infants blood unless baby's RBCs leak across placenta; otherwise mother is only "inoculated" with small amount of baby's blood (and Rh protein) at birth.
     - Mother builds up antibodies that are small enough to pass placenta and can destroy baby's RBC; mother receives a booster at each baby's birth; therefore danger to successive infants grows.
     - Problem is solved by giving the mother anti-Rh antibodies, usually after baby's birth, that attack any of baby's RBCs left in mother's blood before mother can produce antibodies.
4. Allergies: Overactive Immune System (p. 265)
   • a. Allergies are caused by an overactive immune system.
   • b. Antibodies are produced to substances that are not usually recognized as being foreign.
   • c. Allergy symptoms vary from cold-like symptoms to dangerous anaphylactic shock, a sudden drop in blood pressure.
   • d. The antibody IgE is found both in bloodstream and resides in membrane of mast cells found in tissues.
   • e. When allergen (antigen that provokes an allergic reaction) attaches to the IgE antibodies on mast cells, histamine is released.
   • f. Histamine increases capillary permeability which releases mucus and constricts the airways.
   • g. Allergy shots build up IgG antibodies that combine with the allergen before they reach IgE.
5. Tissue Rejection: Foreign MHC Proteins
   • a. Organs such as skin, heart, kidneys, etc., could be transplanted easily from person-to-person except for tissue rejection.
   • b. Cytotoxic T cells cause disintegration of foreign tissue.
   • c. Can be avoided through careful selection of organ to be transplanted; closely matched transplanted organs are often from relatives with same type of MHC proteins as recipient.
   • d. Otherwise immunosuppressive drugs (Cyclosporine and FK-506) must be used to inhibit production of interleukin-2; both adversely affect kidneys.
6. Autoimmune Diseases: The Body Attacks Itself
   • a. Autoimmune diseases are caused when cytotoxic T cells and normal antibodies attack an individual's own body cells.
   • b. Exact cause of autoimmune disease is unknown; often occurs after recovery from infection.
   • c. Some bacteria produce toxic products that cause T cells to bind to macrophages; perhaps this is how T cells learn to recognize the body's own tissues, which they now attack.
   • d. Autoimmune diseases include:
     - myasthenia gravis where neuromuscular junctions do not work properly and muscular weakness results.
     - multiple sclerosis where myelin sheath of nerve fibers is attacked.
     - rheumatoid arthritis affecting the joints.
     - systemic lupus erythematosus with many symptoms but ending with kidney damage.
     - heart damage following rheumatic fever and Type I diabetes.