10. Figure 22.3 C. Lymphatic Tissue and Organs: 1. Lymphatic organs contain lymphatic tissue which consists primarily of lymphocytes, but also include

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1 Chapter 22 Lymphatic Systems & Immunity I. Lymphatic System: a) includes lymph, lymphatic vessels, lymphatic tissue, lymphatic nodes, tonsils, the spleen, and the thymus. A. Functions of the Lymphatic System: 1. Fluid balance: a) 3 liters of fluid enters the lymphatic capillaries, where the fluid is called lymph and passes back to the blood. b) In addition to water, lymph contains solutes derived from: i) substances in plasma ii) substances derived from cells 2. Fat absorption: a) absorbs from the digestive tract b) lacteals in the lining of the small intestines and fats enter here and pass to the venous circulation as a milky substance (chyle) 3. Defense: a) lymphocytes are capable of destroying microorganisms and other foreign substances. B. Lymphatic Vessels: 1. They are essential for the maintenance of fluid balance. 2. They begin as small, dead end tubes called lymphatic capillaries 3. In almost all tissues of the body except: a) CNS b) bone marrow c) tissues without blood vessels i) cartilage ii) epidermis iii)cornea 4. They differ from blood capillaries in that they lack a basement membrane and the cells of the simple squamous epithelium slightly overlap and are attached loosely to one another. 5. Lymphatic capillaries join to form lymphatic vessels (have a beaded appearance because of the presence of one-way valves) 6. 3 Factors are responsible for the compression of lymphatic vessels: a) contraction of skeletal muscles during activity b) contraction of the smooth muscles in the lymphatic vessel walls c) pressure changes in the thorax during respiration. 7. Lymph nodes- are round, oval or bean shaped bodies, which function to filter lymph 8. Lymph vessels form lymphatic trunks, which drain a major portion of the body. a) jugular trunk- drains head and neck b) subclavian trunk- drains upper limbs, superficial thoracic wall and mammary glands c) bronchomediastinal trunk- drains the thoracic organs and deep thoracic wall d) intestinal trunk- drains abdominal organs (intestines, stomach, pancreas, spleen, and liver) e) lumbar trunk- drains the lower limbs, pelvic and abdominal walls, pelvic organs, ovaries or testes, kidneys and adrenal glands 9. Lymphatic trunks join with larger vessels (lymphatic ducts) a) on the right, jugular, subclavian and bronchomediastinal trunks join a thoracic vein separately i) 20% of the time, the 3 trunks join together to form right lymphatic duct, they drain the right side of the head, right-upper limbs, and right thorax. ii) right side of body inferior to the thorax and the entire left side drain through the thoracic duct (largest lymphatic vessel) b) sometimes, the lymphatic trunks form a sac (cisterna chyli)

2 10. Figure 22.3 C. Lymphatic Tissue and Organs: 1. Lymphatic organs contain lymphatic tissue which consists primarily of lymphocytes, but also include macrophages, dendritic cells, reticular cells and other cell types. a) lymphocytes- type of WBC; they are part of the immune response that destroys microorganisms and foreign substances. 2. Reticular fibers- are produced by reticular cells 3. Lymphatic organs with a capsule include: a) lymph nodes b) spleen 2

3 c) thymus 4. Mucosa - associated lymphoid tissue (MALT)- is aggregates of non capsulated lymphatic tissue formed in or beneath the mucous membranes lining the digestive, respiratory, urinary, and reproductive tracts. a) include diffuse lymphatic tissue, lymphatic nodes, and the tonsils A. Diffuse Lymphatic Tissue and Lymphatic Nodules: a) diffuse lymphatic tissue- contains dispersed lymphocytes, macrophages, and other cells; no clear boundary, and blends with surrounding tissue i) Figure 22.4 b) lymphatic nodules- are in loose C.T. of the digestive, respiratory, urinary, and reproductive systems i) Peyer's patches- found in the distal half of the small intestines and the appendix ii) found within lymph nodes and the spleen, where they are called lymphatic follicles B. Tonsils: 1. are within the pharynx 2. protection against bacteria and other potentially harmful material 3. three groups of tonsils: a) palatine tonsils- "the tonsils" b) pharyngeal tonsils- adenoids i) can interfere with breathing c) lingual tonsil- on posterior surface of the tongue C. Lymph Nodes: 1. filter the lymph, removing bacteria and other material 2. are categorized as: a) superficial lymph nodes- in the hypodermis beneath skin b) deep lymph nodes- are everywhere else 3. approximately 450 lymph nodes throughout the body 4. cervical and head nodes- (about 70) filter head and neck; axillary nodes (about 30) filter upper limb and superficial thorax; thoracic nodes (about 100) filter the thoracic wall and organs; abdominopelvic nodes (about 230) filter abdomen and pelvis; and inguinal and popliteal nodes (about 20) filter lower limbs and superficial pelvis 5. Figure

4 6. Parts of lymph node: a) capsule b) trabeculae- extension of capsule, internal skeleton c) lymphatic sinuses- in 2 indistinct layers i) outer cortex ii) inner medulla I. cortex consists of a subscapular sinus and cortical sinuses II. inner medulla- organized into branching, irregular strands i) meduallry cords ii) meduallry sinuses * lymph nodes are the only structures to filter lymph d) afferent lymphatic vessels- carry lymph to the lymph node, where it is filtered e) efferent lymphatic vessels- carry lymph away from the nodes f) germinal centers- are areas of rapid lymphocyte division D. Spleen: 1. located on the left side of the superior part of the abdominal cavity 2. it has an outer capsule of dense irregular C.T. and small amount of smooth muscle a) trabeculae- bundles of C.T. fibers from capsule and subdivide organ into small 4

5 compartments filled with: i) white pulp- which is associated with arterial supply (1/4 of vol. of spleen) ii) red pulp- which is associated with the veins (3/4 of vol. of spleen) 3. branches of the splenic artery enter the spleen at the hilum a) Figure the periarterial lymphatic sheath surround arteries and areterioles (supply the red pulp) 5. splenic cords- are a network of reticular cells which produce reticular fibers 6. venous sinuses- connect to trabecular veins, which unite to form vessels that leave the spleen to form the splenic vein. 7. most blood flows through the spleen rapidly, typical of flow with a cloud circulation, in which there is a direct capillary connection between the arterial and venous vessels 5

6 a) most circulation is an open circulation, in which there is no direct capillary connection instead blood empties into the boundaries between the white and red pulp or into the splenic cords. 8. The Spleen: a) destroys defective red blood cells (RBC) b) detects and responds to foreign substances c) acts as a blood reservoir 9. splenectomy- removal of the spleen; liver and other lymphatic tissue are able to compensate for loss E. Thymus: 1. a bilobal gland a) each lobe is surrounded by a thin, C.T. capsule b) trabeculae divide gland into lobules; which is identified as a cortex (outer) and medulla (inner) which also contains thymic corpuscles (Hassall's corpuscles) 2. thymus is site of maturation of certain lymphocytes called T-cells 3. Figure 22.8 II. Immunity: 1. The ability to resist damage from foreign substances 2. Categorized as: a) innate immunity- nonspecific resistance b) adaptive immunity- specific immunity; body recognizes and destroys foreign substances, but the response to them improves each time the foreign substance is encountered i) characteristics: (I) specificity- is the ability to recognize a particular substance (distinguish amoung different kinds of bacteria) (II)memory- is the ability to remember previous encounters with a particular substance and to respond to it more rapidly 6

7 III. Innate Immunity: a) Main components: 1. mechanical mechanisms that prevent the entry of microbes into the body or that physically remove them from body surfaces 2. chemical mediators 3. cells involved in phagocytosis and the production of chemicals that participate in the response of the immune system I. Mechanical Mechanisms: 1. skin and mucous membranes form barriers 2. tears wash substances from eyes 3. substances from mouth by siliva 4. substances from urinary tract by urine 5. by ciliated mucous membranes 6. coughing and sneezing II. Chemical Mediators: a) are molecules responsible for many aspects of innate immunity 1) Table 22.1 b) found on the surface of cells that kill microorganisms or prevent their entry 1. lysozymes 2. sebum 3. mucus c) mediators that promote inflammation by causing vasodialation, increasing vascular permeability, attracting WBC's, and stimulating phagocytosis; interferons, 1. histamine 2. complement 3. prostaglandins 4. leukotriens A. Complement: 1. a group of about 20 proteins that make up approximately 10% of the globulen part of serum a) including proteins named C1-C9 and factors B, D, and P 2. become activated in the complement cascade, a series of reactions in which each complement of the series activates the next a) alternative pathway- is part of the innate immunity and is initiated when complement protein C3 becomes spontaneously active b) classical pathway- is part of the adaptive immune system 3. five of the complement proteins come together to form a membrane attack complex (MAC) which forms a hole in the membrane B. Interferons: 1. are proteins that protect the body against viral infection and perhaps some forms of cancer 2. they neither protect the cell that produces them nor act directly against viruses; they bind to the surface of neighboring cells and stimulate them to produce antiviral proteins C. Cells: a) WBC's and the cells derived from them are the most important cellular components of the immune system 1) Table 22.2 b) chemotatic factors- are parts of microbes or chemicals released by tissue cells that act as chemical signals to attract WBC's i) examples 1. complement 2. leukotrienes 3. kinins 4. histamine ii)chemotaxis- the ability of WBC's to move toward the source of the substances c) phagocytosis- is the endocytosis and destruction of particles by cells (phagocytes). The most important are neutrophils and macrophages (I) Neutrophils: 7

8 1) small phagocytic cells produced in the red bone marrow and released into the blood 2) pass through the gastrointestinal tract and are eliminated in the feces 3) first cells to enter infected tissues 4) pus- is an accumulation of dead neutrophils, dead microorganisms, debris from dead tissue, and fluid (II) Macrophages: 1) are monocytes that leave the blood, enter tissues, and increase their numbers of lysosomes, and mitochondria 2) reticuloendothelial system- the reticular fibers and endothelial lining of sinuses first studied a) macrophages are derived from monocytes i) mononuclear phagocytic system- are monocytes and macrophages with single, unlobed nucleus ii)macrophages with specific names 1) Kupffer cells (liver) 2) microglia (CNS) (III) Basophils, Mast Cells, and Eosinophils: 1) basophils- are derived from red bone marrow, are motile WBC's that can leave the blood and enter infected tissues 2) mast cells- are nonmotile cells in the C.T. 3) eosinophils- enter the blood and enter tissues a) also secrete enzymes that effectively kill some parasites (IV) Natural Killer Cells: 1) are a type of lymphocyte produced in red bone marrow; they recognize classes of cells D. Inflammatory Response: a) is a complex sequence of events involving many of the chemical mediators and cells of innate immunity b) trauma, burns, chemicals, or infections can damage tissues, resulting in inflammation c) chemical mediators produce several effects: 1. vasodilatation 2. chemotactic attraction of phagocytes 3. increased vascular permeability i) fibrinogen is converted to fibrin, which prevents the spread of infection d) inflammation can be: 1. local inflammation- which is an inflammatory response confined to a specific area of the body (a) symptoms: (i) redness (ii) heat (iii) swelling (iv) pain (v) loss of function 2. systemic inflammation- is an inflammatory response that occurs in many parts of the body (a) symptoms (i) local symptoms (ii) red bone marrow produces and releases large numbers of neutrophils (iii) pyrogens- chemicals that stimulate fever production (affect the body's temperature- regulating mechanism (iv) increased vascular permeability- large amounts of fluids are lost from the blood into the tissues (decreased blood volume can cause shock and death) IV. Adaptive Immunity: 1. Involves the ability to recognize, respond to, and remember a particular substance a) antigens- substances that stimulate adaptive immunity (usually large) b) haptens- are small molecules capable of combining with larger molecules to stimulate an adaptive immune system response (i) ex.- penicillin is a hapten that may stimulate an allergic reaction 2. Antigens are divided into 2 groups: a) foreign antigens- are not produced by the body but are introduced from outside it (i) components of bacteria, viruses, etc. (ii) allergic reaction- is an over reaction of the immune system to foreign antigens (pollen, animal 8

9 dander, drugs, etc.) b) self-antigens- are molecules produced by the body that stimulate an adaptive immune system response (can be beneficial or harmful) 3. Adaptive immunity divided into 2 types: a) humoral- when plasma from an immune animal was injected into the blood of a non immune, the non immune become immune b) cell-mediated immunity- when blood cells transferred from an immune animal could be responsible for immunity 4. Immunity results from the activities of lymphocytes (B and T cells) a) B cells- give rise to cells that produce proteins called antibodies (i) Humeral called antibody-mediated immunity (antibodies are responsible) b) T cells- are responsible for cell mediated immunity (i) effector T-cells (cytotoxic T cells) and delayed hypersensitivity T cells are responsible for producing the effects of cell mediated immunity (ii) regulatory T cells (helper T cells and suppressor T cells)- can promote or inhibit the activities of both antibody-mediated immunity and cell-mediated immunity A. Origin and development of Lymphocytes: 1. all blood cells are derived from stem cells in the red bone marrow 2. a positive selection process results in the survival of pre-b and pre-t cells that are capable of an immune response 3. B & T cells that can respond to antigens are composed of small groups of identical lymphocytes called clones 4. negative selection process- eliminates or suppresses clones acting against self-antigens, thereby preventing the destruction of self-cells (i) occurs primarily during prenatal development 5. B cells are released from the red bone marrow; T cells are released from the thymus (i) T-cells to B-cells (5:1) 6) primary lymphatic organs are the sites where lymphocytes mature; these organs are the red bone marrow and thymus 7) secondary lymphatic organs and tissues- are the sites where lymphocytes interact with each other, antigen-presenting cells, and antigens to produce an immune response (i) these include diffuse lymphatic tissue, lymphatic nodules, tonsils, lymph nodes, and the spleen B. Activation of Lymphocytes: a) 2 general principles of lymphocyte activation: 1. lymphocytes must be able to recognize the antigen 2. after recognition, the lymphocytes must increase in number to effectively destroy the antigen I. Antigenic Determinants and Antigen Receptors: 1. antigenic determinants (epitpoes) are specific regions of a given antigen recognized by a lymphocyte and each antigen has many antigenic determinants a) antigen receptors- all the lymphocytes of a given clone have on their surfaces identical proteins which combine with a specific antigenic determinant (similar to lock and key model for enzymes) b) T cell receptor- consists of 2 polypeptide chains, which are subdivided into a variable and a constant region (i) variable area can bind to an antigen c) B-cell receptor- consists of four polypeptide chains with 2 identical variable regions II. Major Histocompatibility Complex Molecules: 1) Most lymphocyte activation involves glycoproteins on the surface of cells (major histocompatibility complex (MHC) molecules) a. They have variable region that can bind to foreign & self-antigens. 2) MHC Class I Molecules found on nucleated cells & function to display antigens produced inside the cells on their surfaces (red flag signal- destroy displaying cell) 3) MHC restricted the cell is displaying a sign that says kill me ; process in which both the antigen & the individual organism s own MHC molecule are required. 4) MHC Class II Molecules are formed on antigen-presenting cells which include B cells, macrophages, monocytes, and dendritic cells (skin-langerhans Cells) a. Use class II molecules to display foreign antigens t other immune system cells 9

10 b. Class II is a rally around the flag signal that stimulates other immune system cells to respond to the antigen. III. Costimulation: 5) The combination of a MHC class II/antigen complex with an antigen receptor is usually only the first signal necessary to produce a response from a B or T cell. a. Cytokines- are proteins or peptides secreted by one cell as a regulator of neighboring cells, promote Costimulation. i. Cytokines produced by lymphocytes are lymphokines. ii. Cytokines are involved in: 1. Regulation of immunity 2. Inflammation 3. tissue repair 4. cell growth 10

11 iii. Table 22.4 iv. CD4- helps T cells (T4 cells) CD8- cytotoxic T cells (T8 cells) a. CD refers to cluster of differentiation which is a system used to clarify many surface molecules. IV. Lymphocyte Proliferation: 6) Exposure to an antigen results in an increase in lymphocyte number a. 1 st there is an increase in the number of helper T cells, which stimulate B or effector T cells. b. 2 nd the number of B or effector T cells increase, which are responsible for the immune response that destroys the antigen. V. Inhibition of Lymphocytes: 7) Tolerance is a state of unresponsiveness of lymphocytes to a specific antigen. a. Most important function is to protect the immune system from responding to self-antigen 8) Tolerance can be induced: a. Deletion of self-reaction lymphocytes b. Preventing activation of lymphocytes i. 2 signals necessary for activation: 1. MHC/antigen complex binding with an antigen receptor 2. Costimulation ii) Preventing activation: 1. Blocking 2. altering 3. deleting an antigen receptor iii) Anergy- means without working is a condition if inactivity in which a B or T cell does not respond to an antigen. c. activation of suppressor T cells i. suppressor T cells are a group of T cells that are defined by their ability to suppress immune responses. VI. Antibody-Mediated Immunity: 9) Exposure of the body to an antigen can lead to activation of B cells & to production of antibodies, which are responsible for destructions of the antigens. 10) It is effective against extracellular antibodies. (bacteria, viruses, protozoans, fungi, parasites & toxins outside the cell) 11) Can also cause immediate hypersensitivity reactions 11

12 A. Antibodies a. are proteins produced in response to an antigen b. on the basis of protein type & associated lipids, plasma proteins are separated into: i. albumin ii. alpha iii. beta globins iv. gamma c. as a group, antibodies are sometimes called gamma globulin because they are mostly found in the Y-globulin part of plasma; also called immunoglobulins; 5 classes i. IgG ii. IgM iii. IgA iv. IgE v. IgD d. All classes of antibodies have similar structure (4polypeptide chains) i. Variable region- is the part that combines with the antigenic determinant of the antigen. ii. Constant region- is the rest of the antibody which is responsible for activities of antibodies e. Figure f. Table

13 I. Effects of Antibodies a. Affect antigens in 2 ways: 1) antibody can bind to the antigenic determinant & interfere with the ability of the antigen to function 2) the antibody can combine with the antigenic determinant on 2 different antigens, rendering the antigens in effective b. ability of antibodies to join antigens together is the basis for many clinical tests (blood typing) c. Opsonins- are substances that make an antigen more susceptible to phagocytosis 13

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16 II. Antibody Production: 1) Primary response- results from the first exposure of a B cell to an antigen for which it is specific & includes a series of cell division, cell differentiation, & antibody production. a. Plasma cells- produce antibodies b. Memory B cells- enlarge cells that revert back to small lymphocytes. c. IgM is usually the 1 st antibody produced in response to an antigen; primary response normally takes 3-14 days to produce enough antibodies to be effective. 2) Secondary (memory) response- occurs when the immune system is exposed to an antigen against which it has already produced a primary response. a. Provides better protection than the primary response for 2 reasons: i. Time required to start producing antibodies is less ii. The amount of antibody produced is much larger b. Memory response also includes the formation of new memory B cells, which provide protection against additional exposures. c. Memory B cells are the basis for adaptive immunity. VII. Cell-Mediated Immunity: 1) Is a function of T cells and is most effective against intracellular microorganisms (viruses, fungi, intracellular bacteria, & parasites) 2) Figure VIII. IX. 3) Effector T cells are responsible for the cell-mediated immunity response 4) Memory T cells can provide a secondary response & long testing immunity ii. Cytotoxic T Cells: a. Have 2 main effects: 1. the lyse cells 2. they produce cytokines b. The major method of lysis involves a protein called perforin, which forms a pore in the membrane of the target cell. iii. Delayed Hypersensitivity T Cells: a. Respond to antigens by releasing cytokines; they promote phagocytosis and inflammation, especially in allergic reactions. b. Poison ivy antigens can be processed by Langerhans cells in the skin Immune Interactions: c. Immune system responses of ten involve components of more than one type of immunity. Immunotherapy: 1) Treats disease by altering immune system function or by directly attacking harmful cells. 2) If an antigen unique to tumor cells can be found, then monoclonal antibodies could be used to deliver: a. Radioactive isotopes b. Drugs 16

17 c. Toxins d. Enzymes e. Cytokines a. One problem with monoclonal antibody delivery system is that the immune system recognizes the monoclonal antibody as a foreign antigen, and it is rendered in effective. i. Humanization- is a process where the monoclonal antibodies are modified to resemble human antibodies ii. 131 I is a monoclonal antibody with radioactive iodine used for B-cell lymphoma. iii. Herceptin is a monoclonal antibody that binds to a growth factor of primary breast cancer. X. Acquired Immunity: a. Its possible to acquire adaptive immunity in 4 ways: 1. active natural 2. active artificial 3. passive natural 4. passive artificial i. natural & artificial refer to method of exposure b. Natural exposure implies that contact with an antigen or antibody occurs as part of everyday living. c. Artificial exposure (immunization) - is a deliberate introduction of an antigen or antibody in to the body. i. Active and passive indicate whether or not an individual s immune system is directly responding to the antigen. d. Active immunity- individual s own immune system is the cause of the immunity because of natural or artificial exposure. e. Passive immunity- occurs when another person or animal develops antibodies and the antibodies are transferred to a non immune individual. A. Active Natural Immunity: 1. Natural exposure to an antigen can cause an individuals immune system to mount an adaptive immune system response and achieve active natural immunity. B. Active Artificial Immunity: 1. An antigen is deliberately introduced into an individual to stimulate the immune system via vaccination; the introduced antigen is a vaccine. i. Example DTP injection against diphtheria, tetanus, & pertussis (whooping cough) & the MMR injection against mumps, measles, & rubella (German measles). C. Passive Natural Immunity: 1. Results from the transfer of antibodies from a mother to her child across the placenta before birth. a. Antibodies are IgG b. Antibodies IgA are provided while nursing. D. Passive Artificial Immunity: 1. Usually begins with vaccinating an animal (horse); antibodies are removed & injected into the individual requiring immunity. 2. This technique is only temporary XI. Effects on Aging: 5) Appears to have little effect on the ability of the lymphatic system to remove fluid from tissues, absorb fats from the digestive tract, or remove defective RBC s from the blood. 6) Primary & secondary antibody responses decrease with age. 7) The ability of cell-mediated immunity to resist intracellular pathogens decreases with age. 17

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