Saladin 5e Extended Outline

Chapter 21 The Lymphatic and Immune Systems

I. The Lymphatic System (pp. 816 82!" A. The lymphatic system is composed of a network of vessels that penetrate nearly every tissue, and a collection of tissues and organs that produce immune cells. (p. 816) ( ig. !1.1) ". The lymphatic system has three functions. (p. 816) 1. luid recovery. luid continually filters from #lood capillaries into tissue spaces, and the lymphatic system rea#sor#s any e$cess and return it to the #lood. a. The #lood capillaries rea#sor# a#out 8%& of fluid, leaving 1%& e$tra. #. This amounts to ! to ' ( of water and ) to * of the plasma protein+ a person would die within hours if this were not returned via the lymph system. c. ,ven partial interference with lymphatic drainage can lead to severe edema. ( ig. !1.!) !. -mmunity. The lymphatic system also picks up foreign cells and chemicals from tissues. a. The fluid passes through lymph nodes where immune cells stand guard. #. These cells activate a protective immune response. .. (ipid a#sorption. -n the small intestine, special lymphatic vessels called lacteals a#sor# dietary lipids not a#sor#ed #y #lood capillaries. /. The components of the lymphatic system are lymph, lymphatic vessels, lymphatic tissue, and lymphatic organs. (p. 816) 0. (ymph is a clear, colorless fluid, similar to #lood plasma #ut low in protein, that originates as tissue fluid taken up #y the lymphatic vessels. (pp. 81818!2) 1. The composition of lymph varies from place to place and at different times. !. (ymph leaving the lymph nodes contains a large num#er of lymphocytes and may also contain macrophages, hormones, #acteria, viruses, cellular de#ris, or even cancer cells. .. (ymphatic vessels are similar to #lood vessels. a. The vessels #egin with microscopic lymphatic capillaries (terminal lymphatics)+ these are present almost everywhere #ut are a#sent from the /34, cartilage, cornea, #one, and #one marrow. #. They are closely associated with #lood capillaries, #ut are closed at one end. ( ig. !1..)

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c. A lymphatic capillary consists of a sac of thin endothelial cells that overlap like shingles of a roof. i. They are tethered to surrounding tissue #y protein filaments that prevent the sac from collapsing. d. (ymphatic endothelial cells are not 7oined #y tight 7unctions and do not have a continuous #asal lamina+ thus cells and particles can enter with the fluid. e. The overlapping edges of the endothelial cells act as valvelike flaps that can open and close in response to tissue pressure. f. (ymphatic vessels form in the em#ryo #y #udding from veins, and the larger ones have a similar histology. i. A tunica interna has an endothelium and valves. ( ig. !1.') ii. A tunica media has elastic fi#ers and smooth muscle. iii. A tunica e$terna is the thin outermost layer. g. The lymphatic vessels converge and #ecome larger vessels with changing names8 lymphatic capillaries collecting vessels si$ lymphatic trunks two collecting ducts su#clavian veins. ( ig. !1.%) h. The lymphatic capillaries converge to form collecting vessels. i. These vessels often travel alongside veins and arteries and share a common connective tissue sheath with them. i. /ollecting vessels empty into lymph nodes at irregular intervals+ lymph leaves the nodes through another collecting vessel and may continue through several nodes. 7. ,ventually the collecting vessels converge to form larger lymphatic trunks, each of which drains a ma7or portion of the #ody. i. The si$ lymphatic trunks are named #y their locations and the parts of the #ody they drain8 7ugular, su#clavian, #ronchomediastinal, intercostal, intestinal, and lum#ar. k. The lymphatic trunks converge to form the two collecting ducts, the largest of the lymphatic vessels. ( ig. !1.6) i. The right lymphatic duct is formed #y the convergence of the right 7ugular, su#clavian, and #ronchomediastinal trunks in the right thoracic cavity+ it drains the right arm, right side of the thora$, and head, and it empties into the right su#clavian vein. ii. the thoracic duct, on the left, is larger and longer, #eginning 7ust #elow the diaphragm anterior to the verte#ral column near (!.

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iii. The two lum#ar trunks and the intestinal trunk 7oin to form a prominent sac called the cisterna chyli, names for the large amount of chyle (fatty lymph) that it collects after a meal. iv. The thoracic duct than passes upward through the diaphragm with the aorta and ascend the mediastinum+ as it passes through the thora$, it connects with the left #ronchomediastinal, left su#clavian, and left 7ugular trunks, then empties into the left su#clavian vein.

'. low of lymph is governed #y forces similar to those for venous return, e$cept that the lymphatic system has no pump like the heart, and lymph flows at an even lower pressure and speed compared to venous #lood. a. The primary mechanism of flow is rhythmic contractions of the lymphatic vessels themselves in response to distention. #. The valves of lymphatic vessels prevent fluid from flowing #ackward. c. (ymph flow is also produced #y skeletal muscles s9uee:ing the lymphatic vessels. d. "ecause lymphatic vessels are often ne$t to an artery inside a common sheath, arterial pulsation may also contri#ute to lymph flow. e. A thoracic (respiratory) pump promotes the flow of lymph from the a#dominal to the thoracic cavity as one inhales. f. At the point where the ducts empty into the su#clavian veins, the rapidly flowing #loodstream draws the lymph into it. g. 6hysical e$ercise significantly increases the rate of lymphatic return. ,. (ymphatic cells range from loosely scattered cells in different tracts to compact populations in lymphatic organs+ a variety of lymphocytes and other cells have roles in immunity. (pp. 8!218!!) 1. 3atural killer (3;) cells are large lymphocytes that attack and destroy #acteria, transplanted tissue cells, and host cells that are infected with virus or have turned cancerous. !. T lymphocytes (T cells) mature in the thymus and later depend on thymic hormones+ the T stands for thymus<dependent. .. " lymphocytes (" cells) are lymphocytes that mature in the #one marrow and differentiate into plasma cells that secrete the anti#odies of the immune system. '. =acrophages are very large, avidly phagocytotic cells of the connective tissues+ they develop from monocytes that have emigrated from the #loodstream and phagocyti:e tissue de#ris, dead neutrophils, #acteria, and other foreign matter. ( ig. !1.>) a. They also process foreign matter and display antigenic fragments of it on their surface to alert certain T cells of a foreign presence+ cells that do this are collectively termed antigen<presenting cells (A6/s).

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%. 0endritic cells are #ranched, mo#ile A6/s found in the epidermis, mucous

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mem#ranes, and lymphatic organs+ in the skin they are often called (angerhans cells. a. They help alert the immune system to pathogens that have #reached #ody surfaces. #. They engulf foreign matter #y receptor<mediated endocytosis rather than phagocytosis and are included in the macrophage system. 6. ?eticular cells are #ranched stationary cells that contri#ute to the stroma of lymphatic organs and act as A6/s in the thymus+ they should not #e confused with reticular fi#ers. ( ig. !1.12) . (ymphatic (lymphoid) tissues are aggregations of lymphocytes in the connective tissues of mucous mem#ranes and various organs. (p. 8!!) 1. 0iffuse lymphatic tissue has lymphocytes scattered rather than densely clustered and is prevalent in #ody passages open to the e$terior (respiratory, digestive, etc.) where it is called mucosa<associated lymphatic tissue (=A(T). a. -n the respiratory and digestive tracts is it sometimes called #ronchus< associated ("A(T) and gut<associated (@A(T) lymphatic tissue. !. -n some places, lymphocytes and macrophages congregate in dense masses called lymphatic nodules (follicles). ( ig. !1.8) a. These come and go as pathogens invade tissues and are dealt with. #. A#undant lymphatic nodules are a relatively constant feature of the lymph nodes, tonsils, and appendi$. c. -n the ileum, they form clusters called 6eyer patches. @. (ymphatic (lymphoid) organs have well<defined anatomical sites and at least partial connective tissue capsules that separate lymphatic tissue from neigh#oring tissue. (pp. 8!!18!8) 1. These organs include the red #one marrow, thymus, lymph nodes, tonsils, and spleen. !. ?ed #one marrow and thymus are regarded as primary lymphatic organs #ecause they are sites where " and T lymphocytes #ecome immunocompetent. .. (ymph nodes, tonsils, and spleen are called secondary lymphatic organs #ecause they are populated with immunocompetent lymphocytes only after the cells have matured in the primary organs. '. ?ed #one marrow is involved in hemopoiesis (#lood formation) and immunity. a. -n children, red #one marrow occupies the medullary spaces of nearly the entire skeleton, whereas in adults, it is limited to parts of the a$ial skeleton and the pro$imal heads of the humerus and femur. #. ?ed #one marrow is a soft, loosely organi:ed, highly vascular material separated from osseous tissue #y the endosteum.

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c. -t produces all classes of formed elements of the #lood, and its red color is from the a#undance of erythrocytes. d. 3umerous arteries penetrate the #one via nutrient foramina and empty into large sinusoids in the marrow. ( ig. !1.A) e. The sinusoids drain into a central longitudinal vein that e$its via the same foramina. f. The sinusoids are lined #y endothelial cells, like other #lood vessels, and are surrounded #y reticular cells and reticular fi#ers. i. The reticular cells secrete colony<stimulating factors that induce formation of leukocytes. ii. -n the long #ones, aging reticular cells accumulate fat and transform into adipose cells, eventually replacing red #one marrow with yellow #one marrow. g. The spaces #etween the sinusoids are occupied #y islands (cords) of hemopoietic cellsBmacrophages and #lood cells in all stages of development. i. The macrophages destroy malformed #lood cells and nuclei discarded #y developing erythrocytes. ii. As #lood cells mature, they push their way through the reticular and endothelial cells to enter the sinus and the #loodstream.

%. The thymus is a mem#er of the endocrine, lymphatic, and immune systems. a. -t houses developing lymphocytes and secretes hormones that regulate their later activity. #. -t is a #ilo#ed organ located #etween the sternum and aortic arch in the superior mediastinum+ it degenerates with age as descri#ed earlier. ( ig. 1>.8) c. The fi#rous capsule of the thymus give off tra#eculae (septa) that divide the gland into several angular lo#ules. i. ,ach lo#ule has a dense, dark<staining corte$ and a lighter medulla populated #y T lymphocytes. ( ig. !1.12) ii. ?eticular epithelial cells seal off the corte$ from the medulla and surround #lood vessels and lymphocyte clusters, forming the #lood1 thymus #arrier that isolates developing lymphocytes from #lood<#orne antigens. d. After developing in the corte$, the T cells migrate to the medulla, where they spend another . weeks. i. There is no #lood1thymus #arrier in the medulla+ mature T cells enter #lood or lymphatic vessels and leave the thymus.

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ii. -n the medulla, the reticular epithelial cells form whorls called thymic (Cassall) corpuscles, useful for identifying the thymus histologically. e. ?eticular epithelial cells also produce signaling molecules that promote development and action of T cells, including thymosin, thymopoietin, thymulin, interleukins, and interferon. f. -f the thymus is removed from new#orn mammals, they waste away and never develop immunity. g. 5ther lymphatic organs depend on thymosins or T cells and develop poorly in thymectomi:ed animals.

6. (ymph nodes are the most numerous lymphatic organs, num#ering a#out '%2 in a typical young adult. ( ig. !1.11) a. They serve to functions8 cleansing the lymph, and acting as a site of T and " cell activation. #. A lymph node is an elongated or #ean<shaped structure, usually less than . cm long, often with an indentation called the hilum on one side. ( ig. !1.1!) i. -t is enclosed in a fi#rous capsule with tra#eculae that partially divide the interior into compartments. ii. "etween the capsule and parenchyma is a narrow, relatively clear space called the su#capsular sinus, which contains reticular fi#ers, macrophages, and dendritic cells. iii. 0eep to this sinus the gland consists mainly of a stroma of reticular connective tissue and a parenchyma of lymphocytes and A6/s. c. The parenchyma is divided into an outer /<shaped corte$ that encircles a#out 'D% of the organ and an inner medulla that e$tends to the surface at the hilum. i. The corte$ consists of lymphatic nodules that ac9uire germinal centers for " cell multiplication when the lymph node is fighting a pathogen. ii. The medulla consists of a #ranching network of medullary cords composed of lymphocytes, plasma cells, macrophages, reticular cells, and reticular fi#ers. iii. "oth regions also contain lymph<filled sinuses continuous with the su#capsular sinus. d. Afferent lymphatic vessels lead into a node along its conve$ surface. i. (ymph flows from these vessels into the su#capsular sinus and percolates slowly through the sinuses of the corte$ and medulla.

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e. The lymph leaves the node through one to three efferent lymphatic vessels that emerge from the hilum. f. 3o other lymphatic organs have afferent lymphatic vessels, and lymph nodes are the only organs that filter lymph. i. =acrophages and reticular cells of the sinuses remove a#out AA& of the impurities #efore lymph leaves the node. ii. 4e9uential passage through a num#er of nodes thoroughly cleanses the lymph #efore it returns to the #lood. g. "lood vessels also penetrate the hilum of a lymph node. i. Arteries follow the medullary cords and give rise to capillary #eds in the medulla and corte$. ii. -n the deep corte$, lymphocytes can emigrate from the #loodstream into the parenchyma of the node+ most are T cells. h. (ymph nodes are widespread, #ut especially concentrated in seven locations. ( ig. !1.1) i. /ervical lymph nodes occur in deep and superficial groups in the neck, monitoring lymph coming from the head and neck. ii. A$illary lymph nodes are concentrated in the armpit and receive lymph from the upper lim# and the female #reast. ( ig. !1.6#) iii. Thoracic lymph nodes occur in the thoracic cavity, especially em#edded in the mediastium. iv. A#dominal lymph nodes occur in the posterior a#dominopelvic wall and monitor lymph from the urinary and reproductive system. v. -ntestinal and mesenteric lymph nodes are found in the mesenteries and ad7acent to the appendi$ and intestines. ( ig. !1.11a) vi. -nguinal lymph nodes occur in the groin and receive lymph from the entire lower lim#. ( ig. !1.1#) vii. 6opliteal lymph nodes occur at the #ack of the knee and receive lymph from the leg proper. i. Ehen a lymph node is challenged #y a foreign antigen, it may #ecome swollen and painful, a condition called lymphadenitis. 7. The collective term for all lymph node diseases is lymphadenopathy. k. (ymph nodes are common sites of metastatic cancer.

Insight 21.1 (ymph 3odes and =etastatic /ancer >. Tonsils are patches of lymphatic tissue located at the entrance to the pharyn$, where they guard against ingested and inhales pathogens.

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a. ,ach is covered #y epithelium and has deep pits called tonsillar crypts lined #y lymphatic nodules. ( ig. !1.1.) #. "elow the crypts, the tonsils are partially separated from underlying connective tissue #y an incomplete fi#rous capsule. c. There are three main sets of tonsils. i. A single medial pharyngeal tonsil (adenoids) is located on the wall of the pharyn$ 7ust #ehind the nasal cavity. ii. A pair of palatine tonsils is at the posterior margin of the oral cavity. iii. 3umerous lingual tonsils, each with a single crypt, are concentrated in a patch on each side of the root of the tongue. ( ig. !%.%a) d. The palatine tonsils are largest and most often infected in tonsillitis, an acute inflammation usually caused #y a Streptococcus infection. i. 4urgical removal (tonsillectomy) used to #e a common surgical procedure in children #ut is done less often today. ii. Tonsillitis is now usually treated with anti#iotics.

8. The spleen is the largest lymphatic organ, up to 1! cm long and 162 g+ it is located in the left hypochondriac region inferior to the diaphragm and posterolateral to the stomach. ( ig. !1.1') a. The spleen has indentations called the gastric area and the renal area where it presses against these organs, and a medial hilum penetrated #y the splenic artery, splenic vein, and lymphatic vessels. #. The parenchyma e$hi#its two types of tissue reflecting its functions. i. ?ed pulp consists of sinuses containing erythrocytes. ii. Ehite pulp consists of lymphocytes and macrophages aggregated along small #ranches of the splenic artery+ it appears in sections as an ovoid mass of lymphocytes with an arteriole passing through. c. The spleen produces #lood cells in the fetus and may resume this role in adults in the event of severe anemia. d. (ymphocytes and macrophages of the white pulp monitor the #lood for foreign antigens, much like the lymph nodes do for the lymph. e. 4plenic capillaries are permea#le and allow ?"/s to leave the #loodstream, accumulate in the sinuses of red pulp, and reeneter the #loodstream later. i. 5ld, fragile ?"/s rupture as they s9uee:e through into the sinuses and are phatocyti:ed #y macrophages+ thus the spleen is an Ferythrocyte graveyard.G ii. The spleen also helps to sta#ili:e #lood volume #y transferring e$cess plasma to the lymphatic system.

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f. The spleen is highly vascular and vulnera#le to trauma and infection.

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i. A ruptured spleen can hemorrhage fatally, #ut is difficult to repair. ii. 4plenectomy is a common procedure in such cases+ a person can live without a spleen #ut is somewhat more vulnera#le to infections. II. #$nspeci%ic &esistance (pp. 82! 8'(" A. 6athogens are environmental agents capa#le of producing disease+ this includes infectious organisms, to$ic chemicals, and radiation. (p. 8!A) ". The human #ody has three lines of defense against pathogens. (p. 8!A) 1. The first line of defense consists of e$ternal #arriers, such as the skin and mucous mem#ranes. !. The second line of defense consists of nonspecific mechanisms to deal with pathogens that #reak through the skin or mucous mem#ranes. a. These include leukocytes and macrophages, antimicro#ial proteins, immune surveillance, inflammation, and fever. #. These mechanisms are present from #irth and are #roadly effective against many pathogens+ they even work against pathogens to which the #ody has never #een e$posed. .. The third line of defense is the immune system, which defeats and pathogen and retains a FmemoryG of it to guard against future encounters. '. The first two are called nonspecific resistance+ immunity is called a specific defense. /. The first line of defense is the e$ternal #arrier presented #y the skin and mucous mem#ranes. (pp. 8!A18.2) 1. The surface of skin is composed mainly of keratin, a tough protein. a. Eith some e$ceptions the skin is dry and poor in nutrients and is therefore hostile to micro#ial reproduction. #. -t is also coated with antimicro#ial chemicals such as defensins and lactic acid. i. 0efensins are peptides that kill micro#es #y creating holes in their mem#ranes. ii. (actic acid makes up the acid mantle, which is generated #y sweat and inhi#its #acterial growth. !. The digestive, respiratory, urinary, and reproductive tracts are open to the e$terior, and are protected #y mucous mem#ranes. a. =ucus physically ensnares micro#es. i. -n the respiratory tract, cilia move the mucus to the pharyn$ to #e eliminated. ii. =icro#es are flushed from the upper digestive tract #y saliva.

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iii. Hrine flushes micro#es from the lower urinary tract.

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#. =ucus, tears, and saliva contain lyso:yme, and en:yme that dissolved #acterial cell walls. .. "eneath the epithelia of the skin and mucous mem#ranes is a layer of areolar tissue. a. The ground su#stance of this tissue contains a giant glycosaminoglycan called hyaluronic acid, a gel<like su#stance through which it is difficult for micro#es to penetrate. i. 4ome organisms produce hyaluronidase that #reaks down the hyaluronic acid. ii. Cyaluronidase occurs in some snake venoms and #acterial to$ins as well as some parasitic proto:oans. 0. (eukocytes and macrophages attack micro#es that get past the physical #arriers. (pp. >6'1>66) 1. ive types of leukocytes (Ta#le 18.>) make individual contri#utions to resistance and immunity. a. 3eutrophils wander in connective tissues killing #acteria. i. They engulf and digest #acteria and also release #actericidal chemicals. ii. Ehen #acteria are detected, neutrophilsI lysosomes migrate to the surface and degranulate, or discharge en:ymes into the tissue fluid. iii. 5ne en:yme cataly:es the respiratory #urst, in which o$ygen is reduced to supero$ide anions (5!J1) that react with CK to form hydrogen pero$ide (C!5!). iv. Another en:yme produces hypochlorite (C/l5). v. These to$ic chemicals form a killing :one around the neutrophil, which kills the neutrophil as well as the micro#es. #. ,osinophils are found especially in mucous mem#ranes where they guard against parasites, allergens, and other pathogens. i. They #ecome concentrated at sites of allergy, inflammation, or parasitic infection. ii. They help to kill tapeworms and roundworms #y producing supero$ide, hydrogen pero$ide, and to$ic proteins. iii. They promote the action of #asophils and mast cells. iv. They phagocyti:e and degrade antigen1anti#ody comple$es. v. They secrete en:ymes that limit the action of histamine and other inflammatory chemicals. c. "asophils secrete chemicals that aid the mo#ility and action of other leukocytes.

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i. (eukotrienes activate and attract neutrophils and eosinophils. ii. Cistamine, a vasodilator, increases #lood flow and delivery of leukocytes. iii. Ceparin inhi#its clotting. iv. =ast cells, a type of connective tissue cell very similar to #asophils, also produce these su#stances. d. (ymphocytes appear similar, #ut several different functional types are distinguished. i. Three #asic categories are 3; cells (%& of lymphocytes), T cells (82& of lymphocytes), and " cells (1%& of lymphocytes). ii. These have roles in immune surveillance and specific immunity. e. =onocytes are leukocytes that emigrate from #lood into connective tissues and transform into macrophages. i. All avidly phagocytotic cells e$cept leukocytes are called the macrophage system. ii. 0endritic cells are included in this system even though they come from different stem cells than macrophages and employ receptor< mediated endocytosis. iii. =acrophages are widely distri#uted in loose connective tissues (histiocytes). iv. =icroglia are speciali:ed macrophages of the /34. v. Alveolar macrophages are specific to the lungs. vi. Cepatic macrophages are specific to the liver.

,. =any types of proteins play a role in nonspecific resistance+ two families of antimicro#ial proteins descri#ed here are interferons and the complement system. (pp. 8.118.!) 1. -nterferons are secreted #y certain cells, especially leukocytes, that are infected with viruses. a. -nterferons alert neigh#oring cells and protect them from #ecoming infected. #. -nterferons #ind to surface receptors and activate second<messenger systems that lead to synthesis of proteins that defend against virus infection. c. They also activate 3; cells and macrophages that destroy infected cells. d. They may confer resistance to cancer cells as well. !. The complement system is a group of .2 or more glo#ulins that contri#ute to #oth nonspecific resistance and specific immunity. a. /omplement proteins are synthesi:ed mainly #y the liver and circulate in the #lood in inactive form+ they are activated in the presence of pathogens.

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#. -n their inactive form, the proteins are named with the letter / and a num#er (/.)+ activation splits them into fragments, which are identified #y lowercase letters (/.a, /.#) c. Activated complement #rings a#out four methods of pathogen destruction8 inflammation, immune clearance, phagocytosis, and cytoloysis. d. There are three routes to complement activation8 The classical, alternative, and lectin pathways. ( ig. !1.1%) e. The classical pathway re9uires an anti#ody molecule to get started and thus is a part of specific immunity. i. The anti#ody #inds to an antigen on the surface of a pathogenic organism, forming and antigen1anti#ody (Ag1A#) comple$. ii. This #inding changes the anti#odyIs shape, e$posing two complement<#inding sites. ( ig. !1.!>a) iii. "inding of the first complement (/1) to these sites sets off a reaction cascade in an amplifying process+ this is called complement fi$ation. f. The alternative and lectin pathways re9uire no anti#odies and thus #elong to nonspecific resistance. g. /omplement /. slowly and spontaneously #reaks down in the #lood into /.a and /.#. h. -n the alternative pathway, /.# #inds directly to targets such as human tumor cells, viruses, #acteria, and yeasts, triggering a reaction cascade. i. -n this case the cascade has an autocatalytic effect. ii. /.# eventually leads to the accelerated splitting of more /. and production of more /.#. i. (ectins are plasma proteins that #ind to car#ohydrates+ in the lectin pathway, a lectin #inds to certain sugars of a micro#ial cell surface and sets off a reaction cascade leading to /.# production.

.. The splitting of /. into /.a and /.# is where all activation pathways of the complement system converge+ the end results produced #y these fragments are as follows. ( ig. !1.1%) a. -nflammation. i. /.a stimulates mast cells and #asophils to secrete histamine and other inflammatory chemicals. ii. -t also activates and attracts neutrophils and macrophages. #. -mmune clearance. i. /.# #inds Ag1A# comple$es to ?"/s.

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ii. As these ?"/s circulate through the liver and spleen, macrophages strip of and destroy the comple$es, leaving the ?"/s unharmed. c. 6hatocytosis. i. "acteria, viruses, and other pathogens are phagocyti:ed and digested #y neutrophils and macrophages, #ut they cannot internali:e FnakedG microorganisms. ii. /.# coats micro#ial cells and serves as #inding sites for phagocyte attachment, a process called opsoni:ation. d. /ytolysis. i. /.# splits another complement protein, /%, into /%a and /%#. ii. /%a 7oins /.a in its proinflammatory actions. iii. /%# #inds to an enemy cell and attracts complements /6, />, and /8. iv. This conglomeration (/%#6>8) #inds up to 1> molecules of /A, forming a ring called the mem#rane attack comple$. ( ig. !1.16) v. This comple$ forms a hole in the target cell, leading to cell rupture.

. -mmune surveillance is a phenomenon in which 3; cells patrol the #ody looking for pathogens or diseased cells to attack. (pp. 8.!18..) 1. Hpon recognition of an enemy cell, the 3; cell #inds to it and releases proteins called perforins. a. The perforins polymeri:e in a ring and create a hole in the enemy cellIs plasma mem#rane. ( ig. !1.1>) #. This hole allows water and salts to flow into the cell, possi#ly killing it. !. The 3; cell also secretes protein<degrading en:ymes called gran:ymes, which enter the pore made #y the perforins+ these destroy cellular en:ymes and induce apoptosis. @. ever is an a#normal elevation of #ody temperature also known as pyre$ia+ fe#rile means pertaining to fever. (pp. 8..18.') 1. ever can result from trauma, infections, drug reactions, #rain tumors, and other causes+ natural variations in #ody temperature make defining a fever an individual matter. !. ever was long considered an undesira#le side effect, #ut it is now recogni:ed as an adaptive defense that can do more good than harm. .. Antipyretic (fever<reducing) medications such as aspirin can sometime prolong illness, as in colds. '. ever is #eneficial in that it (1) promotes interferon activity, (!) elevates meta#olic rate and accelerates tissue repair, (.) inhi#its reproduction of #acteria and viruses. %. ever is typically initiated #y e$ogenous pyrogens (fever<producing agents) such as the surface glycolipids of #acteria and viruses.

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a. As neutrophils and macrophages attack pathogens, they secrete endogenous pyrogensBinterleukins, interferons, and other chemicals. #. These chemicals stimulate neurons in the anterior hypothalamus to secrete prostaglandin ,! (6@,!). c. 6@,! in turn raises the hypothalamic set point for #ody temperature. ( ig. !1.18) d. Aspirin and i#uprofen reduce fever #y inhi#iting prostaglandin synthesis, #ut using aspirin for this purpose may have deadly conse9uences.

Insight 21.2 ?eye 4yndrome e. Ehen the set point rises, a person shivers to generate heat and the cutaneous #lood vessels constrict to reduce heat loss. i. -n fever onset, one has chills, feels cold and clammy, and has a rising temperature. ii. -n the ne$t stage, stadium, the #ody temperature oscillates around the new set point+ the liver and spleen hoard :inc and iron, depriving #acteria of minerals needed for reproduction. iii. Ehen the infection is defeated, the hypothalamic setpoint is returned to normal, and temperature drops in the phase called defervescence, crisis (if a#rupt), or lysis (if falling slowly). 6. ,$cessively high temperature can #e dangerous #ecause of meta#olic discoordination and cellular dysfunction. a. evers a#ove '2.%L/ (12%L ) can make a person delirious. #. /onvulsions and coma ensue at higher temperatures, and death or irreversi#le #rain damage can result from fevers of ''L to '6L/ (111L to 11%L ). C. -nflammation is a local defensive response to tissue in7ury of any kind. (pp. 8.'18.>) 1. -t has three general purposes8 a. To limit the spread of pathogens and ultimately destroy them. #. To remove the de#ris of damaged tissue. c. To initiate tissue repair. !. -nflammation is characteri:ed #y four cardinal signs8 redness, swelling, heat, and pain. .. Eords ending in the suffi$ <itis denote inflammation of specific organs and tissues, as in arthritis, peritonitis, etc. '. -nflammation is most common and o#serva#le in the skin, #ecause it is su#7ect to more trauma than any other organ. %. -nflammatory process are mediated #y several types of cells and chemicals, summari:ed in Ta#le !1.1.

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6. =any of the chemicals are in the class called cytokinesBsmall proteins secreted #y leukocytes that alter physiology or #ehavior of receptor cells. a. /ytokines usually act at short range, on neigh#oring cells (paracrine effects) or on the same cell that secretes them (autocrine effects). #. cytokines include interferons, interleukins, tumor necrosis factor, chemotactic factors, and others. >. -nflammation involved three ma7or processes8 mo#ili:ation of defenses, containment and destruction of pathogens, and tissue cleanup and repair. 8. =o#ili:ation of defenses is the most immediate re9uirement. a. (ocal hyperemia, increasing #lood flow #eyond its normal rate, is a 9uick way to get defensive leukocytes to the scene. #. /ertain cells secrete vasoactive chemicals, among them histamine, leukotrienes, and other cytokines. i. These are secreted #y #asophils of the #lood, mast cells of connective tissue, and cells damaged #y the trauma, to$ins, or organisms. ii. Cyperemia also helps flush to$ins and wastes from the tissues. c. Masoactive chemicals also stimulate endothelial cells of the #lood capillaries to separate slightly, increasing capillary permea#ility to fluid, leukocytes, and plasma proteins. i. These protein include complement, anti#odies, and clotting proteins. d. ,ndothelial cells of the #lood vessels actively recruit leukoctyes. i. -n the area of in7ury, they produce cell<adhesion molecules called selectins, which make their mem#ranes sticky and snag leukocytes, a process called margination. ii. The leukocytes adhere loosely, sometimes coating the endothelium so thickly that they o#struct #lood flow. iii. The leukocytes then crawl through the gaps #etween endothelial cells, an action called diapedesis or emigrationBand thus enter the tissue fluid. ( ig. !1.1A) iv. /ells and chemicals that have left the #loodstream are said to #e e$travasated. e. The #asis of the four cardinal signs of inflammation occurs in these events. i. The heat results from the hyperemia. ii. ?edness is also due to hyperemia, and in cases such as sun#urn, to e$travasated erythrocytes in the tissue. iii. 4welling is due to increased fluid filtration from the capillaries.

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iv. 6ain results from direct in7ury to nerves, pressure on the nerves from edema, and stimulation of pain receptors #y prostaglandins, to$ins of some #acteria, and #radykinin, an eicosanoid.

A. /ontainment and destruction of pathogens protects the rest of the #ody. a. i#rinogen that filters into the tissue fluid clots in areas ad7acent to the in7ury, se9uestering #acteria and other micro#es. #. Ceparin prevents clotting in the area of the in7ury itself, so #acteria and other pathogens are essentially trapped in a fluid pocket surrounded #y a capsule of clotted fluid. c. The trapped pathogens are attacked #y phagocytes, anti#odies, and other defenses. d. 3eutrophils are the chief enemies of #acteria+ they accumulate within an hour of in7ury. i. After emigrating from the #loodstream, they e$hi#it chemota$isB attraction to chemicals such as #radykinin and leukotrienes that guide them to the in7ury or infection site. ii. Hpon encountering #acteria, the neutrophils avidly phagocyti:e and digest them, and destroy many #y means of the respiratory #urst. iii. 3eutrophils also recruit macrophages and additional neutrophiles #y secreting cytokines themselves. e. Activated macrophages and T cells in the inflames tissue secrete cytokines called colony<stimulating factors, which promote production of more leukocytes (leukopoiesis) #y the red #one marrow. i. Eithin a few hours, the neutrophil count can raise from ',2221%,222 cellsDN( to as high as !%,222 cellsDN(, a condition called neutrophilia. ii. -n the case of an allergy or parasitic infection, and elevated eosinophil count, or eosinophilia, may also occur. 12. Tissue cleanup and repair is largely undertaken #y monocytes. a. =onocytes arrive within 8 to 1! hours of an in7ury, emigrate from the #loodstream, and turn into macrophages. i. =acrophages engulf and destroy #acteria, damaged host cells, and dead and dying neutrophils. ii. They also act as antigen<presenting cells (A6/s), activating specific immune responses. #. ,dema also contri#utes to tissue cleanup.

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i. 4welling compresses veins and reduces venous drainage, #ut forces open the valves of lymphatic capillaries and promotes lymphatic drainage. ii. (ymphatics collect and remove #acteria, dead cells, and other tissue de#ris #etter than do #lood capillaries. c. 3eutrophils and most macrophages die, and these dead cells and other tissue de#ris and fluid form a yellowish fluid called pus, which accumulates in a tissue cavity called an a#scess. i. 6us is usually a#sor#ed, #ut sometimes it forms a #lister #etween the epidermis and dermis and may #e released #y its rupture. d. "lood platelets and endothelial cells in an area of in7ury secrete platelet< derived growth factor, which stimulates fi#ro#lasts to multiply and synthesi:e collagen. e. Cyperemia delivers o$ygen and nutrients to the area, while the heat of the inflamed tissue increases meta#olic rate and mitosis speed. f. The fi#rin clot may provide a scaffold for tissue reconstruction. g. 6ain contri#utes to recovery in that it limits the use of a #ody part, giving it a chance to rest and heal.

III. )eneral *spects $% Speci%ic Immunity (pp. 8'( 8+1" A. The third line of defense, the immune system, is composed of a large population of widely distri#uted cells that recogni:e foreign su#stances and act to neutrali:e or destroy them. (p. 8.>) ". Two characteristics distinguish immunity from nonspecific resistance. (p. 8.8) 1. 4pecificity. -mmunity is directed against a particular pathogen. !. =emory. Ehen ree$posed to the same pathogen, the #ody reacts so 9uickly that no noticea#le illness occurs. /. Two forms of immunity are recogni:ed, called cellular immunity and humoral immunity+ these two forms interact, and they often respond to the same pathogen. (p. 8.8) 1. /ellular (cell<mediated) immunity employs lymphocytes that directly attack and destroy foreign or diseased cells. a. /ellular immunity is a way of fighting pathogens that reside inside human cells, such as viruses, some #acteria and yeasts, and proto:oans. #. -t also fights parasitic worms, cancer cells, and cells of transplanted tissues and organs. !. Cumoral (anti#ody<mediated) immunity involves anti#odies that do not directly destroy a pathogen, #ut tag them for destruction. a. The anti#odies, not the immune cells that produce them, attack the pathogen. #. FCumoralG comes from the old term for #ody fluids, Fhumors.G

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c. Cumoral immunity is effective against e$tracellular viruses, #acterial, yeasts, and proto:oans, as well as to$ins, venoms, and allergens. d. Cumoral immunity can work only against the e$tracellular stages of infectious organisms+ when these invade host cells, however, they may still #e vulnera#le to attack #y cellular immunity.

.. /ellular and humoral immunity are summari:ed and compared in Ta#le !1.%. '. -mmunity can also #e classified as active versus passive and natural versus artificial+ thus four classes of immunity can #e recogni:ed. a. -n natural active immunity, one produces oneIs own anti#odies andDor T cells as a result of natural e$posure to an antigen. #. -n artificial active immunity, one produces oneIs own anti#odies or T cells as a result of vaccination against a disease. i. A vaccine consists of dead or attenuated pathogens that can stimulate an immune response #ut normally cause little or no disease. ii. -n some cases periodic #ooster shots are given to restimulate immune memory. iii. A num#er of diseases, including smallpo$, have #een eliminated through vaccination. c. -n natural passive immunity, one ac9uires anti#odies produced #y another person, which confer temporary immunity. i. This normally occurs when a fetus ac9uires anti#odies from the mother #efore #irth, or an infant ac9uires them from her during #reast feeding. d. -n artificial passive immunity, temporary immunity results from in7ection of an immune serum from another person or animal that has produced anti#odies. i. -mmune serum is used for emergency treatment of snake#ite, #otulism, tetanus, ra#ies, and other diseases. %. 5nly the two forms of active immunity involve immune memory+ passive immunity typically lasts for only ! or . weeks. Cere we discuss the process of natural active immunity. 0. An antigen (Ag) is any molecule that triggers an immune response. (p. 8.A) 1. 4ome are free molecules such as venoms and to$ins+ others are components of plasma mem#ranes and #acterial cells. !. 4mall, universal molecules are not antigenic+ most antigens have molecular weights over 12,222 amu and are comple$ molecules. .. The immune system FlearnsG to distinguish self from nonself prior to #irth, and thereafter normally attacks only nonself antigens.

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'. 5nly regions of an antigen molecule called epitopes (antigenic determinants) stimulate immune responses+ one molecule typically has several different epitopes. %. Captens are molecules too small to #e antigenic, #ut that can stimulate an immune response #y #inding to a host molecule to create a uni9ue comple$. a. Captens cause allergic responses to cosmetics, detergents, industrial chemicals, poison ivy, and animal dander. #. The most common drug allergy is to penicillin and its derivatives+ penicillin is a hapten, and allergic reaction to it can cause death from anaphylactic shock. ,. (ymphocytes are one of the ma7or cells of the immune system, the others #eing macrophages and dendritic cells. (pp. 8.A18'2) 1. (ymphocytes fall into three classes8 natural killer (3;) cells descri#ed earlier, T lymphocytes, and " lymphocytes. !. T lymphocytes (T cells) have a three<stage life history of F#irth, training, and deployment,G and three anatomical stations where these stages occur. a. T cells are F#ornG in the red #one marrow as descendants of pluripotent stem cells (664/s). i. They are released into the #lood as still<undifferentiated stem cells that coloni:e the thymus. ( ig. !1.!2) #. The thymus is where the cells mature into fully functional T cells, their FtrainingG phase. i. -n the thymic corte$, reticular epithelial (?,) cells secrete thymic hormones that stimulate T cells to produce surface antigen receptors. ii. Eith receptors, T cells are immunocompetent, capa#le of recogni:ing antigens presented to them #y A6/s. iii. The ?, cells test the T cells #y presenting self<antigens to themD iv. ailure to recogni:e =C/ antigens on the ?, cells means elimination, as does reacting to self<antigens. v. T cells that fail are eliminated #y negative selection, either #y clonal deletion in which they die and are phagocyti:ed, or #y anergy in which they remain alive #ut unresponsive. vi. 3egative selection leaves the #ody in a state of self<tolerance. c. T cells that pass the test FgraduateGBonly !& of T cells passBand move to the medulla of the thymus. i. -n the medulla they undergo positive selection in which they form clones of identical T cells programmed to respond to a particular antigen.

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ii. These cells, which are immunocompetent #ut have not yet

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encountered the foreign antigens, constitute the naOve lymphocyte pool. d. The naOve T cells leave the thymus and coloni:e lymphatic tissues and organs throughout the #ody. .. " lymphocytes (" cells) differentiate from another group of fetal stem cells in the #one marrow. a. Those that respond to self<antigens undergo either anergy or clonal deletion. #. 4elf<tolerant " cells go on to produce surface receptors for antigens, divide, and produce immunocompetent " cell clones. c. These cells disperse throughout the #ody to the same organs as T cells. . Antigen<presenting cells (A6/s) are critical to assisting T cells to recogni:e foreign antigens. (pp. 8'218'1) 1. 0endritic cells, macrophages, reticular cells, and " cells function as A6/s. !. A6/ function depends on a family of genes on chromosome 6 called the ma7or histocompati#ility comple$ (=C/), which code for =C/ proteins. a. The =C/ proteins on the A6/ surface are shaped a #it like hotdog #uns with a groove for holding the foreign antigen. #. =C/ proteins are structurally uni9ue to every person e$cept for identical twins. .. Ehen an A6/ encounters an antigen, it performs antigen processing8 it internali:es the antigen #y endocytosis, digests it into fragments, and displays its epitopes in the grooves of the =/C proteins. ( ig. !1.!1a) '. Eandering T cells regularly inspect A6/s for displayed antigens. ( ig. !1.!1#) a. -f an A6/ presents a self<antigen, the T cells disregard it. #. -f it displays a nonself<antigen, the T cells initiate an immune attack. %. The many cell types involved in immunity re9uire chemical messengers to coordinate activities+ lymphocytes and A6/s communicate via the cytokines called interleukins. 6. Agents of specific immunity and their actions are summari:ed in Ta#le !1.'. I,. Cellular Immunity (pp. 8+1 8++" A. /ellular (cell<mediated) immunity is a form of specific defense in which T lymphcytes directly attack and destroy diseased or foreign cells+ the immune system then remem#ers the antigens of the invaders. (p. 8'1) ". /ellular immunity employs four classes of T cells. (pp. 8'118'!) 1. /ytoto$ic T (T/) cells are the FeffectorsG of cellular immunity that carry out attack+ they are also called killer T cells, #ut are not the same as 3; cells. !. Celper T (TC) cells promote the action of T/ cells as well as playing key roles in other forms of immunity+ all other T cells are involved only in cellular immunity.

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.. ?egulatory T (T?) cells, or T<regs, inhi#it multiplication and cytokine secretion #y other T cells and limit immune responses+ they may play a role in preventing autoimmune diseases. '. =emory T (T=) /ells are descended from cytoto$ic T cells and are responsi#le for memory. %. T? and T= are not widely used a##reviations, #ut T/ and TC are. 6. T/ cells are also known as T8, /08, or /08K cells #ecause they have a surface glycoprotein called /08. >. TC and T? cells are also known as T', /0', or /0'K cells #ecause they carry /0'. 8. /0 stands for cluster of differentiation. A. The /0 glycoproteins are cell<adhesion molecules. 12. The three stages of #oth cellular and humoral immunity are recognition, attack, and memory (three ?s8 recogni:e, react, and remem#er). /. The recognition phase has two aspects8 antigen presentation and T cell activation. (p. 8'!) 1. Ehen an antigen<presenting cell (A6/) encounters and processes an antigen, it migrates to the nearest lymph node and displays it to T cells. a. Ehen T/ and TC cells encounter a displayed antigen on an =C/ protein (=C/6) they initiate an immune response. #. T cells respond to two classes of =C/6s. i. =C/<- proteins occur on every nucleated cell and display small peptides from the cytoplasm+ if they are normal self<antigens, no T cell response occurs, #ut if they are viral proteins or a#normal cancer<cell antigens, they do elicit a response. ii. =C/<-- proteins (human leukocyte antigens, C(As) occur only on A6/s and display only foreign antigens. c. T/ cells respond only to =C/<- proteins, and TC cells respond only to =C/< --. (Ta#le !1.!) !. T cell activation occurs in several steps. (p. 8'!) ( ig. !1.!!) a. -t #egins when a T/ or TC #inds to an =C/6 displaying an epitope that the T cell is programmed to recogni:e. #. The T cell must then #ind to another A6/ protein, related to interleukins. c. This process, called costimulation, helps ensure that the immune system does not launch an attack in the a#sence of an enemy. d. 4uccessful costimulation triggers clonal selection, in which the activated T cell divides to give rise to a clone of programmed T cells. 0. 0uring the attack phase, TC and T/ cells play different roles. (pp. 8'!18'.) 1. Celper T cells are necessary for most immune responses.

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a. They play a coordinating role in #oth humoral and cellular immunity. ( ig. !1.!.) #. Ehen a TC cell recogni:es an Ag1=C/6 comple$, it secretes interleukins that have three effects. i. They attract neutrophils and 3; cells. ii. They attract and stimulate macrophages, and inhi#it them from leaving. iii. They stimulate T and " cell mitosis and maturation.

!. /ytoto$ic T cells are the only T lymphocytes that directly attack and kill other cells. ( ig. !1.!') a. Ehen a T/ cell recogni:es a comple$ of antigen and =C/<- protein on a diseased or foreign cell, it docks on it. #. -t then delivers a lethal hit of cytoto$ic chemicals. c. The T/ cell then goes off in search of other enemy cells d. The lethal hit includes three types of chemical agents. i. 6erforin and gran:ymes, which kill in the same manner as for 3; cells. ii. -nterferons, which inhi#it viral replication and recruit and activate macrophages. iii. Tumor necrosis factor (T3 ), which aids in macrophage activation and kills cancer cells. e. As more cells are recruited #y helper T cells, the immune response e$erts an overwhelming force again the pathogen, which peaks in a#out a week and then gradually declines. ,. -mmune memory follows the primary response. (pp. 8'.18'') 1. After clonal selection, some T/ and TC cells #ecome memory cells, which are long< lived and much more numerous than naOve T cells. !. =emory cells re9uire fewer steps for them to #ecome activated. .. Hpon ree$posure to the same pathogen later in life, memory cells mount a 9uick attack called the T cell recall response. a. 5ften this response destroys a pathogen so 9uickly that no noticea#le illness occurs. ,. -um$ral Immunity (pp. 8++ 85." A. -n humoral immunity, " lymphocytes produce anti#odies that #ind to antigens and tag them for destruction #y other means+ the same three stages of response occur.. (p. 8'') ". -n the recognition phase, an antigen #inds to several of the thousands of surface receptors on an immunocompetent " cell.

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1. The antigen links these receptors together and is then taken into the cell #y receptor< mediated endocytosis. !. After endocytosis, the " cell processes the antigen, links some epitopes to its =C/<-proteins, and displays these. .. =ost " cells re9uire #inding #y a helper T cell to this Ag1=C/6 comple$ for activation, although some are directly activated. a. Ehen a TC cell #inds, it secretes interleukins that activate the " cell. #. /lonal selection is triggered, giving rise to a #attalion of identical " cells programmed against the antigen. ( ig. !1.!%) '. =ost cells of the clone differentiate into plasma cells, which are larger than " cells and contain an a#undance of rough ,?. ( ig. !1.!6) a. 6lasma cells develop mainly in the terminal centers of the lymphatic nodules of the lymph nodes. #. A#out 12& of them remain in the nodes, #ut the rest take up residence in the #one marrow and elsewhere, where they produce anti#odies until they die after ' or % days. c. 0uring this time a plasma cell secretes anti#odies at the rate of !,222 molecules per second, which circulate throughout the #ody. d. The first time a person is e$posed to an antigen, the plasma cells produce -g=+ upon later e$posures they produce -g@. /. -n the attack phase, highly specific anti#odies are produced (pp. 8'618'8) 1. An anti#ody, also called an immunoglo#ulin (-g), is a defensive gamma glo#ulin found in #lood plasma, tissue fluids, #ody secretions, and some leukocyte mem#ranes. !. The #asic structural unit of an anti#ody, an anti#ody monomer, is composed of four polypeptides linked #y disulfide (14141) #onds. ( ig. !1.!>) a. The two larger heavy chains are a#out '22 amino acids long. #. The two light chains are a#out half that long. c. ,ach heavy chain has a hinge regions where the anti#ody is #ent, giving the monomer a T or P shape. .. All four chains have a varia#le (M) region that gives an anti#ody its uni9ueness. a. The M regions of a heavy chain and a light chain com#ine to form an antigen< #inding site on each arm. #. This site attaches to the epitope of an antigen molecule. '. The rest of each chain is a constant (/) region, which has the same amino acid se9uence as all anti#odies of a given class within an individual. a. The / region determines the mechanism of an anti#odyIs action.

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%. The five classes of anti#odies are -gA, -g0, -g,, -g@, and -g=, named for the structures of their / regions. (Ta#le !1..) a. -g0, -g,, and -g@ are monomers. #. -gA has a monomeric and a dimeric form. c. -g= is a pentamerBcomposed of five monomers.

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6. -g0 and -g= are surface antigen receptors synthesi:ed #y a developing " cell. >. -g@ is important in the immunity of the new#orn. a. -t crosses the placenta and transfers immunity from the mother to the fetus. 8. A new#orn also ac9uires some material -gA through #reast milk and colostrum. A. The human immune system is #elieved capa#le of producing at least 12 #illion and perhaps 1 trillion different anti#odies. a. Any one individual does not have the entire set of possi#ilities, #ut still an enormous potential for dealing with diverse antigens. #. A different gene does not e$ist for every anti#ody+ somatic recom#ination allows shuffling and com#ination of genes in nonreproductive (somatic) cells. c. " cells in the germinal centers of lymphatic nodules also undergo somatic hypermutation, #y which a large num#er of mutations create entirely new se9uences. 12. 5nce released #y a plasma cell, anti#odies use four mechanisms to render antigens harmless+ note that anti#odies do not directly destroy an antigen. a. 3eutrali:ation. 5nly certain regions of an antigen are pathogenic, and an anti#ody can neutrali:e an antigen #y masking these active regions. #. /omplement fi$ation. Ehen anti#odies -g= and -g@ #ind to enemy cells, they change shape and e$pose their complement<#inding sites. ( ig. !1.!>a) i. "inding of complement leads to inflammation, phagocytosis, immune clearance, and cytolysis. ( ig. !1.1%) ii. /omplement fi$ation is the primary mechanism of defense against foreign cells such as #acteria and mismatched erythrocytes. c. Agglutination occurs when an anti#ody molecule, with ! to 12 #inding sites, #inds to antigens on two or more enemy cells, sticking them together and preventing their spread. ( ig. !1.!8) d. 6recipitation is similar to agglutination, #ut it links antigen molecules and not whole cells, creating Ag1A# comple$es that are removed #y immune clearance or phagocyti:ed #y eosinophils. 0. The memory phase occurs as part of the primary response to first e$posure to an antigen. (pp. 8'818%2)

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1. -n the primary response, appearance of anti#odies is delayed . to 6 days while naOve " cells multiply and differentiate. !. As plasma cell #egin secreting anti#ody, the anti#ody titer rises. ( ig. !1.!A) a. -g= appears first, peaks in a#out 12 days, and soon declines. #. -g@ levels rise as -g= declines, #ut even -g@ titer drops within a month. .. 0uring clonal selection, some mem#ers of the clone #ecome memory " cells rather than plasma cells. ( ig. !1.!%) a. These cells, found mainly in germinal centers of lymph nodes, mount a very 9uick secondary (anamnestic) response if ree$posed to the same antigen. i. 6lasma cells form within hours, so the -g@ titer rises sharply+ the antigen may have no chance to create illness. ii. A low level of -g= is also secreted and 9uickly declines. #. -g@ remains elevated for weeks to years, #ut does not last as long as humoral immunity. '. Ta#le !1.' summari:es cellular and chemical agents involved in humoral and cellular immunity. %. Ta#le !1.% compares the main features of the two types of immunity. ,I. Immune System /is$rders (p. 85. 856" A. Cypersensitivity is an e$cessive, harmful immune reaction to antigens that most people tolerate. (p. 8%218%!) 1. -t includes reactions to transplanted tissues (alloimmunity), a#normal reactions to oneIs own tissues (autoimmunity), and allergies, which are reactions to environmental antigens called allergens ( ig. !!.A) a. Allergens occur in mold, dust, pollen, vaccines, insect venoms, animal dander, poison ivy to$ins, etc. as well as in food such as nuts, milk, eggs, and shellfish. #. 0rugs such as penicillin, tetracycline, and insulin are allergenic to some people. !. 5ne classification system recogni:es four kinds of hypersensitivity distinguished on the #asis of immune agents and their attack. a. Type -, or acute (immediate) hypersensitivity, includes the most common allergies. i. 4ome use the word allergy for type - reactions only, others for all four types. ii. Type - is an -g,<mediated reaction that #egins within second of e$posure+ it usually su#sides usually within .2 minutes, although it can #e severe and even fatal.

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iii. Allergens #ind to -g, on the mem#ranes of #asophils and mast cells, stimulating them to secrete histamine and other inflammatory and vasoactive chemicals. iv. /linical signs include local edema, mucus hypersecretion and congestion, watery eyes, runny nose, hives, and sometimes cramps, diarrhea, and vomiting. v. 4ome e$amples of type - hypersensitivity are food allergies and asthma, a local reaction to inhaled allergens.

Insight 21.3 Asthma #. Anaphyla$is is an immediate and severe type - reaction. i. (ocal anaphyla$is can #e relieved with antihistamines. ii. Anaphylactic shock is a severe, widespread, acute hypersensitivity that occurs when an allergen is introduced into the #loodstream. iii. -t is characteri:ed #y #ronchoconstriction, dyspnea, vasodilation, circulatory shock, and sometimes sudden death. iv. Antihistamines are inade9uate #y themselves, #ut epinephrine can relieve the symptoms+ fluid therapy and respiratory support are sometimes re9uired. c. Type -- (anti#ody<dependent cytoto$ic) hypersensitivity occurs when -g@ or -g= attacks antigens #ound to cell surfaces. i. The reaction leads to complement activation and lysis or opsoni:ation of the target cell. ii. ,$amples of cell destruction #y type -- reactions are #lood transfusion reaction, pemphigus vulgaris, and some drug reactions. iii. -n some other type -- responses, an anti#ody #inds to cell surface receptors and either interferes with function (myasthenia gravis) or overstimulates function (to$ic goiter). d. Type --- (immune comple$) hypersensitivity occurs when -g@ or -g= forms Ag1A# comple$es that precipitate #eneath the endothelium of #lood vessels or in other tissues. i. At the sites of deposition, these comple$es activate complement and trigger inflammation, causing tissue destruction. ii. Two e$ample of type --- hypersensitivity are acute glomerluonephritis and systemic lupus erythematosus. (Ta#le !1.6) e. Type -M (delayed) hypersensitivity is a cell<mediated reaction in which signs appear 1! to >! hours after e$posure.

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i. A6/s in the lymph nodes display antigens to helper T cells, and these secrete interferon and other cytokines to activate cytoto$ic T cells and macrophages. ii. The result is a mi$ture of nonspecific and immune responses. iii. Type -M reaction include allergies to haptens in cosmetics and poison ivy, graft re7ection, the tu#erculosis skin test, and #eta cell destruction that causes type 1 dia#etes mellitus.

". Autoimmune diseases are failure of self<tolerance in which the immune system produces autoanti#odies. (p. 8%!) 1. 4elf<tolerance may fail for at least three reasons. a. /ross<reactivity. 4ome anti#odies against foreign antigens react to similar self<antigens, such as in rheumatic fever. i. A streptococcus infection stimulates production of anti#odies that also react against heart tissue. ii. 4carring and stenosis (narrowing) of mitral and aortic valves can result. #. A#normal e$posure of self<antigens to the #lood. 4ome native antigens are not normally e$posed, and when they are, a response may occur. i. The #lood1testis #arrier ("T") normally isolates sperm cells form the #lood. ii. "reakdown of this #arrier can cause sterility when sperm first form and active the production of autoanti#odies. c. /hanges in the structure of self<antigens. Miruses and drugs may change the structure of self<antigens so that they appear foreign. i. 5ne theory of type 1 dia#etes mellitus is that a viral infection alters antigens of the #eta cells. ii. An autoimmune attack is then mounted against these cells. !. ,vidence indicates that not all self<reactive T cells are eliminated #y clonal detection in the thymus. a. ?egulatory T cells, whose e$istence was confirmed only in 1AA%, keep these in check and normally prevent autoimmune diseases. /. -mmunodeficiency diseases are those in which the immune system fails to respond vigorously enough. (pp. 8%!18%%) 1. 4evere com#ined immunodeficiency disease (4/-0) is a group of disorders caused #y recessive alleles that result in scarcity or a#sence of #oth T and " cells. a. /hildren with 4/-0 are highly vulnera#le to opportunistic infections and must live in protective enclosures. ( ig. !1..2)

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#. These children are sometimes helped #y transplants of #one marrow or fetal thymus, #ut in some cases the transplanted cells fail to survive, or they attack the recipientIs tissues (graft<versus<host response).

!. Ac9uired immunodeficiency diseases are nonhereditary diseases contracted after #irth. a. The #est<known e$ample is ac9uired immunodeficiency syndrome (A-04), a group of conditions that involved a severely depressed immune response. #. A-04 is caused #y infection with the human immunodeficiency virus (C-M). c. 4tructurally, the inner core of C-M consists of a protein capsid enclosing two ?3A molecules, two reverse transcriptase molecules, and a few other en:ymes. ( ig. !1..1a) d. The capsid is enclosed in another layer of viral protein, the matri$. e. ,$ternal to this is a viral envelope of phospholipids and glycoproteins derived from the host cell. f. C-M can replicate only inside a living host cell+ it invades helper T (/0') cells, dendritic cells, and macrophages. i. -t adheres to a target cell #y means of an envelope glycoprotein and tricks the cell into internali:ing it #y receptor<mediated endocytosis. ii. Eithin the host cell, reverse transcriptase uses the viral ?3A as a template to synthesi:e 03A (viruses capa#le of this are termed retroviruses). iii. The new 03A is inserted into the host cellIs 03A, where it may lie dormant for months to years. iv. Ehen activated, it induces the host cell to replicate the virus components+ as they emerge, they are coated with #its of the cellIs plasma mem#rane. ( ig. !1..1#) g. "y destroying helper T cells, C-M strikes the coordinating agent of nonspecific defense, humoral immunity, and cellular immunity. ( ig. !1.!.) h. After the incu#ation period ends, the patient #egins to e$perience flulike episodes of chills and fever as C-M attacks the TC cells. i. At first, anti#odies against C-M are produced and the TC count returns nearly to normal. ii. As the virus destroys more and more cells, however, the symptoms #ecome more pronounced and include night sweats, fatigue, headache, e$treme weight loss, and lympadenitis. i. A normal TC count is 622 to 1,!22 cellsDN(, #ut a criterion of A-04 is a count less than !22DN(.

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6age !A
7. Eith such a severe depletion of TC cells, a person succum#s to opportunistic infections with such pathogens as Toxoplasma, Pneumocystis, herpes simple$ virus, cytomegalovirus, or tu#erculosis #acteria. i. Ehite patches (leukoplakia) may appear in the mouth cause #y Candida (thrush) or ,pstein<"arr virus. ii. A cancer, ;aposi sarcoma, is common in A-04 patients, and affects endothelial cells of the #lood vessels. ( ig. !1..!) k. 0eath from cancer or infection is inevita#le, usually within a few months #ut sometimes as long as 8 years. l. 4ome C-M<positive people have survived for 12 years or longer without developing A-04. m. C-M is transmitted through #lood, semen, vaginal secretions, and #reast milk, and can also #e transmitted from mother to fetus through the placenta. i. C-M occurs in saliva and tears, #ut is apparently not transmitted #y those fluids. ii. The most common means of transmission are unprotected se$ual intercourse, contaminated #lood products, and in7ections with contaminated needles. iii. Eorldwide, a#out >%& of C-M infections are ac9uired through heterose$ual, vaginal intercourse. iv. -n the H.4., most cases occur in men who have se$ with other men, #ut adolescents are the fastest rising group #ecause of the e$change of unprotected se$ual intercourse for drugs. v. 4haring of needles for drug use remains the chief means of transmission in ur#an ghettos. vi. 4ince 1A8', all #lood donated for transfusion has #een tested for C-M, and the risk of infection from this means is less than 1&. vii. A-04 is not known to #e transmitted through casual contact, or #y kissing, or from mos9uitoes or other #lood sucking arthropods. n. C-M survives poorly outside the human #ody and is destroyed #y laundering, dishwashing, e$posure to heat of %2L/ (1.%L ) for 12 minutes, chlorination of swimming pools, and disinfectants such as #leach, (ysol, hydrogen pero$ide, ru##ing alcohol, and germicidal skin cleansers. o. A properly used, undamaged late$ condom is an effective #arrier to C-M, #ut not animal mem#rane condoms. p. =any efforts have #een launched to find a vaccine or cure for A-04. 9. A#out 1& of C-MIs genes mutate every year.

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6age .2
i. This mutation rate is a #arrier to #oth natural immunity and vaccine development. ii. The virus soon evolves new surface antigens that escape recognition #y any immune cells that have #ecome sensiti:ed to it. iii. The high mutation rate means that a vaccine that works today may #e ineffective against future strains. r. The first anti<C-M drugs include a:idothymidine (AQT, ?etrovir), which inhi#its reverse transcriptase, and protease inhi#itors+ C-M has developed resistance to these drugs. s. Today at least !' anti<C-M drugs are on the market, #ut none totally eliminates the virus and all have serious side effects. t. A num#er of unanswered 9uestions e$ist a#out C-M, such as its patterns of transmission in different countries, and why some people succum# 9uickly while others do not develop the disease.

.. Ta#le !1.6 descri#es additional lymphatic and immune system disorders. Insight 21.4 3euroimmunologyBThe =ind<"ody /onnection C$nnecti0e Issues1 Lymphatic and Immune System Interacti$ns

/ross ?eference
Additional information on topics mentioned in /hapter !1 can #e found in the chapters listed #elow. /hapter >8 The two types of #one marrow, red and yellow. /hapter 1>8 ,icosanoid synthesis /hapter 188 The types of leukocytes /hapter 188 6luripotent stem cells