1. The Lymphatic System Chapter 20

2. Introduction The lymphatic system supports the function of the cardiovascular and immune systems of the body The lymphatic system consists of two semi-independent parts –A network of lymphatic vessels –Lymphoid organs scattered throughout the body

3. Introduction The lymphatic vessels transport fluids that have escaped from the cardio- vascular system The main components of the immune system (lymphocytes, lymphoid tissue, and lymphoid organs) fight infections and confer immunity to disease

4. The Lymphatic System An elaborate system of lymphatic vessels runs throughout the body These vessels collect a fluid called lymph from the loose connective tissue around blood capillaries and carry this fluid to the great veins at the root of the neck

5. The Lymphatic System Because lymph flows only toward the heart, the lymphatic vessels form a one-way system rather than a full circuit

6. The Lymphatic System There are several orders of vessels –Lymph capillaries –Lymphatic collecting vessels –Lymph nodes –Lymph trunks –Lymph ducts

7. The Lymphatic System Recall that all blood capillaries are surrounded by a loose connective tissue that contains tissue fluid or interstitial fluid The fluid arises from blood filtered through the capillary walls

8. The Lymphatic System Tissue fluid consists of small molecules of blood plasma, water, various ions, nutrient molecules, and respiratory gases

9. The Lymphatic System Tissue fluid is continuously leaving and re-entering the blood capillaries For complex reasons slightly more fluid arises from the arteriole end than re- enters the venule end This amounts to about 3 liters a day

10. The Lymphatic System The lymphatic vessels function to collect this excess fluid and return it to the bloodstream Any blockage of the lymphatic vessels causes the affected body region to swell with excess tissue fluid resulting in edema

11. The Lymphatic System The lymphatic vessels also perform another related function Blood proteins leak slowly from blood capillaries into the surrounding tissue fluid Lymph vessels return leaked proteins to the bloodstream This is important because proteins in blood generate osmotic forces that are essential for keeping water in the bloodstream

12. Lymph Capillaries Lymph capillaries are permeable vessels that receive the tissue fluid They are located near blood vessels in the loose connective tissue Like blood capillaries their walls consists of a single layer of endothelial cells

13. Lymph Capillaries Lymph capillaries are very permeable The permeability results from the structure and arrangement of the endothelial cells They have few intercellular junctions

14. Lymph Capillaries In lymph capillaries the adjacent edges of cells overlap to form easily opened mini- valves These valves open to allow tissue fluid to enter the lymphatic capillary Collagen filaments anchor the cells to the connective tissue

15. Lymph Capillaries The minivalves work because the collagen filaments anchor portions of the cell wall to the surrounding connective tissue Any fluid pressure in the volume of the tissue fluid separates the minivalves This opens gaps in the wall of the capillary allowing fluid to enter Once in the lymphatic capillary, it cannot leak out, because backflow pressure forces the minivalve flaps together

16. Distribution of Lymphatic Vessels Lymph capillaries are widespread, occurring almost everywhere blood capillaries occur Lymph capillaries are absent from bone and teeth, bone marrow, and the entire central nervous system

17. Lymph Capillaries Once interstitial fluid enters the lymphatic ducts it is called lymph Although the high permeability of lymph capillaries allows the uptake of large quantities of tissue fluid and protein molecules it also allows bacteria, viruses, or cancer cells in the loose connective tissue to enter these capillaries with ease

18. Lymph Capillaries These pathogenic agents can then travel throughout the body via the lymphatic vessels However, most pathogenic agents are destroyed in the lymph nodes by various antibodies before reaching the general circulation Cancer cells can be the most problematic and can actually use lymph nodes as a site to metastasize further

19. Lymph Capillaries Lymph capillaries are widespread, occurring almost everywhere blood capillaries occur

20. Lymph Capillaries Lymph capillaries are absent from bone and teeth, from bone marrow, and from the entire CNS In the CNS excess fluid drains into the cerebrospinal fluid and then returns it to the blood at the superior sagittal sinus

21. Lymph Collecting Vessels From the lymph capillaries, lymph enters lymphatic collecting vessels which accompany blood vessels

22. Lymph Collecting Vessels In general, the superficial lymphatic collecting vessels in the skin travel with superficial veins Deep lymphatic collecting vessels of the trunk and digestive viscera travel with the deep arteries

23. Lymph Collecting Vessels Lymphatic collecting vessels are narrow and delicate and are usually not seen in a laboratory dissection The vessels have the same tunics as blood vessels but their walls are always thinner The thinness reflects the fact that lymph flows under very low pressure and have no pump to move the lymph along

24. Lymph Collecting Vessels To direct the flow of lymph, lymphatic collecting vessels contain more valves than do veins At the base of each valve, the vessel bulges, forming a pocket in which lymph collects and forces the valve shut

25. Lymph Collecting Vessels Because of these bulges, each collecting vessel resembles a string of beads This distinctive appearance, which characterizes the larger lymph ducts as well allow MD’s to recognize lymph vessels in X-rays

26. Lymph Collecting Vessels Unaided by pressure from a pump, lymph is propelled through lymph vessels by a series of weaker mechanisms The action of contracting skeletal muscle and the pulsation of nearby arteries push on lymph vessel, squeezing lymph through them

27. Lymph Collecting Vessels The muscular tunica media of the lymph vessels also contacts to help propel the lymph Additionally, the normal movements of the limbs and trunk keep the lymph flowing Despite these mechanisms, the transport of lymph is slow People who are inactive or who stand for long times often develop edema

28. Lymph Nodes Lymph nodes, which cleanse the lymph of pathogens are bean shaped organs situated along lymphatic collecting vessels The term lymph gland is not correct because they are not glandular in their function There are about 500 lymph gland in the body

29. Lymph Nodes Large clusters of superficial lymph nodes in the cervical, axillary, and inguinal regions The superficial cervical nodes along the jugular and carotid arteries receive lymph from the head and neck

30. Lymph Nodes Axillary nodes in the armpit filter lymph from the upper limbs

31. Lymph Nodes The inguinal nodes in the superior thigh filter lymph from the lower limb

32. Lymph Nodes Nodes in the mediastinum such as the deep tracheobronchial nodes receive lymph from the thoracic viscera

33. Lymph Nodes Deep nodes along the abdominal aorta, called aortic nodes, filter lymph from the posterior abdominal wall

34. Lymph Nodes Finally, deep nodes along the iliac arteries, called iliac nodes, filter lymph from the pelvic organs and the lower limbs

35. Lymph Nodes The microscopic anatomy of a lymph node suggests its role as a body filter The node is surrounded by a fibrous capsule of dense connective tissue

36. Lymph Nodes Fibrous strands of connective tissue called trabecule extend inward to divide the node into compartments

37. Lymph Nodes Lymph enters the convex aspect of the node through several afferent lymphatic vessels and exits from the indented region on the other side, the hilus, through efferent lymphatic vessels

38. Lymph Nodes Between the afferent and efferent vessels, lymph percolates through lymph sinuses These large lymph capillaries are spanned internally by a crisscrossing network of reticular fibers

39. Lymph Nodes The reticular fibers are covered by star-shaped endothelial cells Many macrophages live on this fiber network, phagocytizing pathogens and foreign particles in the lymph that flows through the sinuses

40. Lymph Nodes Most lymph passes through several nodes It is usually free of pathogens by the time it leaves its last node and enters the lymph trunks on its way to the great veins in the neck

41. Lymph Nodes Along with its lymph sinuses, a lymph node also contains tadpole shaped masses of lymphoid tissue This tissue is divided into outer (cortex) and inner (medulla) regions and are part of the immune system

42. Lymph Trunks After leaving the lymph nodes, the largest lymphatic collecting vessels converge to form lymph trunks These trunks drain large areas of the body

43. Lumbar Trunks The paired lumbar trunks lie along either side of the aorta in the inferior abdomen They receive all lymph draining from the lower limbs, pelvic organs and some of the anterior abdominal wall

44. Intestinal Trunk The unpaired intestinal trunk lies near midline on the posterior abdominal wall It receives fatty lymph (chyme) from the stomach, intestines, and other digestive organs

45. Brachiomediastinal Trunks These paired trunks ascend near the sides of the trachea They collect lymph from the thoracic viscera and thoracic wall

46. Subclavian Trunks These are paired trunks located near the sides of the trachea These trunks receive lymph from the upper limbs They also drain the inferior neck and the superior thoracic wall

47. Jugular Trunks These trunks are located in the neck at the base of each internal jugular vein These trunks drain lymph from the head and neck

48. Lymph Ducts The lymph trunks drain into the largest vessels the lymph ducts The number of ducts in an individual may vary from two to only only duct

49. Thoracic Duct The thoracic duct is present in all individuals Its most inferior part, located at the union of the lumbar and intestinal trucks is the cisterna chyli which lies on the bodies of vertebrae L 1 + L 2

50. Thoracic Duct The thoracic duct ascends along the vertebral bodies In the superior thorax, it turns left and empties into the venous circulation at the junction of the internal jugular and left subclavian veins

51. Right lymphatic Duct Some people have a short right lymphatic duct formed by the union of the right jugular, subclavian, and broncho- mediastinal trunks

52. Right lymphatic Duct When present, this duct empties into the neck veins at or near the junction of the right internal jugular and subclavian veins The right lymphatic duct drains the upper quarter of the body

53. Right lymphatic Duct In individuals without a right lymphatic duct, the three trunks empty separately into the neck veins

54. Lymphatic Vessels In summary, the lymphatic vessels…. –Return excess tissue fluid to the bloodstream –Return leaked proteins to the blood –Carry absorbed fat from the intestine to the blood through lacteals

55. Immune System The immune system is central to the body’s fight against disease Unlike the body’s other defense systems, it recognizes and attacks specific foreign molecules It destroys pathogens more and more effectively with each new exposure

56. Immune System The immune system centers around the key defense cells from lymphocytes But it also includes lymphoid tissue, and the lymphoid organs these include… –Lymph nodes, spleen, thymus, tonsils, aggregated lymphoid nodules in the small intestine, and appendix

57. Lymphocytes Infectious microorganisms that penetrate the epithelial barriers of the body enter the underlying loose connective tissues, where they are attacked by the inflammatory response, by macrophages and finally, by lymphocytes of the immune system Lymphocytes are white blood cells and that each lymphocyte recognizes and attacks its own type of foreign molecule, called an antigen

58. Lymphocytes B lymphocytes multiply to become plasma cells that secrete antibodies Cytotoxic (CD8 + ) T lymphocytes destroy antigen bearing cells by penetrating their membranes and inducing programmed cell death

59. Lymphocytes B and T cells continuously travel in the blood and lymph streams to reach infected connective tissues throughout the body, where they fight infection They repeatedly enter and exit these connective tissues, including the often infected lymphoid tissue, by squeezing through the walls of capillaries and venules

60. Lymphocytes This repeated movement of activated lymphocytes between the circulatory vessels and the connective tissues, called recirculation, ensures that lymphocytes reach all infection sites quickly

61. Lymphocyte Activation Immature lymphocytes go through several stages before they are able to attack antigens Most lymphocytes pass through these stages during infancy and childhood, by many do so in adulthood as well

62. Lymphocyte Activation This illustration provides an overview of lymphocyte activation

63. Lymphocyte Activation Lymphocytes originate in the bone marrow from lymphoid stem cells, some of which travel in the bloodstream to the thymus in the thorax and become T lymphocytes (T is for Thymus)

64. Lymphocyte Activation Other lymphocytes stay in the bone marrow and become B lymphcytes

65. Lymphocyte Activation These new T and B lymphocytes divide rapidly and generate many lymphocyte families (clones), each of which is able to recognize one unique type of antigen (this is called gaining immunocompetence)

66. Lymphocyte Activation Young T or B lymphocytes travel through the bloodstream to an infected connective tissue, where it binds to its specific antigen, an encounter called antigen challenge

67. Lymphocyte Activation As a consequence of the antigen challenge the lymphocyte becomes fully activated, gaining the ability to attack its antigen, proliferates rapidly, and produces mature lymphocytes that recirculate throughout the body seeking pathogens to attack

68. Lymphocyte Activation During the antigen challenge, an activating lymphocyte interacts with several other cells types The lymphocyte receives its antigen from an antigen presenting cell, such as a macrophage that has recently phagocytized the antigen, or a star shaped dendritic cell, a professional antigen gathered that patrols the body seeking antigens and carries them to places where lymphocytes gather

69. Lymphocyte Activation A distinct type of lymphocyte, called a helper (CD4 + ) T lymphocyte, secretes chemical signals that greatly stimulate the proliferation of activating B and cytotoxic T lymphocytes Helper T cells are important because their signals amplify and fine-tune the immune response

70. Lymphocyte Activation The importance of helper T lymphocytes is illustrated by acquired immune deficiency syndrome (AIDS), a viral disease in which a drastic decline in the body’s helper T cells greatly weakens the immune system

71. Lymphocyte Activation As more activating T or B cells proliferates within infected connective tissue, it produces two types of mature lymphocytes, effector and memory Short lived effector lymphocytes attack the pathogen immediately and then die Memory lymphocytes, by contrast, wait until the body encounters their antigen again - maybe decades later

72. Lymphocyte Activation When a memory lymphocyte finally encounters its antigen, its proliferating response and its attack are most vigorous and rapid Memory lymphocytes are the basis for acquired immunity They guard against subsequent infections and prevent us from getting many diseases more than once There are T and B varieties of memory lymphocytes

73. Lymph Nodes: Clinical Inflammation of a node is caused by a large number of bacteria trapped in a node –Inflammation results in swelling and pain Lymph nodes can become secondary cancer sites, particularly in metastasizing cancers that enter lymphatic vessels and become trapped –Cancer infiltrated nodes are swollen but not painful

74. Lymphoid Tissue Lymphoid tissue is an important component of the immune system because it –Houses and provides a proliferation site for lymphocytes –Furnishes an ideal surveillance vantage point for both lymphocytes and macrophages

75. Lymphoid Tissue Lymphoid tissue is the most important tissue of the immune system The tissue is an often infected connective tissue in which vast quantities of lymphocytes gather to fight invading microorganisms This tissue had two general locations –Mucous membranes –Lymphoid organs

76. Lymphoid Tissue Mucous membranes –Found within the digestive, respiratory, urinary and reproductive tracks where it is called mucosa-assocaited lymphoid tissue (MALT) Lymphoid Organs –Lymph nodes, spleen, thymus, tonsils, aggregated lymphoid nodules, and appendix

77. Lymphoid Tissue This tissue is the main battleground in the fight against infection Lymphoid tissue is where most lymphocytes become activated and most effector and memory lymphocytes are generated

78. Lymphoid Tissue Lymphoid tissue, a type of loose connective tissue called reticular connective tissue, dominates all lymphoid organs except the thymus The dark staining areas represent the connective tissue fibers

79. Lymphoid Tissue The structural features of lymphoid tissue serves its infection fighting role It is a reticular connective tissue whose basic framework is a network of reticular fibers secreted by reticular cells (fibroblasts)

80. Lymphoid Tissue Within the spaces of this network reside the many T and B lymphocytes that arrive continuously from venules coursing through the tissue Lymphocytes Macrophage Reticular fiber

81. Lymphoid Tissue Macrophages on the fiber network kill invading microorganisms by phagocytosis and along with dendritic cells, they activate nearby lymphocytes by presenting them with antigens Lymphocytes Macrophage Reticular fiber

82. Lymphoid Tissue Evident within lymphoid tissues are scattered, spherical clusters of densely packed lymphocytes, called lymphoid nodules or follicles These nodules often exhibit lighter staining germinal centers

83. Lymphoid Tissue Nodules derive from the activation of a single B cell, whose rapid proliferation generates the thousands of lymphocytes in the nodule Newly produced B cells migrate away from the nodule to become plasma cells

84. Lymphoid Organs Lymphoid organs are the lymph nodes, spleen, thymus, aggregated lymphoid nodules in the small intestine, and appendix

85. Lymphoid Organs Lymph nodes are more than filters The regions of the node between the lymph sinuses are tadpole shaped masses of lymphoid tissue

86. Lymphoid Organs As lymph moves through the sinuses, some of the contained antigens leak out through the sinus wall into the lymphatic tissue Most antigen challenges in the human body occur in the lymph nodes

87. Lymphoid Organs In the lymph nodes antigens are destroyed and B and T lymphocytes are activated The activation adds to the body’s supply of memory lymphocytes that offer long term immunity

88. Lymphoid Organs Lymph nodes have two histologically distinct regions, an external cortex and a medulla All the lymphoid nodules and most B cells occupy the lymphoid tissue of the most superficial part of the cortex

89. Lymphoid Organs Deeper in the cortex the lymphocytes are primarily T cells, especially helper T cells that increase the activity of B cells in the nearby nodules

90. Lymphoid Organs Thin, inward extensions from the cortical lymphoid tissue help define the medulla These cord like medullary extensions contain both T and B lymphocytes, plus plasma cells

91. Spleen The soft, blood rich spleen is the largest lymphoid organ Its size varies greatly among individual, but on average it is the size of a fist

92. Lymph Nodes Dendritic cells nearly encapsulate the follicles and abut the rest of the cortex, which primarily houses T cells in transit The T cells circulate continuously between the blood, lymph nodes, and lymphatic stream, performing their surveillance role

93. Spleen The large splenic vessels enter and exit the spleen on the anterior surface along a line called the hilus

94. Spleen The spleen has two main blood cleansing functions –The removal of blood-borne antigens (its immune function) –The removal and destruction of aged or defective blood cells Additionally, the spleen is a site of hematopoiesis in the fetus and stores blood platelets throughout life

95. Spleen The spleen is surrounded by a fibrous capsule from which trabeculae extend inward The larger branches of the splenic artery run in the trabeculae and send smaller arterial branches into the substance of the spleen

96. Spleen The arterial branches are called central arteries because they are enclosed by thick sleeves of lymphoid tissue that collectively constitute the white pulp of the spleen

97. Spleen Blood borne antigens enter this lymphoid tissue and are destroyed as they activate the immune response Surrounding the white pulp is red pulp which has two parts –Venous sinuses –Splenic cords

98. Spleen Venous sinuses are sinusoid capillaries that arise from the distal branches of the central arteries outside of the white pulp

99. Spleen Splenic cords consist of reticular connective tissue that is exceptionally rich in macrophages Whole blood leaks from the sinuses into this connective tissue where macrophages then phagocytize any defective blood cells

100. Spleen Red pulp is responsible for the spleen’s ability to dispose of worn-out blood cells White pulp provides the immune function of the spleen

101. Thymus The two lobed thymus lies in the anterior thorax and inferior neck, just posterior to the sternum

102. Thymus The thymus is the site at which immature lymphocytes develop into T lymphocytes The thymus secrets thymic hormones such as thymopoietin which causes T lymphocytes to gain immunocompetence

103. Thymus Prominent in newborns, the thymus continues to increase in size during childhood when it is most active During late adolescence, it begins to atrophy gradually, as its functional tissue is slowly replaced with fibrous and fatty tissue

104. Thymus At age 20 it still has about 80% of its functional tissue but at age 40 it typically retains only 5% of its functional tissue By age only 2% of functional tissue remains and the thymus is a fatty mass that is difficult to distinguish from surrounding connective tissue However, even as it atrophies, the thymus continues to produce immunocompetent cells throughout adulthood (reduced rate)

105. Thymus Again, the thymus lies in the superior thorax

106. Thymus The thymus contains numerous lobules arranged like fronds in the head of a cauliflower Each lobule contains an outer cortex and an inner medulla

107. Thymus The cortex is packed with rapidly dividing T lymphocytes gaining immunocompetence The medulla contains fewer lymphocytes In addition, the medulla contain the thymic (Hassall’s) corpuscles which seem to be collections of degenerating epithelial reticular cells The number and size of these corpuscles increases with age

108. Thymus The thymus differs from other lymphoid organs in two basic ways (First) –It functions strictly in lymphocyte maturation and thus is the only lymphoid organ that does not directly fight antigens –The blood-thymus barrier, keeps blood- borne antigens from leaking out of thymic capillaries and prematurely activating the immature thymic lymphocytes

109. Thymus The thymus differs from other lymphoid organs in two basic ways (Second) –The tissue framework of the thymus is not a true lymphoid connective tissue –The thymus arises like a gland from the epithelium lining the embryonic pharynx –Its basic tissue framework consists of star shaped epithelial cells rather that reticular fibers

110. Thymus The thymus differs from other lymphoid organs in two basic ways (Second) –These epithelial reticular cells secrete the thymic hormones that stimulate T cells to become immunocompetent –The thymus has no lymphoid nodules because it lack B cells

111. The Tonsils The tonsils are perhaps the simplest lymphoid tissue They are mere swellings of the mucosal lining of the pharynx

112. The Tonsils There are four groups of tonsils, palatine, lingual, pharyngeal, and tubal

113. The Tonsils The palatine tonsils lie directly posterior to the mouth and palate on the lateral sides of the pharyngeal wall These are the largest tonsils and the ones most often infected and removed during childhood (tonsillectomy) The lingual tonsil lie on the posterior surface of the tongue

114. The Tonsils The pharyngeal tonsil (adenoids) lie on the pharyngeal roof The tubal tonsils are just behind the openings of the pharyngotympanic tubes into the pharynx

115. The Tonsils The four tonsils are arranged in a ring around the entrance to the pharynx to gather and remove many pathogens that enter the pharynx in inspired air and swallowed food The tonsils process the antigens, then set up immune responses

116. The Tonsils The tonsils consist of an epithelium underlain by a connective tissue lamina propria

117. The Tonsils In the tonsils the underlying propria consists of abundant mucosa associated lymphoid tissue (MALT) packed with lymphocytes and scattered lymphoid nodules Germinal centers

118. The Tonsils The overlying epithelium invaginates deep into the interior forming blind ended structures called crypts that trap bacteria and particulate matter

119. The Tonsils The trapped bacteria work their way through the epithelium into the underlying lymphoid tissue causing the activation of lymphocytes

120. The Tonsils The trapping of bacteria in the crypts leads to many infections during childhood But it also generates a great variety of memory lymphocytes for long-term immunity

121. The Tonsils By inviting an infection, the tissue produces a wide variety of immune cells with a “memory” for the trapped pathogens The early risk during childhood results in better health in adulthood

122. Aggregates of Lymphoid Follicles Many bacteria permanently inhabit the hollow interior of the intestines and are constantly infecting the intestinal walls To fight these invaders, MALT is especially abundant in the intestine In two parts of the intestine, MALT is so large, permanent, and densely packed with lymphocytes that is said to form lymphoid organs: Aggregated lymphoid nodules and the appendix

123. Aggregates of Lymphoid Follicles Aggregated lymphoid nodules (Peyer’s patches) are clusters in the walls of the distal part of the ileum of the small intestine About 40 of these patches are present averaging about 1 cm and 1 cm wide Peyer’s Patches

124. Aggregates of Lymphoid Follicles Aggregates of lymphoid follicles are ideally situated to destroy bacteria thereby preventing these pathogens from breaching the intestinal wall

125. The Appendix The appendix is a tubular offshoot of the first part of the (cecum) of the large intestine

126. The Appendix Lymphoid tissue is also heavily concentrated on the walls of the appendix Histological sections reveal that dense lymphoid tissue uniformly occupies over half the thickness of the wall of the appendix

127. The Appendix Beside destroying the microorganisms that invade them, the aggregated lymphoid nodules and the appendix sample many different antigens from within the digestive tube and generate a wide variety of memory lymphocytes to protect the body