1. Lymphatic tissue

2. Components of lymphoid system
Lymph and lymph nodes
Lymph – fluid scavenged from the intersitium
Collected in thin walled lymphatic vessels
Returned to general circulation
Contains leukocytes
Filtered through small specialized organs (lymph nodes)

3. Lymph Capillaries lose 2-4 L of fluid and plasma protein
Lymphatic system absorbs excess fluid and returns it to the bloodstream
Makes sure circulatory system has enough blood to work properly
Decreases edema

4. Lymph– Lymphatic vessels Clear colorless fluid—like plasma
Less proteins
Has bacteria, virus, cell debris
Lipid content high
Lymphocytes content high
Many in capillary bed
Lymphatic vessels
Take fluid from tissue back to the bloodstream—veins
Usually along side of vein
Similar to vein (low pressure, use SK muscle and respiratory pump to help flow, valves also)

7. Lymphoid Cells Both types originate from stem cells in bone marrow
The two main varieties are T cells and B cells
Both types originate from stem cells in bone marrow
T cells – cell mediated immunity
B cells – humoral/ antibody mediated immunity
Small and large lymphocytes in peripheral blood
Large are the activated B lymphocytes
Antigen – anything the body perceives as foreign
Bacteria and their toxins; viruses
Mismatched RBCs or cancer cells

8. Lymphocytes T cells Manage the immune response
Attack and destroy foreign cells
B cells
Produce plasma cells, which secrete antibodies
Plasma cells are derived from activated B lymphocytes that have left the blood stream and taken up residence in connective tissue. SPOKE wheel appearance
Antibodies immobilize antigens

9. Other Lymphoid Cells
Macrophages – phagocytize foreign substances and help activate T cells
Dendritic cells – spiny-looking cells with functions similar to macrophages
Reticular cells – fibroblast like cells that produce a stroma, or network, that supports other cell types in lymphoid organs

10. Lymphoid Tissue Lymphatic follicles (nodules)
Solid, spherical bodies consisting of tightly packed reticular elements and cells
Have a germinal center composed of dendritic and B cells
Found in isolation and as part of larger lymphoid organs

13. Introduction
Lymphoid system consists of cells, tissues & organs that contain aggregates of lymphocytes.
The lymphoid organs are:
Primary lymphoid organs – bone marrow & thymus
Secondary lymphoid organs – lymph nodes, spleen, tonsils, Peyer’s patches, MALT (mucosa associated lymphoid tissue)

14. Lymphoid Organs Central Origin and main differentiation Thymus
Bone marrow
Spleen
Lymphoid nodes
Solitary nodules
Tonsils
Appendix
Peyer’s patches
Peripheral
Proliferation and
additional differentiation
Immune response

15. Lymphoid Organs Encapsulated Thymus Lymph nodes Spleen Unencapsulated
Diffuse
Tonsils
Diffuse lymphatic tissue is found in many regions of the body, especially beneath moist mucosal surface e.g trachea and intestine. There is absent of capsule and the lymphatic tissue merges with the surrounding connective tissue.

17. Thymus
A bilobed organ that secrets hormones (thymosin and thymopoietin) that cause T lymphocytes to become immunocompetent
The size of the thymus varies with age
In infants, it is found in the inferior neck and extends into the mediastinum where it partially overlies the heart
It increases in size and is most active during childhood
It stops growing during adolescence and then gradually atrophies

18. Thymus
The thymus differs from other lymphoid organs in important ways
It functions strictly in T lymphocyte maturation
It does not directly fight antigens
Function:
production of immunocompetent T lymphocytes
production of mature but naïve T cells for peripheral tissues and circulation
immunological self-tolerance
regulation of T cell maturation, proliferation and function via secretion of hormones

19. Internal Anatomy of the Thymus
Thymic lobes contain an outer cortex and inner medulla
The cortex contains densely packed lymphocytes and scattered macrophages
The medulla contains fewer lymphocytes and thymic (Hassall’s) corpuscles

20. Thymus

21. Thymic Cortex
Consists of proliferating lymphocytes dispersed among macrophages & epithelial reticular cells.
These epithelial cells/ reticular cells form the support structure for the developing T cells but also play an important role in isolating the T cells from foreign anitgens during their development
They are of endodermal origin & do not secrete reticular fibers.

24. Epithelial Reticular Cells
Endodermally derived.
Stellate eosinophilic cells with an oval nucleus.
Joined to adjacent reticular cells by desmosomes.
Enclose the developing lymphocytes within them.
Help in the formation of a blood-thymus barrier - prevents antigenic stimulation of the lymphocytes & allows for proper differentiation.
Secrete various hormones (thymulin, thymopoietin, thymosin & thymic humoral factor) that regulate T cell differentiation.

25. Blood Thymus barrier
Prevents premature exposure of lymphocytes to antigen (to inhibit tolerance).
The integrity of the  space within the epithelial cell framework is extremely important because it prevents the premature stimulation of T cells by antigens
Non-fenestrated endothelium with occluding junctions (major component of the barrier)
Endothelium
Thick basal lamina
Pericytes
Macrophages
Type I epithelioreticular cells

26. Blood Thymus barrier

27. Thymic Cortex
Contains maturing lymphocytes, macrophages & reticular cells.
Many lymphocytes die by apoptosis & are removed by macrophages.
Outer cortex is populated by immature lymphocytes & as they mature they migrate to the deeper part of the cortex.

28. Maturation of T cell in thymus
CORTEX
Epithelio reticular cell (RE)
MHC I
MHC II
Immature T cell
CD4
CD8
First T cell has to acquire markers CD4 and CD8
Cell without marker is destroyed
RE cell teaches the immature T cell to recognize the MHC markers
Some identify MHC I and some MHC II
T cell who don’t learn to identify either are destroyed
Immature T cell
CD4
CD8
MHC I
MEDULLA
T cells that recognize MHC I are destroyed or they lose CD4 from their surface
CD4 +ve
T cell
Immature T cell
CD4
CD8
MHC II
CD8 +ve
T cell

29. Thymic Medulla
Hassall’s corpuscles concentrically arranged, flattened epithelial reticular cells that become filled with keratin filaments, degenerate & may become calcified.
They appear in the fetus & their number gradually increases after birth.

30. QUESTION
The production of new T lymphocytes in the thymus occurs in which of the following regions?
Superficial cortex
Corticomedullary junction
Thymic nodules
Deep medulla
Thymic corpuscles

31. Lymph Node A filter: Removes: Initiation of immune response
purifies lymph before return to venous circulation
Removes:
debris
pathogens
99% of antigens
Initiation of immune response
Activation & proliferation of lymphocytes

32. Function of lymph nodes
filter debris and microorganisms via phagocytosis by fixed macrophages
facilitate the interaction between antigen presenting cells and circulating lymphocytes to initiate an immune response
B lymphocytes: activation and proliferation; plasma cell formation and antibody production in response to antigens
T lymphocytes: activation to become T helper and T cytotoxic cells

34. Lymphnode structure Afferent vessels – convey lymph towards the node
Efferent vessels – drain lymph away from the node at the hilum
Capsule
Trabeculae
Reticular tissue

36. Lymph node
Capsule
Subcapsular sinus

37. Structure of a Lymph Node (Cortex)
Superficial cortex: The cortex contains follicles with germinal centers, heavy with dividing B cells
Dendritic cells nearly encapsulate the follicles
Deep cortex houses T cells in transit
T cells circulate continuously among the blood, lymph nodes, and lymphatic stream

38. Lymph node

39. Lymphoid follicle
Germinal Center (GC) -  contains pale-staining cells. The open, pale-staining nature of the nuclei of these cells indicate that they are B lymphocytes undergoing active proliferation.
Other cells include:
Follicular dendritic cells that present antigen to the B cells
Macrophages that engulfed dead B cells that have died by apotosis

40. Lymphoid follicle cortex
Germinal center - Functional aspects: 
resting B cells enter the lymph node parenchyma though the high endothelial venules and if they encounter an antigen with which they can react, they then enter the cycle of blast transformation to produce clones of plasma cells and B memory cells.
This production of clones occurs in the germinal centers of lymphoid follicles.
Mantle zone (corona) –
The germinal center is surrounded by a ring of darker-staining cells.  The condensed nature of their nuclei indicates that these  are resting B cells. Also present in the mantle zone are T helper cells, macrophages and dendritic cells.

41. Paracortical zone / deep cortex
Paracortical zone - deeper regions of the cortex contain primarily T lymphocytes that do not form into follicles. 
T lymphocytes (helper and cytotoxic/suppresor) arrive through the circulation, enter the lymph node parenchyma through the high endothelial venules and take up residence in the paracortical zone. 
If activated, the T lymphocytes undergo active proliferation to produce expanded clones of activated T lymphocytes.  
Functional aspects:
T lymphocytes that arrive at the lymph node via the arterial blood stream gain access to the parenchyma of the lymph node through the wall of the high endothelial venules located in the paracortical zone. 
These blood vessels contain endothelial cells that are expressing specific lymphocyte binding molecules called addressins. 
These surface molecules are available to bind to lymphocytes that recognize them, the lymphoctyes bind to the surface of the endothelium, then cross the vessel wall and enter the lymph node parenchyma.

42. Homing of lymphocytes
A process by which lymphocytes return to lymph node by crossing walls of blood vessels, High endothelial venules- present in lymph nodes.

43. Lymph node architecture
HEV – specialized Post-capillary venules.
Cuboidal endothelium
Concentrates lymph
Receptors for antigen primed lymphocytes
*HEV- High endothelial venules

44. Structure of a Lymph Node (Medulla)
Medullary cords extend from the cortex and contain B cells, T cells, and plasma cells
The medullary cords are composed of  plasma cells producing  antibodies, their precursors, macrophages and T helper cells.
The most prominent cell in the cord is the precursor to plasma cells or immunoblasts that came from the germinal centers of the lymphoid follicles in the cortex of the node.
In the medullary cords, the plasma cells undergo final maturation and secrete antibodies into the lymph that is collected by efferent lymphatic vessels in the node and eventually carried to the general circulation.  Plasma cells may also get into the general circulation in this manner

45. Structure of a Lymph Node (Medulla)
The medullary sinuses are composed primarily of
reticular fibers (RF) providing the support framework,
reticular cells (fibroblast-like cells that secrete the reticulin) (RC) and 
macrophages. 

46. Lymph node – medullary cords

47. Medullary cords – reticulum stain

48. Lymphatic Disorders: Elephantiasis: parasite, roundworm
Lives in lymph nodes
Prevents fluid flow back to circulatory system
Chronic edema (fluid swelling)
Leads to thickening of skin
Autoimmune diseases
Failure of self tolerance
Immune system fails to recognize self antigens from foreign ones and attacks body’s own tissues
e.g Lupus
Young women more impacted usually
Autoimmune disease against DNA

49. Elephantiasis

50. Spleen
Part of the circulatory system with secondary immune system function
Functions
Reserve blood storage
Removal of aged cells
Immune-surveillance (hematogenous exposure to antigens)
Filters particulates from the blood (secondary to hepatic filter)

51. Structure of the Spleen
Fibrous capsule
Trabeculae that extend inward and contains lymphocytes, macrophages, and huge numbers of erythrocytes
Two distinct areas of the spleen are:
White pulp : area containing mostly lymphocytes suspended on reticular fibers and involved in immune functions
Red pulp : remaining splenic tissue concerned with disposing of worn-out RBCs and bloodborne pathogens

52. Spleen architecture

53. Spleen – Capsule Collagenous connective tissue
Smooth muscle (most prominent in ruminants and horses)
Allows contraction of the spleen
Large network of septa/trabeculae
Septa are framework through which vessels reach interior of spleen
Delicate reticular stroma

54. Splenic circulation

56. White Pulp – lymphiod Tissue
Periarteriolar lymphoid tissue (PALS)
Central artery coated by sheath of lymphocytes
Forms nodular lymphoid tissue
Has germinal centers
Supported by a fine specialized stroma

57. White pulp
The white pulp of the spleen is characterized by a parenchyma that consists of two types of lymphocytes, i.e., B cells and T cells located in two different areas of the spleen.  
B cells are located in the lymphoid follicles scattered throughout the organ. In younger animals, a germinal center can be seen as seen in lymph nodes. In fact, this type of white pulp functions much in the manner that lymphoid follicles of lymph nodes function, i.e., initiation of immune responses by B cells to foreign antigens in the blood. T cells are located around the central arteries and form a kind of sheath.  This site is called the periarteriolar lymphoid sheath.

58. In the micrograph above, white pulp of the spleen is seen in both locations: (1) a lymphoid follicle, outlined by the dashed line and (2) the PALS located around the central artery in which T cells are found.  The lymphoid follicle has a pale-staining germinal center (GC) in which B cells are proliferating.  Note the presence of a mantle zone (ManZ) that contains small lymphocytes and an outer marginal zone that contains larger lymphocytes that are less densely packed than cells in the mantle zone.   Outside the marginal zone is the red pulp.

59. In the micrograph above, white pulp of the spleen is seen in both locations: (1) a lymphoid follicle, outlined by the dashed line and (2) the PALS located around the central artery in which T cells are found.  The lymphoid follicle has a pale-staining germinal center (GC) in which B cells are proliferating.  Note the presence of a mantle zone (ManZ) that contains small lymphocytes and an outer marginal zone that contains larger lymphocytes that are less densely packed than cells in the mantle zone.   Outside the marginal zone is the red pulp.

60. Splenic follicle Same structure as cortical follicle in lymph node.
Germinal center
Mantle zone
Marginal zone
Form adjacent to PALS.

61. Splenic Cords and Sinuses
Make up the red pulp
Venous sinuses
Lined by phagocytic endothelial cells
Contain circulating blood
Cords are all the tissue inbetween
Contain RBCs, macrophages, lymphocytes, occasional neutrophils
Site where filtering function occurs
High number of nuclei compared to the sinuses

62. Red pulp
The red pulp of the spleen is characterized by a parenchyma (PN) that consists of macrophages of the sheathed capillaries as well as other macrophages and blood cells.  Occupied by numerous venous sinuses (VS). 
Sinuses are very open and can be easily traversed by blood cells.  Their lining consists of long endothelial cells (arrows) oriented along the longitudinal axis of the vessel. 
Large spaces occur between adjacent endothelial cells and the underlying basement membrane is discontinuous, thus blood cells can easily pass between the endothelial cells and gain access to the bloodstream on the venous side. 
Few fibroblasts responsible for producing the reticulin fibers; special stains are required to visualize the reticular network.

63. Splenic Red Pulp

64. Splenic red pulp
E=endothelial cell VS= venous sinuses

65. Splenic Macrophages Part of the MPS (macrophage phagocytic system)
Primary function is removal of “senescent” cells
Some are also antigen presenting cells (dendritic cells)

66. Lymphoid Tissue (Unencapsulated)
Diffuse lymphatic tissue
Scattered reticular tissue in every body organ
Larger collections in the lamina propria of mucous membranes and lymphoid organs
Mucosal associated lymphoid tissue (MALT)
Gut-associated (GALT)
Bronchial-associated (BALT)

67. Tonsils

68. Tonsils
Simplest lymphoid organs; form a ring of lymphatic tissue around the pharynx
Location of the tonsils
Palatine tonsils – either side of the posterior end of the oral cavity
Lingual tonsils – lie at the base of the tongue
Pharyngeal tonsil – posterior wall of the nasopharynx
Tubal tonsils – surround the openings of the auditory tubes into the pharynx

69. Tonsils
Lymphoid tissue of tonsils contains follicles with germinal centers
Tonsil masses are not fully encapsulated
Epithelial tissue overlying tonsil masses invaginates, forming blind-ended crypts
Crypts trap and destroy

71. Aggregates of Lymphoid Follicles
Peyer’s patches – isolated clusters of lymphoid tissue,
Found in the wall of the distal portion of the small intestine (Ileum)
Similar structures are found in the appendix
Appendix:
Destroy bacteria, preventing them from breaching the intestinal wall
Generate “memory” lymphocytes for long-term immunity

72. Peyer's patches - Ileum

73. MALT MALT – mucosa-associated lymphatic tissue is composed of:
Peyer’s patches, tonsils, and the appendix (digestive tract)
Lymphoid nodules in the walls of the bronchi (respiratory tract)
MALT protects the digestive and respiratory systems from foreign matter

74. Types of MALT and Functional aspects:
larger aggregates function much like lymph nodes
smaller, scattered MALT are mostly T lymphocytes but also have B cells and plasma cells      - mostly IgA in the intestines and respiratory tract to   protect against pathogens that may gain access to underlying tissues      - IgG and IgM secreted into lamina propria to counteract pathogens that have gained access to connective tissue      - IgE secreted into lamina propria; mediates the release of histamine from mast cells
single lymphocytes found within the lamina epithelial are mostly T lymphocytes
MALT is drained by efferent lymphatic's but there are no afferent lymphatic's
lymphocytes exposed in MALT regions go through regional lymph nodes then return to the MALT region after activation 

75. Organs of the Lymphatic System
Thymus
Houses developing lymphocytes
Secretes hormones that regulate lymphocyte activity
Shrinks with age
Lymph nodes
Concentrated near ear, mandible, neck, armpit, breasts, trachea, aorta, iliac crest, groin
Filter lymph, cleanse foreign matter
Remove impurities from fluid before return to blood
Spleen
Many RBC, lymphocytes, macrophages
Produces blood cells
Blood reservoir
Destroys old and bad RBC
Filter like lymph nodes
If removed, functions taken over by liver and bone marrow
Tonsils
Deal with ingested, foreign, inhaled pathogens
Many lymphocytes in tonsils

76. Q 2 Macrophages are directly involved in immune responses in which of
the following ways?
a. Production of IL-2
b. Presentation of antigen
c. Specific killing of tumor cells
d. Production of antibodies
e. Inactivation of helper T cells

77. Q 3
The mechanism for lymphocyte circulation from the lymphoid compartment
in the region marked with the asterisk to the blood involves
which of the following?

78. A. Homing receptors on lymphocytes that recognize vascular addressins on high endothelial venule cells
B. Lymphocyte binding to endothelial integrins followed by passage through endothelial cells lining the high endothelial postcapillary venules
C. Lymphocyte passage through the zonulae occludentes by diapedesis after dissolution of the junctions by proteolytic enzyme release
D. Lymphocyte passage from the efferent lymphatic vessel to the thoracic duct and subsequently the venous system
E. Passage of lymphocytes through the discontinuous sinusoidal wall into the blood

79. Q 4
This organ, shown at low magnification (A) and high magnification (B) is which of the following?

80. a. A site of antibody production
b. The site of filtration of the lymph and blood
c. Derived embryologically from the 3rd branchial arch
d. The site of production of CD4+ and CD8+ cells
e. A major site of red blood cell degradation and bilirubin recycling