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HISTOLOGY OF
LYMPHOID ORGANS
INTRODUCTION
 Immune systems consists of : 4
 Lymphoid organs
 Heterogeneous group of motile cell types
 2 components of immune systems : 3
 Innate Immune System  non spesific (complement,
macrophages & Neutrophils, Natural Killer cells/NK
cells)  nonclonal defense mechanism
 Adaptive Immune System  specific (T Lymphocytes, B
lymphocytes,Antigen Presenting Cells/APCs)
 Adaptive immune system : 4
 Humoral immune response : B lymphocytes
produce antibodies  phagocytosis & digestion
of bacteria by macrophages & neutrophils
leukocytes
 A cell-mediated immune response :T lymphocytes
bind to surface of parasites or virus-infected cells
 lyse them by secreting a membrane-disrupting
protein & a Hydrolytic Enzyme
Lymphoid organs : 1, 3
• Primary/central organs :Thymus
& Bone Marrow  responsible for
development & maturation of
lymphocytes
• Secondary/Pheripheral organs :
Lymph nodes, Spleen,Tonsils,
solitary nodules, Peyer’s Patches
of ileum, Appendix
Origin of Immune System
Cells
 Pluripotent hematopoetic stem cell in bone
marrow growth factors stimulation 
proliferation and maturation of the cells 
formed elements of the blood
 Stem cell  myeloid progenitor cell & lymphoid
progenitor cells
 Lymphoid progenitor cells  B lymphocytes &T
lymphocytes
Growth factors on hematopoietic
system
 G-CSF, GM-CSF, M-CSF, IL- 1, IL-3, IL-4, IL-6, EPO,
TPO etc.
 Cytokines are a unique family of growth factors 
messenger molecules that can communicate
signals from one cell type to another
 Secreted primarily from leukocytes but also produced by
various cells of the body  interleukin (IL)
 IL instruct the receiving cells to proliferate, differentiate,
secrete additional cytokines, migrate or die
 IL Stimulate both the humoral and cellular immune
responses, as well as the activation of phagocytic cells
 The list of identified interleukins grows continuously
Origin of the main types of
lymphocytes. B lymphocytes and
natural killer lymphocytes are
formed in the bone marrow and
leave the bone marrow already
mature, to seed the secondary
lymphoid organs and transit
through the blood, epithelia, and
connective tissues. Immature
CD4– and CD8–T lymphocyte
precursors are transported by the
blood circulation from the bone
marrow to the thymus, where
they complete their maturation
and leave as either CD4+ or CD8+
cells.
CLONAL SELECTION OF
LYMPHOCYTES
 In bone marrow &Thymus  primary lymphoid
organ
 Single type receptor on Lymphocytes can
recognize all possible antigens  but self
tolerance
 Lymphocytes with receptors not self tolerance
are eliminated by apoptosis  clonal deletion
B Lymphocytes Maturation
 Bone marrow  Lymphoid stem cell  Pro B cell
 Pre B Cell  Immature/naive B cells (Ig M)
mature B Cells (Ig M + Ig D)  blood stream &
circulate  secondary lymphoid organ
 Proliferation and maturation of B-cell responses are
mediated by cytokines
T Cells Maturation
 Fetal liver/bone marrow  PreT Cell 
migrate toThymus  Stage 1:T cells with CD
4- & CD8- (double negative)  Stage 2:T Cells
with CD 4+ & CD 8+ (Double positive)  Stage
3 : matureT Cell with CD4+ or CD 8+ (single
positive)
Lymphoid
organs
T lymphocytes
%
B Lymphocytes
%
Thymus 100 0
Bone marrow 10 90
Spleen 45 55
Lymph nodes 60 40
Blood 80 20
Approximate percentage of lymphocytes in
lymphoid organs1
THYMUS
 In superior mediastinum 1, 2
 2 lobes Thin capsules  septa 
subdivide into incomplete lobules 1, 3
 Each lobule consist of cortex &
medulla:1,3
A.Cortex :
• Darker than medulla  due to
large number of T lymphocytes
• Also contain macrophages &
Epithelial Reticular Cells
• 95-98% of developingT cells die
by apoptosis in cortex 
phagocytosed by macrophages
B. Medulla : 1, 3
– Stain lighter than cortex  less
T cells population & large
number of epithelial reticular
cells
– 3 types of epithelial reticular
cells in medulla :
o Type IV cells
o Type V cells
o Type VI cells  Hassl’s
Body / Thymic Corpuscle
(found only in medulla,
cornified, even calcified,
unknown function)
Thymus vascular supply1, 3
 Blood-thymus barrier  formed by continuous
cappillaries in cortex with thick basal lamina,
invested by sheath of type I epithelial reticular cells
 preventing contact of developingT Cells to
blood-borne macromolecules
 Self macromolecules crossed barrier  to select &
eliminateT cells react with self antigens  clonal
selection & clonal deletion
 No barrier in medulla
 T cells leave medulla via veins drainning the
thymus
Hormones in thymus 1, 3
 Epithelial reticular cells produce :
 Thymosin
 Thymopoietin
 Thymulin
 Thymic humoral factor
 Facilitate T cell proliferation & expression of surface
markers
 Other hormones influenceT cells maturation :
 Corticosteroids  decreaseT cells number in cortex
 Thyroxin  stimulates epithelial reticular cells to increase
thymulin production
 Somatotropin  promotesT cells development in thymus
cortex
THYMUS INVOLUTION4
 Start after puberty
 Parenchym replaced adipose
tissue and connective tissue
 Decrease weights : 40 g at
puberty, 10-15 g late in life
 After involution, thymus still
has its function as a maturation
place forT cells
LYMPH NODE
 Kidney shape, encapsulated
(capsul of Conn.Tissue
Trabeculae)
 Location : neck, axilla, scrotum,
blood vessels in thorax, etc 1, 2
 Have Afferent lymph vessel &
Efferent lymph vessel 1
 Hilum : concave depresion
which arteries & nerve enter,
veins & lymphatic vessels
leave1,2
 Parenchym composed ofT cells,
B cells, APCs & macrophages3
 On average, naive lymphocyte spend less than
½ hour in circulation before homing to another
lymphoid organ
 2 main ports of entry into Lymph Node :
 By High EndothelialVenule (HEV)
 Specialized type of post capillary venule, lined by
cuboid or high endothelial cells
 Found only in secondary lymphoid organs except
spleen
 Main site of B &T lymphocytes entry from blood  by
diapedesis
 By afferent lymph vessel  Site of some memory
cells, free antigens & or antigen-loaded APC
BLOOD & LYMPH CIRCULATION OF LYMPH NODE
CORTEX 1, 2
o Outer Cortex
 Lymphoid nodules
 B cells  imunocytes
 Germinal center/secondary
nodules  only in response
of antigenic challenge
 Reticular cells & fiber
o Inner Cortex/Paracortical Area 
T cells activated & proliferated
o Subcapsular Sinus &
intermediate/Peritrabekular
Sinus
Section of a lymph node showing the cortex
and the medulla and their primary
components. B: (1) Capsule; (2) lymphoid
nodule with germinative center; (3) subcapsular
sinus; (4) intermediate sinus; (5) medullary
cords; (6) medullary sinus; (7) trabecula. H&E
stain. Low magnification. (Courtesy of PA
Abrahamsohn.)
Section of a portion of the outer cortex of a
lymph node showing the capsule,
subcapsular sinuses, diffuse lymphoid
tissue, and lymphatic nodules. H&E stain.
Medium magnification. (Courtesy of PA
Abrahamsohn.)
MEDULLA : 1, 2, 3
Medullary Cords :
 B cells, plasma cells,
macrophages
 Reticular cells & fiber
 More irregular
trabeculae than in
cortex
Medullary Sinus 
continue with subcapsular
sinus & intermediate sinus
end up in efferent
lymph vessels
SPLEEN
 Largest lymphoid organ in body 3
 Hilum
 Capsul  trabeculae
 Consist of : 1, 2, 3
A. White Pulp :
 Formed by :
 Lymphoid nodules  B cells
 Peri Arterial Lymphatic
Sheath/PALS  formed by
T cells surroundingA.
Centralis
 Lymphoid nodules  germinal
centre due to antigenic
challenge
B. Marginal zone 3
 Separate white pulp to red pulp
 Composed of plasma cells,T cells, B cells,
macrophages,APCs
 Marginal sinuses
 Contain an abundance of blood antigens 
plays major role in immunologic activities of
spleen
C. Red Pulp :1, 3
• Consist of :
 Splenic Cords / Billroth’s
Cords  macrophages,T
cells, B cells, plasma cells,
blood cells
 Splenic Sinusoids :
 Endothelial cells
fusiform, elongated
 Discontinuous basal
lamina
Blood Circulation of Spleen
TONSILS
 Incompletely encapsulated aggregates of
lymphoid nodules 1
 Based on location : palatine, pharyngeal, lingual
tonsils1
 Produce lymphocytes1
PALATINE TONSILS
 A pair, in pars oralis
pharynx1
 Consist of : 1, 2, 3
 Stratified squamous
Epithelium
 A band of lymphoid nodule
with germinal center
 Crypts :
 Invagination of epithelium
 10-20 crypts/tonsil
 Contain food debris, dead
leucocytes, desquamated of
epithelial cells,bacteria etc
 Capsule  partially at the
base
The palatine tonsil consists of diffuse lymphocytes and
lymphoid nodules disposed under a stratified squamous
epithelium. One of the crypts of the tonsil is shown; the
crypts often contain dead epithelial and inflammatory cells.
B: (1) Crypt; (2) stratified squamous epithelium; (3)
lymphoid nodules; (4) diffuse lymphoid tissue; (5)
germinative center; (6) capsule; (7) mucous glands.
Hematoxylin and eosin (H&E) stain. Low magnification.
(Courtesy of PAAbrahamsohn.)
PHARYNGEAL TONSILS
 Single in posterior nasopharynx1, 2
 Consist of :1, 2, 3
 Pseudostratified ciliated columar epithelium
 Lymphoid nodules
 No crypts, only shallow longitudinal infolding called
pleats
 Thinner capsule thanT. Palatina
LINGUAL TONSILS
 Smaller & more numerous than other tonsils
 At base of tongue
 Consist of :1, 2, 3
 Stratified Squamous Epithelium
 Lymphoid nodules  germinal center
 Each lingual tonsils has a single crypts
MUCOSA-ASSOCIATED LYMPHOID TISSUE /
MALT3
Section of lung showing a collection of
lymphocytes in the connective tissue of
the bronchiolar mucosa, an example of
mucosa-associated lymphoid tissue
(MALT). Pararosaniline—toluidine blue
(PT) stain. Low magnification.
 Non capsulated
 Lymphoid nodules in
mucosa or submucosa of
GI tract, respiratory tract,
urinary tract.
 Gut-Associated lymphoid
tissue (GALT)  peyer’s
patches (B Cells surround
byT cells & APCs)
 Bronchus-associated
lymphoid tissue (BALT) 
similar to peyer’s patches
REFERENCES :
1. Basic Histology Text & Atlas , 10th ed. , L. Carlos
Junquira MD, Jose Carneiro MD, Robert O. Kelley PhD,
Lange Medical Books, Mc Graw-Hill , 2003. Pp 265 –
290.
2. Essentials of Human Histology, 2nd Edition, William J.
Krausse PhD, Little Brown & Company (Inc), 1996. Pp
197-228
3. Color Textbook of Histologi, 2nd edition, Gartner LP, Hiatt
JL, WB Saunders Company, Philadelphia, Pennsylvania,
2001. Pp 273-299
4. Consise Histology, 2nd edition, Don W Fawcett, Ronald P
Jensh, Arnold publisher, London, 2002. Pp 148-161

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Lymphoid organs

  • 2. INTRODUCTION  Immune systems consists of : 4  Lymphoid organs  Heterogeneous group of motile cell types  2 components of immune systems : 3  Innate Immune System  non spesific (complement, macrophages & Neutrophils, Natural Killer cells/NK cells)  nonclonal defense mechanism  Adaptive Immune System  specific (T Lymphocytes, B lymphocytes,Antigen Presenting Cells/APCs)
  • 3.  Adaptive immune system : 4  Humoral immune response : B lymphocytes produce antibodies  phagocytosis & digestion of bacteria by macrophages & neutrophils leukocytes  A cell-mediated immune response :T lymphocytes bind to surface of parasites or virus-infected cells  lyse them by secreting a membrane-disrupting protein & a Hydrolytic Enzyme
  • 4. Lymphoid organs : 1, 3 • Primary/central organs :Thymus & Bone Marrow  responsible for development & maturation of lymphocytes • Secondary/Pheripheral organs : Lymph nodes, Spleen,Tonsils, solitary nodules, Peyer’s Patches of ileum, Appendix
  • 5. Origin of Immune System Cells  Pluripotent hematopoetic stem cell in bone marrow growth factors stimulation  proliferation and maturation of the cells  formed elements of the blood  Stem cell  myeloid progenitor cell & lymphoid progenitor cells  Lymphoid progenitor cells  B lymphocytes &T lymphocytes
  • 6. Growth factors on hematopoietic system  G-CSF, GM-CSF, M-CSF, IL- 1, IL-3, IL-4, IL-6, EPO, TPO etc.  Cytokines are a unique family of growth factors  messenger molecules that can communicate signals from one cell type to another  Secreted primarily from leukocytes but also produced by various cells of the body  interleukin (IL)  IL instruct the receiving cells to proliferate, differentiate, secrete additional cytokines, migrate or die  IL Stimulate both the humoral and cellular immune responses, as well as the activation of phagocytic cells  The list of identified interleukins grows continuously
  • 7. Origin of the main types of lymphocytes. B lymphocytes and natural killer lymphocytes are formed in the bone marrow and leave the bone marrow already mature, to seed the secondary lymphoid organs and transit through the blood, epithelia, and connective tissues. Immature CD4– and CD8–T lymphocyte precursors are transported by the blood circulation from the bone marrow to the thymus, where they complete their maturation and leave as either CD4+ or CD8+ cells.
  • 8. CLONAL SELECTION OF LYMPHOCYTES  In bone marrow &Thymus  primary lymphoid organ  Single type receptor on Lymphocytes can recognize all possible antigens  but self tolerance  Lymphocytes with receptors not self tolerance are eliminated by apoptosis  clonal deletion
  • 9. B Lymphocytes Maturation  Bone marrow  Lymphoid stem cell  Pro B cell  Pre B Cell  Immature/naive B cells (Ig M) mature B Cells (Ig M + Ig D)  blood stream & circulate  secondary lymphoid organ  Proliferation and maturation of B-cell responses are mediated by cytokines
  • 10. T Cells Maturation  Fetal liver/bone marrow  PreT Cell  migrate toThymus  Stage 1:T cells with CD 4- & CD8- (double negative)  Stage 2:T Cells with CD 4+ & CD 8+ (Double positive)  Stage 3 : matureT Cell with CD4+ or CD 8+ (single positive)
  • 11. Lymphoid organs T lymphocytes % B Lymphocytes % Thymus 100 0 Bone marrow 10 90 Spleen 45 55 Lymph nodes 60 40 Blood 80 20 Approximate percentage of lymphocytes in lymphoid organs1
  • 12. THYMUS  In superior mediastinum 1, 2  2 lobes Thin capsules  septa  subdivide into incomplete lobules 1, 3  Each lobule consist of cortex & medulla:1,3 A.Cortex : • Darker than medulla  due to large number of T lymphocytes • Also contain macrophages & Epithelial Reticular Cells • 95-98% of developingT cells die by apoptosis in cortex  phagocytosed by macrophages
  • 13. B. Medulla : 1, 3 – Stain lighter than cortex  less T cells population & large number of epithelial reticular cells – 3 types of epithelial reticular cells in medulla : o Type IV cells o Type V cells o Type VI cells  Hassl’s Body / Thymic Corpuscle (found only in medulla, cornified, even calcified, unknown function)
  • 14. Thymus vascular supply1, 3  Blood-thymus barrier  formed by continuous cappillaries in cortex with thick basal lamina, invested by sheath of type I epithelial reticular cells  preventing contact of developingT Cells to blood-borne macromolecules  Self macromolecules crossed barrier  to select & eliminateT cells react with self antigens  clonal selection & clonal deletion  No barrier in medulla  T cells leave medulla via veins drainning the thymus
  • 15. Hormones in thymus 1, 3  Epithelial reticular cells produce :  Thymosin  Thymopoietin  Thymulin  Thymic humoral factor  Facilitate T cell proliferation & expression of surface markers  Other hormones influenceT cells maturation :  Corticosteroids  decreaseT cells number in cortex  Thyroxin  stimulates epithelial reticular cells to increase thymulin production  Somatotropin  promotesT cells development in thymus cortex
  • 16. THYMUS INVOLUTION4  Start after puberty  Parenchym replaced adipose tissue and connective tissue  Decrease weights : 40 g at puberty, 10-15 g late in life  After involution, thymus still has its function as a maturation place forT cells
  • 17. LYMPH NODE  Kidney shape, encapsulated (capsul of Conn.Tissue Trabeculae)  Location : neck, axilla, scrotum, blood vessels in thorax, etc 1, 2  Have Afferent lymph vessel & Efferent lymph vessel 1  Hilum : concave depresion which arteries & nerve enter, veins & lymphatic vessels leave1,2  Parenchym composed ofT cells, B cells, APCs & macrophages3
  • 18.  On average, naive lymphocyte spend less than ½ hour in circulation before homing to another lymphoid organ  2 main ports of entry into Lymph Node :  By High EndothelialVenule (HEV)  Specialized type of post capillary venule, lined by cuboid or high endothelial cells  Found only in secondary lymphoid organs except spleen  Main site of B &T lymphocytes entry from blood  by diapedesis  By afferent lymph vessel  Site of some memory cells, free antigens & or antigen-loaded APC
  • 19. BLOOD & LYMPH CIRCULATION OF LYMPH NODE
  • 20. CORTEX 1, 2 o Outer Cortex  Lymphoid nodules  B cells  imunocytes  Germinal center/secondary nodules  only in response of antigenic challenge  Reticular cells & fiber o Inner Cortex/Paracortical Area  T cells activated & proliferated o Subcapsular Sinus & intermediate/Peritrabekular Sinus
  • 21. Section of a lymph node showing the cortex and the medulla and their primary components. B: (1) Capsule; (2) lymphoid nodule with germinative center; (3) subcapsular sinus; (4) intermediate sinus; (5) medullary cords; (6) medullary sinus; (7) trabecula. H&E stain. Low magnification. (Courtesy of PA Abrahamsohn.) Section of a portion of the outer cortex of a lymph node showing the capsule, subcapsular sinuses, diffuse lymphoid tissue, and lymphatic nodules. H&E stain. Medium magnification. (Courtesy of PA Abrahamsohn.)
  • 22. MEDULLA : 1, 2, 3 Medullary Cords :  B cells, plasma cells, macrophages  Reticular cells & fiber  More irregular trabeculae than in cortex Medullary Sinus  continue with subcapsular sinus & intermediate sinus end up in efferent lymph vessels
  • 23. SPLEEN  Largest lymphoid organ in body 3  Hilum  Capsul  trabeculae  Consist of : 1, 2, 3 A. White Pulp :  Formed by :  Lymphoid nodules  B cells  Peri Arterial Lymphatic Sheath/PALS  formed by T cells surroundingA. Centralis  Lymphoid nodules  germinal centre due to antigenic challenge
  • 24. B. Marginal zone 3  Separate white pulp to red pulp  Composed of plasma cells,T cells, B cells, macrophages,APCs  Marginal sinuses  Contain an abundance of blood antigens  plays major role in immunologic activities of spleen
  • 25. C. Red Pulp :1, 3 • Consist of :  Splenic Cords / Billroth’s Cords  macrophages,T cells, B cells, plasma cells, blood cells  Splenic Sinusoids :  Endothelial cells fusiform, elongated  Discontinuous basal lamina
  • 27. TONSILS  Incompletely encapsulated aggregates of lymphoid nodules 1  Based on location : palatine, pharyngeal, lingual tonsils1  Produce lymphocytes1
  • 28. PALATINE TONSILS  A pair, in pars oralis pharynx1  Consist of : 1, 2, 3  Stratified squamous Epithelium  A band of lymphoid nodule with germinal center  Crypts :  Invagination of epithelium  10-20 crypts/tonsil  Contain food debris, dead leucocytes, desquamated of epithelial cells,bacteria etc  Capsule  partially at the base The palatine tonsil consists of diffuse lymphocytes and lymphoid nodules disposed under a stratified squamous epithelium. One of the crypts of the tonsil is shown; the crypts often contain dead epithelial and inflammatory cells. B: (1) Crypt; (2) stratified squamous epithelium; (3) lymphoid nodules; (4) diffuse lymphoid tissue; (5) germinative center; (6) capsule; (7) mucous glands. Hematoxylin and eosin (H&E) stain. Low magnification. (Courtesy of PAAbrahamsohn.)
  • 29. PHARYNGEAL TONSILS  Single in posterior nasopharynx1, 2  Consist of :1, 2, 3  Pseudostratified ciliated columar epithelium  Lymphoid nodules  No crypts, only shallow longitudinal infolding called pleats  Thinner capsule thanT. Palatina
  • 30. LINGUAL TONSILS  Smaller & more numerous than other tonsils  At base of tongue  Consist of :1, 2, 3  Stratified Squamous Epithelium  Lymphoid nodules  germinal center  Each lingual tonsils has a single crypts
  • 31. MUCOSA-ASSOCIATED LYMPHOID TISSUE / MALT3 Section of lung showing a collection of lymphocytes in the connective tissue of the bronchiolar mucosa, an example of mucosa-associated lymphoid tissue (MALT). Pararosaniline—toluidine blue (PT) stain. Low magnification.  Non capsulated  Lymphoid nodules in mucosa or submucosa of GI tract, respiratory tract, urinary tract.  Gut-Associated lymphoid tissue (GALT)  peyer’s patches (B Cells surround byT cells & APCs)  Bronchus-associated lymphoid tissue (BALT)  similar to peyer’s patches
  • 32. REFERENCES : 1. Basic Histology Text & Atlas , 10th ed. , L. Carlos Junquira MD, Jose Carneiro MD, Robert O. Kelley PhD, Lange Medical Books, Mc Graw-Hill , 2003. Pp 265 – 290. 2. Essentials of Human Histology, 2nd Edition, William J. Krausse PhD, Little Brown & Company (Inc), 1996. Pp 197-228 3. Color Textbook of Histologi, 2nd edition, Gartner LP, Hiatt JL, WB Saunders Company, Philadelphia, Pennsylvania, 2001. Pp 273-299 4. Consise Histology, 2nd edition, Don W Fawcett, Ronald P Jensh, Arnold publisher, London, 2002. Pp 148-161