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)
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
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