HISTOLOGY OFHISTOLOGY OFHISTOLOGY OFHISTOLOGY OFHISTOLOGY OFHISTOLOGY OFHISTOLOGY OFHISTOLOGY OF

LYMPHOID ORGANSLYMPHOID ORGANSLYMPHOID ORGANSLYMPHOID ORGANSLYMPHOID ORGANSLYMPHOID ORGANSLYMPHOID ORGANSLYMPHOID ORGANS

INTRODUCTIONINTRODUCTIONINTRODUCTIONINTRODUCTION• Immune systems consists of : 4

L h id– Lymphoid organs – Heterogeneous group of motile cell types

• 2 components of immune systems : 3I t I S t ifi ( l t– 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 C ll /APC )Cells/APCs)

4• Adaptive immune system : 4– Humoral immune response : B lymphocytes

produce antibodies phagocytosis & digestion of bacteria by macrophages & neutrophils leukocytesneutrophils leukocytes

A ll di t d i T– A cell-mediated immune response : T lymphocytes bind to surface of parasites or virus-infected cells lyse them by secreting avirus infected cells lyse them by secreting a membrane-disrupting protein & a Hydrolytic Enzymey

Lymphoid organs : 1, 3

• Primary/central organs : Thymus & Bone MarrowThymus & Bone Marrow responsible for development & maturation of lymphocytes y p y

• Secondary/Pheripheral organs : y p gLymph nodes, Spleen, Tonsils, solitary nodules, Peyer’s Patches of ileum, Appendix

Origin of Immune System CellsOrigin of Immune System Cells • Pluripotent hematopoetic stem cell in bone

marrow growth factors stimulation proliferation and maturation of the cellsformed elements of the blood

• Stem cell myeloid progenitor cell & y p glymphoid progenitor cells

• Lymphoid progenitor cells B lymphocytesLymphoid progenitor cells B lymphocytes & T lymphocytes

Growth factors on hematopoietic system p y• G-CSF, GM-CSF, M-CSF, IL- 1, IL-3, IL-4, IL-6,

EPO TPO etcEPO, TPO etc.• Cytokines are a unique family of growth factors

messenger molecules that can communicate signalsmessenger 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 diesecrete 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 andlymphocytes. B lymphocytes and natural killer lymphocytes are formed in the bone marrow and lea e the bone marro alreadleave the bone marrow already mature, to seed the secondary lymphoid organs and transit th h th bl d ith li dthrough the blood, epithelia, and connective tissues. Immature CD4–and CD8– T lymphocyte

t t d b thprecursors are transported by the blood circulation from the bone marrow to the thymus, where they

l t th i t ti dcomplete their maturation and leave as either CD4+ or CD8+ cells.

CLONAL SELECTION OF LYMPHOCYTES

• In bone marrow & Thymus primaryIn bone marrow & Thymus primary lymphoid organ

• Single type receptor on Lymphocytes can• Single type receptor on Lymphocytes can recognize all possible antigens but self tolerancetolerance

• Lymphocytes with receptors not self tolerance li i t d b t i l l d l tiare eliminated by apoptosis clonal deletion

B Lymphocytes MaturationB Lymphocytes Maturation

• Bone marro L mphoid stem cell Pro B• Bone marrow Lymphoid stem cell Pro B cell Pre B Cell Immature/naive B cells (Ig M) mature B Cells (Ig M + Ig D) bloodM) mature B Cells (Ig M + Ig D) blood stream & circulate secondary lymphoid organ

lif i d i f ll• Proliferation and maturation of B-cell responses are mediated by cytokines

T Cells MaturationT Cells Maturation

• Fetal liver/bone marrow Pre T Cell migrate to Thymus Stage 1: T cells with g y gCD 4- & CD8- (double negative) Stage 2: T Cells with CD 4+ & CD 8+ (Double positive) Stage 3 : mature T Cell with CD4+ or CD 8+ (single positive)

Approximate percentage of lymphocytes in l h id 1lymphoid organs1

Lymphoid organs

T lymphocytes %

B Lymphocytes %

Thymus 100 0

Bone marrow 10 90

Spleen 45 55

L h d 60 40Lymph nodes 60 40

Blood 80 20

THYMUS THYMUS THYMUS THYMUS • In superior mediastinum 1, 2

• 2 lobes Thin capsules septa subdivide into incomplete lobules 1, 3

• Each lobule consist of cortex & medulla:1,3medulla: ,

A.Cortex : • Darker than medulla due to

large number of T lymphocytes• Also contain macrophages &

E ith li l R ti l C llEpithelial Reticular Cells • 95-98% of developing T cells

die by apoptosis in cortex y p pphagocytosed by macrophages

B. Medulla : 1, 3

– Stain lighter than cortex less T cells population & large

b f ith li l ti lnumber of epithelial reticular cells

3 types of epithelial reticular– 3 types of epithelial reticular cells in medulla :

o Type IV cellso Type IV cells

o Type V cells

T VI ll H l’o Type VI cells Hassl’s Body / Thymic Corpuscle(found only in medulla, cornified, even calcified, unknown function)

Thymus vascular supply1, 3Thymus vascular supply• 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 developing T Cells topreventing contact of developing T Cells to blood-borne macromolecules

• Self macromolecules crossed barrier to select &• Self macromolecules crossed barrier to select & eliminate T cells react with self antigens clonal selection & clonal deletion

• No barrier in medulla• T cells leave medulla via veins drainning the thymusT cells leave medulla via veins drainning the thymus

Hormones in thymus 1, 3

• Epithelial reticular cells produce :– Thymosin– Thymopoietin– Thymulin

Th i h l f t– Thymic humoral factorFacilitate T cell proliferation & expression of surface

markers • Other hormones influence T cells maturation :

– Corticosteroids decrease T cells number in cortexh i i l i h li l i l ll i– Thyroxin stimulates epithelial reticular cells to increase

thymulin production– Somatotropin promotes T cells development in thymus p p p y

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 for T cells

LYMPH NODE LYMPH NODE LYMPH NODE LYMPH NODE • Kidney shape, encapsulated

(capsul of Conn. Tissue(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 of T cells, B cells, APCs & macrophages3

• On average, naive lymphocyte spend less than h i i l i b f h i½ hour in circulation before homing to

another lymphoid organ• 2 main ports of entry into Lymph Node :

– By High Endothelial Venule (HEV)• Specialized type of post capillary venule, lined by

cuboid or high endothelial cellsF d l i d l h id• Found only in secondary lymphoid organs except spleen

• Main site of B & T lymphocytes entry from bloodMain 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 Cortexo Outer Cortex• Lymphoid nodules

– B cells imunocytesB cells imunocytes– Germinal center/secondary

nodules only in response of antigenic challenge

• Reticular cells & fiber

I C t /P ti lo Inner Cortex/Paracortical Area T cells activated & proliferatedproliferated

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) i t di t i (5) d ll d (6)

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 stainintermediate sinus; (5) medullary cords; (6)

medullary sinus; (7) trabecula. H&E stain. Low magnification. (Courtesy of PA Abrahamsohn.)

tissue, and lymphatic nodules. H&E stain. Medium magnification. (Courtesy of PA Abrahamsohn.)

MEDULLA : 1, 2, 3

Medullary Cords :Medullary Cords :• B cells, plasma cells,

macrophages• Reticular cells & fiber• More irregular

trabeculae than in cortex

Medullary SinusMedullary Sinus continue with subcapsular sinus & pintermediate sinus end up in efferent lymph vesselsvessels

SPLEEN SPLEEN SPLEEN SPLEEN L t l h id i b d 3• Largest lymphoid organ in body 3

• Hilum • Capsul trabeculae• Capsul trabeculae• Consist of : 1, 2, 3

A. White Pulp :p• Formed by :

– Lymphoid nodules B cells

– Peri Arterial Lymphatic Sheath/PALS formed bySheath/PALS formed by T cells surrounding A. Centralis

• Lymphoid nodules germinal centre due to antigenic challenge

i l 3B. 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

l j l i i l i ti iti fplays major role in immunologic activities of spleen

C R d P l 1 3C. Red Pulp :1, 3

• Consist of :Splenic Cords / Billroth’sSplenic Cords / Billroth s Cords macrophages, T cells, B cells, plasma cells, blood cellsSplenic Sinusoids :

Endothelial cellsEndothelial cells fusiform, elongated Discontinuous basal lamina

Blood Circulation of Spleen

TONSILSTONSILSTONSILSTONSILS

• Incompletely encapsulated aggregates of lymphoid nodules 1

• Based on location : palatine, pharyngeal, lingual p , p y g , gtonsils1

• Produce lymphocytes1Produce lymphocytes

PALATINE TONSILS PALATINE TONSILS PALATINE TONSILS PALATINE TONSILS • A pair, in pars oralis

pharynx1

C i f 1 2 3• Consist of : 1, 2, 3

– Stratified squamous Epitheliump

– A band of lymphoid nodule with germinal centerC t– Crypts :

• Invagination of epithelium • 10-20 crypts/tonsil

Th l ti t il i t f diff l h t d• Contain food debris, dead leucocytes, desquamated of epithelial cells,bacteria etc

C l ti ll t th

The palatine tonsil consists of diffuse lymphocytes andlymphoid nodules disposed under a stratified squamousepithelium. One of the crypts of the tonsil is shown; thecrypts often contain dead epithelial and inflammatory cells.B: (1) Crypt; (2) stratified squamous epithelium; (3)lymphoid nodules; (4) diffuse lymphoid tissue; (5)– Capsule partially at the

baselymphoid nodules; (4) diffuse lymphoid tissue; (5)germinative center; (6) capsule; (7) mucous glands.Hematoxylin and eosin (H&E) stain. Low magnification.(Courtesy of PA Abrahamsohn.)

PHARYNGEAL TONSILSPHARYNGEAL TONSILSPHARYNGEAL TONSILSPHARYNGEAL TONSILS• Single in posterior nasopharynx1, 2

C i t f 1 2 3• Consist of :1, 2, 3

– Pseudostratified ciliated columar epithelium– Lymphoid nodules– No crypts, only shallow longitudinal infolding called

lpleats – Thinner capsule than T. Palatina

LINGUAL TONSILSLINGUAL TONSILSLINGUAL TONSILSLINGUAL TONSILS• Smaller & more numerous than other tonsils

LINGUAL TONSILSLINGUAL TONSILSLINGUAL TONSILSLINGUAL TONSILS

• At base of tongue• Consist of :1, 2, 3• Consist of : , , 3

– Stratified Squamous Epithelium L h id d l i l t– Lymphoid nodules germinal center

– Each lingual tonsils has a single crypts

MUCOSAMUCOSA--ASSOCIATED LYMPHOID ASSOCIATED LYMPHOID // 33

MUCOSAMUCOSA--ASSOCIATED LYMPHOID ASSOCIATED LYMPHOID // 33TISSUE TISSUE / / MALTMALT33TISSUE TISSUE / / MALTMALT33

• Non capsulated• Lymphoid nodules in

mucosa or submucosa of GI tract respiratory tracttract, respiratory tract, urinary tract.

• Gut-Associated lymphoidGut Associated lymphoid tissue (GALT) peyer’s patches (B Cells surround b T ll & APC ) Section of lung showing a collection of

lymphocytes in the connective tissue of the bronchiolar mucosa, an example of

i d l h id i

by T cells & APCs)• Bronchus-associated

lymphoid tissue (BALT) mucosa-associated lymphoid tissue (MALT). Pararosaniline—toluidine blue

(PT) stain. Low magnification.

lymphoid tissue (BALT) similar to peyer’s patches

REFERENCES :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 –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 PpKrausse PhD, Little Brown & Company (Inc), 1996. Pp 197-228

3. Color Textbook of Histologi, 2nd edition, Gartner LP, Hiatt JL WB S d C Phil d l hi P l iJL, 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