HISTOLOGY OFHISTOLOGY OF

LYMPHOID ORGANSLYMPHOID ORGANS

INTRODUCTIONINTRODUCTION 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 Pre T Cell migrate to Thymus Stage 1: T cells with CD 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)

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 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 developing T 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 developing T Cells to blood-borne macromolecules

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

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 influence T cells

maturation : Corticosteroids decrease T cells number in

cortex Thyroxin stimulates epithelial reticular cells

to increase thymulin production Somatotropin promotes T 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 for T cells

LYMPH NODE 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 of T 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 Endothelial Venule (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/secon

dary nodules only in response of antigenic challenge

Reticular cells & fibero 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 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 surrounding A. 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

TONSILSTONSILS

Incompletely encapsulated aggregates of lymphoid nodules 1

Based on location : palatine, pharyngeal, lingual tonsils1

Produce lymphocytes1

PALATINE TONSILS 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 PA Abrahamsohn.)

PHARYNGEAL TONSILSPHARYNGEAL 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 than T. Palatina

LINGUAL TONSILSLINGUAL 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

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 by T 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