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Lymphatic System Organs

DR KIRTI SOLANKE

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INTRODUCTION

• Not a primary tissue type but a variety of connective tissue.

• Components-1.lymphatic vessels2.lymphatic organs3.cells4.lymph

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Primary Lymphatic Organs and Tissues

• The primary (central) lymphatic organs and tissues include the thymus, bone marrow and gut associated lymphatic tissue (GALT).

• They are sites of – antigen-independent proliferation, and– differentiation into cells pre-programmed to

recognise specific antigens. • These immunocompetent cells then enter the

blood and lymph:– get dispersed in the connective tissue and – penetrate into epithelia that line mucosal surfaces.

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Secondary Lymphatic Organs and Tissues

• These are the effector lymphatic tissues. • They include the lymphatic nodules, lymph

nodes, tonsils and the spleen. • Here lymphocytes undergo antigen-

dependent proliferation and differentiation into effector lymphocytes and memory cells.

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Lymphatic capillaries are not ubiquitous-absent in cornea, cartilage, thymus, central and peripheral

nervous sys & bone marrow.Lymphatic circulation

• Deep• Valves closely placed• Blind ends• No pericytes• Irregular shape in cut sec.• Basal lamina incomplete• Greater caliber

Vascular circulation

• Superficial• Less closely placed• Both ends open• Pericyte• Cylindrical form• Continuous• Less caliber

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LYMPH• Lighter specific gravity

than blood• Contains no

RBCs,platelets,fibrinogen but it contains numerous Lymphocytes.

• Lymphocytes are added when it passes through LN.

• Coagulate at much slower rate than blood

• Does not carry O2 but may contain CO2.

• Chyle-fat globules, lacteal

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• Lymph vessels of- thyroid gland-oesophagus-coronary and triangular ligaments of liver

may drain directly into thoracic duct.

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Functions of lymphoid system

1) To maintain – pressure & -volume of extracellular fluid by

returning excess water to the circulation. 2) The site of clonal production of

immunocompetent lymphocytes and macrophages in the specific immune response.

CELLS OF LYMPHATIC SYSTEMChief cells are lymphocytes-type of WBC’S.• B lymphocytes• T lymphocytes• Natural killer cells• epithelioreticular cells - MESENCHYMAL • Supporting cells-

– interact with lymphocyte– Present antigens to Lymphocytes

• OTHER TYPE OF WBC’S-monocyte

-macrophages-neutruphils

-eosinophils -basophils

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• ANTIGEN PRESENTING CELLS– dendriti cells-Bone marrow derived – follicular cells– langerhan’s cells

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Derivation and Distribution of Lymphocytes

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T Lymphocytes

• These evolve in the thymus • part of the cell-mediated or thymus-

dependent response to antigens. • Upon interaction with an antigen, they will

differentiate and proliferate into - 3 types of effector T lymphocytes:

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1.Cytotoxic lymphocytes (killer T cells) (primary effector cells in cell-mediated immunity.)scan the surface of other cells for signs of viral infection or abnormality, killing them if necessary by causing them to lyse.

2.Helper T lymphocytes, recognise foreign antigens presented by macrophages. release interleukin hormones to stimulate ‘processed’ B

cells to produce antibodies. 3.Suppresser T lymphocytes, suppress the activity of B

cells.

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HELPER T CELL SUBTYPES(CYTOKINES)• Th1 cell• interact with cytotoxic

CD8,NK ,macrophages.• CMI• For controling

intracellular pathogens• Viruses &

microorganisms.

• IL 2,Interferon gamma

• Th2 cells• interact with B

lymphocyte• HIR• Exracellular pathogens

• IL4, 5 ,10,13.

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B Lymphocytes

• These evolve in bone marrow and GALT, and are part of the humoral response.

• They will only react with the antigen they have been genetically programmed for.

• Once activated by this antigen, they may differentiate and proliferate into either:

• Plasma cells, that produce antibodies.

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• The antibody binds, forming an antibody-antigen complex, that may be phagocytosed by macrophages.

• Memory cells, which, after exposure to the

specific antigen, will be able to participate in a rapid, secondary response with the same antigen.

• They do not participate in an initial or primary response.

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– Prog In Thymus– Long life span– For CMI– Graft Rejection– 60% to 8o%– CD 2,CD3,CD7– T cell receptors(TCRs)– CD4,CD8

B – Lymphocytes

– Prog In B M– Variable lifespan– For H.I.– Plasma Cells – Ab– 20 to 30%– CD9,CD19,CD20 & CD24– Bcell receptors– MHC II

T-Lymphocyte

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NK LYMPHOCYTE/NULL CELLS

• Neither T nor B cells• Specialised to kill certain types of target cells• 5 to 10% • Do not mature in thymus• Kill in the same way as that of CTLS• After recognition of tranformed cell,secrete

perforins & fragmentins• CD 56, CD94.

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Macrophages

• These are involved in both types of immune response.

• They can process and present the antigen to the B cells or helper T cells.

• Or they can destroy the antigen by digestion after it has been processed by other cells of the immune system.

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CLASSIFICATIONI. FUNCTIONAL

LYMPHOID ORGANS

CENTRAL PERIPHERAL

THYMUS

BONE MARROW

LYMPH NODE

SPLEEN

MALT, GALT

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II. MORPHOLOGICAL

LYMPHOID ORGANS

DISCRETE DIFFUSE

LN, SPLEENTHYMUS, TONSIL

BM, PEYER’S PATCHES

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LYMPH NODE• Oval/Kidney Shape, 0.1 – 0.5cm Long• Normal young body contains up to 450,of which 60

to 70 in head and neck,100 in thorax,250 in abd& pelvis

• Greatest no. lie close to the viscera mainly mesenteries.

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Lymph Node: Gross Appearance

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• Capsule – Trabeculae, hilus-collagenous framework

• Lymph flow– Retculin Meshwork-sinuses– Subcapsular Sinus– Cortical Sinuses– Medullary Sinuses– Eff Lymph Ch

• Cortex medulla-diff in arrangement

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• Role of germinal centre-affinity maturation

• Two zones in GC-dark zone-centroblast-undergoing rapid proliferation-hypermaturation of their antibody mol.

• light zone-centrocytes-ineract with the FDC-carrying unprocessed antigen on their surface.

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Lymph Node

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Lymph Node

A - Afferent lymphatic channelsB - Subcapsular sinusC - FollicleD - SinusesE - Paracortical regionF - Medullary cordsG - Efferent lymphatic channel

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Variations in nodes

• In large nodes –trabeculae are prominent• In small nodes-thin and frequently interrupted• Hemal nodes• lymphadenitis

• Diffusely distributed lymphatic nodules represent local immune response to antigen that are present in tissue fluid.

• LN-lymph.• Spleen-circulating blood-mainly HIR.

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The Spleen • The spleen is the largest

lymphatic organ, located in the upper left quadrant of the abdominal cavity.

• The spleen functions to filter the blood, and react immunologically to blood-borne antigens mainly HIR,to dispose of defective blood cells,store blood cells &platelets,hematopoiesis

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Structure of the Spleen

• There is an external capsule of dense connective tissue.

• trabeculae extend into the substance of the organ. • myofibroblasts, and is thus contractile. • medial surface of the spleen, the hilum allows

passage of the splenic vessels, nerves and lymphatic vessels.

• The substance of the spleen is known as the splenic pulp.

• white pulp areas,• surrounded by red pulp.

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Spleen

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The White Pulp • This mainly consists of lymphocytes. • Branches of the splenic artery course through

the trabeculae and then enter the white pulp, known as the central artery

• The lymphocytes aggregated around the central artery in a cylindrical fashion -periarterial lymphatic sheath (PALS) of the artery.

• Lymph nodules in the PALS may displace the central artery from its central position in the white pulp.

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The Red Pulp

• This has large numbers of red blood cells (RBCs).

• It consists of splenic sinuses, separated by splenic cords (of Billroth).

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Spleen

SPLENIC A

SEGMENTAL A

TRABECULAR A

CENTRAL A

FOLLICULAR A

PENICILLAR A

ELLIPSOIDS

PRE CAPILLARY A

SINUSOIDS

TRABECULAR VEINS

SPLENIC VEIN

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Splenic Circulation • The splenic artery branches into the

trabecular, the central arteries. • The central arteries of the white pulp then

branch into penicillar arterioles in the red pulp.

• These are actually capillaries, and may be sheathed by aggregations of macrophages.

• Blood from these penicilli leaves the vascular system to populate the splenic pulp, before re-entering the red pulp.

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Two theories • Closed Circulation Model • In this model, the splenic arterioles are a "continuous vascular

channel". • They only empty into the splenic sinuses of the red pulp. • The blood then leaves the sinuses before re-entering them. • • Open Circulation Model • In this model, the arterioles empty directly into the splenic cords. • Thus, blood percolates through the reticular meshwork of the

pulp. • It then only enters the splenic sinuses from the extravascular side. • This model has more supporting evidence than the former.• FUNCTIONS

THYMUS

• Introduction• Gross anatomy• development• Histology -Circulation -Relation with

immunology• Functions• Age changes• Recent advances

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The Thymus (neuroendocrine organ)• The thymus -4-6 cm long

2.5-5 cm wide1cm thick,20 gmbi-lobed organ

• left lobe higher superior mediastinum,

anterior to the heart and great vessels

• Thyrothymic ligament• b/d supply-inf thyroid A,Internal

thorasic A.• Lymphatics-

parasternal,brachiocephalic,tracheobronchial

Structural components

• Stroma-capsule -trabeculae

• Parenchyma –epithelioreticular cells -lymphocytes -macrophages -mast cells

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Development

• 3rd &4th endodermal pouch-epithelial reticular cells

• Local cardiac neural crest mesenchyme control dev of gland.

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Development

• .

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Histology

• Important environment-acquiring immune tolerance

• Dev of T lymphocyte-interaction between-thymocyte &-epithelioreticular

cells,APC,chemical factors• Capsule-incomplete trabeculae-irregular

lobule-0.5-2mm in dia.

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Thymus

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CIRCULATION

• Thymic cortex and medulla functionally independent.

lymphoid stem cells from BM outer cortex progeny proliferate & differentiat

inner cortex medullary venules at CM junction.

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cortex• Dark staining-small L• Less in no

• Plasma cells absent• b/d supply mainly by

capillaries

medulla• Paler staining-large L• Macropgages,dendritic cells

are more • Plasma cells present• Mainly thymic A,arteriole

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Epithelioreticular cells• Parenchyma: epithelioreticular cells.

– are epithelial cells having stellate shape – form cytoplasmic reticulum: a framework for the

thymic lymphocytes. – correspond to the other reticular cells in lymphatic

tissues, – but no reticular fibres in the thymus. – Feature of both epithelial (intercellular junctions,

intermediate filament)and reticular cells(framework)--thymic nurse

cells– crosstalk

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Epithelioreticular cells• 6 types• Type l-boundary of capsule & cortex• Type ll-within cortex, compartmentalize the

cortex• Type lll-between cortex and medulla• Type lV –b/w cortex & medulla,barrier at CM

junction• Type V-like type ll in cortex• Type lV – corpuscles, keratohyaline granules,

produce lL-4&7.

OTHER CELLS• Myeloid lineage-monocyte• Macrophages-PAS cells• Fibroblast• Myoid cells• Hassall’s corpuscles-distinguishing feature of thymic

medulla.30-100μm in dia. IL-4,IL-7;named after Arthur Hill Hassall British physician

• Plasma cells are rare in cortex.• adipocytes

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HASSALL’S CORPUSCLES

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THYMIC HORMONES

• epithelial reticular cells -1.thymopoietin2.thymosin alpha

Induce expression of T lymphocyte surface markers

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THYMIC BARRIER• No afferent lymphatics• Physical barrier-Capillary endothelium -Endothelial basal lamina - pericyte

-thin perivascular connective tissue sheath with macrophages

- Basal lamina of the epithelioreticular cells

- Epithelioreticular cell sheath

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Changes of Thymic Structure with Age(involution)

• Largest at birth• fully functional at 20 weeks of foetal life. • progressive involution of adipose tissue.

– Accelerated by adrenal corticosteroids and sex hormones • In juveniles:

– isolation of cortical compartments, – reduction of cortical and medullary volume, and – appearance of more, larger blood vessels,

• until the adult thymus is mainly dominated by fat.

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Thymus

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Applied

• Myasthenia gravis• Yellow fever vaccine• DiGeorge syndrome-absent-thymus &

parathyroid ,defect in cardiac outflow tract

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QUANTIFICATION OF THYMIC FUNCTION

• RTE (Recent thymic emigrant)-– newly produced peripheral naive T cells – retain some phenotypic signature of recent thymic

maturation – distinguishes them from long lived

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THANK YOU

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APPLIED-should ask about a history of thymus disorder or dysfunction,

irrespective of age, including myasthenia gravis, thymoma, thymectomy, or DiGeorge syndrome, before administering

yellow fever vaccine.(Barwick RS, Marfin AA, Cetron MS. Yellow fever vaccine-associated disease.

In: . Washington: ASM Press, 2004: 25-34 vaccine was not one of the live vaccines assessed in the study.)

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Involution of the thymusAfter puberty much of the parenchyma of the thymus, in particular cortical lymphoid tissue, is replaced by adipose tissue. The process, which is called

involution, initially proceeds rapidly but slows down in adulthood. Involution is under the control of steroid hormones (both sexual hormones and stress

hormones). Although most pronounced in the thymus, involution is a common feature of all lymphoid tissues.

Another age-related phenomenon is the increase in size of the thymic (or Hassall's) corpuscles. Thymic corpuscles are rounded eosinophilic structures, which consist of concentrically arranged, flattened cells. Thymic corpuscles are likely to be formed by reticular cells. Similar structures occur also in the tonsils. The size of these structures varies from 20 µm to more than 100 µm in diameter. Thymic corpuscles may calcify, and their core may "dissolve"

leading to the formation of a cyst.

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DIFFUSE LYMPHATIC ORGANS

• Lymphatic nodules-solitary lymphatic nodules -temporary structers -in the lamina propria

• Permanent aggregates

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PALATINE TONSIL

• Shape,location,bed of palatine• Waldeyer’s ring

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LYMPHATIC NODULES/FOLLICLES• In the lamina propria aggregations of small

lymphocytes-a form of uncapulated lymphatic tissue

• Follicular associated epithelium-covering mucosa-associated L T.

• In small & large intestine these specialised cell have characterised short microvilli on their luminal surface called micrifold (M) cells

• In palatine tonsils-modified stratified squamous reticulated epithelial cells.

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Gut Associated Lymphoid Tissue• In the lamina propria and submucosal of the gastrointestinal

tract from the tongue to the colon are collections of lymphoid tissue. In some areas, the lymphoid tissue is more prominent:

– Lingual Tonsil: at the posterior tongue are larger collections of lymphoid tissue.

– Pharyngeal Tonsil: these are the structures commonly called "tonsils" and comprise tissues functionally equivalent to lymph nodes.

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Gut Associated Lymphoid Tissue

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