Histology of the immune (lymphoid, lymphatic) system

• Jeanne Adiwinata Pawitan

• Dept. of Histology

• FMUI

Immune system

• Cells of the immune system

• Bone marrow (myeloid tissue)

• Diffuse lymphoid system° Diffuse lymphoid tissue° Lymph (lymphoid) nodules

• Lymphoid organs - capsule

Immune system – defense mechanism

• Function: protection >< foreign elements° Foreign macromolecules° Invasive microorganisms• Viruses

• Bacteria

• Others

° Transformed cells

Defence mechanism (Martini)

• Non specific defenses° Physical barriers° Phagocytes (M, neutro, eosinophils, monocytes)° Immunological surveillance: NK cells° Interferons, complement system° Inflammatory responses, fever

• Specific defenses – specific immunity –specific immune response° Innate (human >< animal disease, except AIDS)° Acquired

Immune response

• Specific recognition system (specific immune system)° Recognize self >< non self° Component • Cellular (lymphocytes B, T)• Soluble (Ig)

• Nonspecific (innate) effector system (non specific immune system)° Amplifies – function – specific system

Nonspecific immune system• Soluble component° Complement proteins (cytokines): lymphokines-

monokines: interleukines (ILs), interferons (IFNs), tumor necrosis factors (TNFs), transforming growth factors (TGFs), hematopoietic colony-stimulating factors (CSFs)

• Cellular component – phagocytes:° Blood: neutrophils, eosinophils, monocytes

° Tissue: macrophages (alveolar macrophages, Kupffer’s cells, synovial cells – joint cavities, perivascular microglial cells – CNS)

Bone marrow (red) – myeloid tissue

• Location: ° central (marrow, medullary) cavity – long bones

° Interstices (trabeculae) – spongy/cancelous bones

• Soft, gelatinous, highly vascular – cellular tissue• Function: hemopoiesis – 5th month prenatal• LM: ° vascular compartment (A., V., sinusoids)

° Intervening spaces • hemopoietic compartments – meshwork - islands of

hemopoietic cells

• Adventitial reticular cells, reticular fibers

Bone marrow cells• Hemopoietic cells° Blood cells – various stages° Macrophages – destroyed• Nuclei – erythrocytes precursors• Malformed cells• Excess cytoplasm

• Adventitial reticular cells ° By age 20 – adult: cytoplasm - accumulate fat • ≈ adipose cells – large – reduce hemopoietic

compartment yellow marrow

Diffuse lymphoid system• Non-encapsulated• Location: ° Lymphoid organs° Mucosa (lamina propria) – mucosa associated

lymphoid tissue (MALT)• Digestive system (Gut ALT): Peyer’s patches• Respiratory system (Bronchus ALT)• Urinary system

• Occur as° Diffuse lymphoid tissue = localized lymphocyte

infiltration° Lymphoid nodules (lymphonodulus)

Diffuse lymphoid tissue

• Consists of° Stroma • Reticular fibers – silver impregnation

• Reticular cells of mesenchymal origin – some are phagocytic ≈ fixed macrophages

° Lymphocytes ° Free macrophages° Plasma cells

Reticular cells

• Shape: elongate – stellate• Nucleus: ovoid – euchromatic• Cytoplasm:° Scanty° Acidophilic ° Contains• RER – few• Golgi complex – moderate-well developed• Fine filaments – bundles – at periphery

Lymph (lymphoid, lymphatic) nodule, lymphonodulus – lymphoid follicles

• =circumscribed-spherical/ovoid-closely packed-lymphocytes

• In diffuse lymphoid tissue• Location:° Lymph node –cortex° Spleen – white pulp° Tonsils ° Lamina propria (MALT): Peyer’s patches, etc.

Lymph nodule• = primary nodule• Consists of° Germinal center = secondary nodule = ovoid area –

contains: larger, pale-staining cells• Less densely populated pole – light region/zone• Densely populated pole – dark region/zone

° ‘cap’ = corona, cortex, mantle – small lymphocytes –densely packed – facing less dense pole - directed toward• Marginal sinus• Red pulp• Epithelium (MALT)

Germinal center – diff. B limphocytes- IgG

• Dendritic (stellate) cells, dendritic macrophages ° Silver method° Cellular framework° Radiating processes – desmosomes° Non phagocytic, bind Ag – Ag presenting – activate T

lymphocytes

• Flattened reticular cells – desmosomes: outer boundary• Lymphoblast – actively proliferating• Lymphocytes: large, medium, small - esp.dark region• Transition to plasma cells• Plasma cells (scarce, except in tonsils)• Macrophages – ↓toward dark region

Gut-associated lymphoid tissue• Isolated lymphoid follicles• Peyer’s patches – aggregates – ileum° Lymphoid follicles

• B cells• T cells – looser – surrounding B Cells• Numerous APC – surrounding B cells

° Simple columnar epithelium M (microfold) cells – capture Ag present their epitopes to lymphocytes

° Afferent lymph vessels (-), ° Efferent lymph drainage (+)° Received small arterioles capillary bed high

endothelial lined venules (HEVs)° Lymphocytes entering Peyer’s patches have homing

receptors – specific for HEVs of GALT

Bronchus-associated lymphoid tissue

• ≈ Peyer’s patches – walls – bronchus – esp. bronchi-bronchiole bifurcate

• Epithelial cover: pseudostratified ciliated columnar epithelium with goblet cells M cells

• Afferent lymph vessels (-)• Efferent lymph drainage (+)• Rich vascular supply HEVs° Possible systemic and localized role in immune

response° Lymphocytes entering BALT have homing receptors

for HEVs of BALT

• Cells: mostly B cells, also APC, T cells

Lymphoid organs

• Thymus (primary lymphoid organ)

• Lymph nodes (lymphonodus)

• Spleen (lien)

• Tonsils (tonsila)

Thymus

• Location: superior mediatinum – anterior of great vessels (aorta)

• After puberty – involution (atrophy) → adult – adipose cells

• 2 lobes

• Encapsulated – dense-irregular-collagenous connective tissue septa (trabecula) – lobes incomplete lobules

Thymus - lobules• Cortex – darker° Epithelial reticular cells – endodermally

derived – type I, II, III° T lymphocytes (thymocytes):

immunologically incompetent competent° Macrophages

• Medulla – confluent – lighter° Epithelial reticular cells – endothelially

derived- type IV, V, VI° Lymphocytes – less than in cortex

Thymus – vascular supply

• Small arteries – capsule – trabecula corticomedullary junction – capillary beds cortex - continuous capillary ° Thick basal lamina° Sheath – epithelial reticular cells type I

(occluding junction) – blood-thymus barrier

medulla – small venules – veins - out

Thymus – histophysiology• Cortex: ° T cells proliferate – surface markers – maturation

capable to recognize• Self MHC molecules incapable - detroyed• Self epitopes

° Epithelial reticular cells type I, II • Test the ability of T cells: have

MHC molecules Epitopes

• Produce hormones maturation of T cells Thymosin Thymopoietin Thymulin Thymic humoral factor

Maturation of T cells

• Role of extrathymic hormones ° Suprarenal, gonads – adrenocorticosteroids

T cell number in thymic cortex↓° Thyroid – thyroxin stimulate epithelial

reticular cells - thymulin↑° Pituitary – somatotropin promotes T cell

development in thymic cortex

Lymph node

• Location: interposed in the path of lymph vessels-esp.° Neck, axila, groin

° Along major vessel

° body cavities

• Functions:° Filter – remove

• Bacteria

• Foreign substances

Lymph node

• Small, soft, Ø < 3 cm

• Capsule – fibrous connective tissue (thickened at hilum) - trabeculae - adipose tissue

• Convex: afferent lymph vessels – valves

• Concave = hilum: A., V., efferent lymph vessels – valves ← medulla

Lymph node - sinuses

Sinuses: network – stellate reticular cells – macrophages – endothelial-like simple squamous epithelium – migratory lymphoid cells

Course:Afferent lymphatic vessels• Subcapsular sinus• Cortical (paratrabecular) sinuses• Medullary sinusesEfferent lymphatic vessels

Lymph node

• Histologically:° Cortex – antigen-presenting follicular

dendritic cells• Primary lymphoid nodules (virgin B & memory

B cells)• Secondary nodules (with germinal centers) –

antigenic challenge B memory & plasma cell

° Paracortex – Thymus dependent zone° Medulla

Lymph node -paracortex• Cells ° Mostly T cells° APC comes (from outside) – presents epitope-MHC

II complex to T helper Th – is activated –proliferates width of paracortex ↑

° Activated Th medullary sinuses out to area of antigenic activity

• Postcapillary venules = high endothelial venules (HEVs) - cuboidal° endothelial cells - signaling molecules° Rolling lymphocytes – selectins >< signaling

molecules firmly bound – diapedesis – out to lymph node parenchyma

Lymph node - medulla

• Trabeculae – from hilum

• Medullary cords° Network – reticular fiber – reticular cells° Cells • Lymphocytes – migrating from cortex

medullary sinuses

• Plasma cells

• Macrophages

Lymph node - vascularization

• Artery (hilum) trabeculae medulla medullary cords ° Capillary beds in medulla° Cortex – cortical capillary beds

postcapillary venules (paracortex) vein - hilum

Lymph node – histophysiology

• Lymph - foreign particulate matter lymph node – macrophages-phagocytosis = filter

• Site of antigen recognition° APC – antigen (from outside) lymph node

– lymphocytes presentation of epitope-MHC complex

° Ag – trapped by follicular dendritic cells recognize by lymphocytes

Lymph node – histophysiology

• B lymphocytes – recognize Ag activated primary lymphoid nodule proliferates –diff B memory, plasma cells - secondary lymphoid nodule ° B memory (some)– stay in cortex

° B memory, plasma cells leave cortex medullary cords • Plasma cells (10%)– medulla - Ab medullary sinuses

• Plasma cells medullary sinuses bone marrow – Ab

• B memory out to secondary lymphoid organs 2nd exposure - prompt and potent secondary response

Spleen (lien)

• Largest lymphoid organ• Upper left quadrant – abdominal cavity • Intraperitoneal – visceral peritoneum• Function:° Proliferation B, T cells° Ab formation – blood-borne Ag inactivation° Elimination of Ag, bacteria, particles, etc.° Filtering blood – destroying old erythrocytes° Hemopoietic (fetal) – adult – when needed

Spleen (lien)

• Convex surface

• Concave surface – hilum – capsule-thickened° Arteries – nerve fibers (in)° Veins – lymph vessels (out)

• Dense – irregular connective tissue – capsule - occasional smooth muscle cells – trabeculae into the organ

Spleen (lien)

• Histology ° Network – reticular fibers – reticular cells –

attached to capsule trabeculae – blood vessels

° Fresh - cut - parenchyma• Grey area = white pulp

• (Marginal zone – 100 μm wide – between white – red pulp)

• Surrounding red area = red pulp (splenic cords of Billroth)

Spleen (lien) – blood supply

• Splenic artery - hilum branching trabecular arteries ( 0.2mm) central arteries – periarterial lymphatic sheath (PALS) ° Radiating - slender blood vessels red pulp (recur) -

marginal sinuses – marginal zone

° branching penicillar arteries – red pulp: • Pulp arteriole

• Sheated arteriole – Schweigger-Seidel sheath – macrophages)

• Terminal arterial capillaries – splenic sinuses

• Veins of the pulp splenic vein portal vein

Closed circulation – open circ.

• Closed circulation° Endothelial lining: terminal arterial

capillaries –continuous - sinuses

• Open circulation° Terminal arterial capillaries – red pulp -

sinuses

• Combination of both

Spleen (lien) – white pulp

• Central arteriole

• PALS: ° T lymphocytes° Frequently: lymphoid nodules (B cells) –

germinal center = antigenic challenge central arteriole - periphery

Spleen (lien) – marginal zone

• Cells ° Plasma cells

° T, B lymphocytes

° Macrophages

° Interdigitating dendritic cells (antigen presenting cells, APC)

• Marginal sinuses (vascular channels: inter-endothelial spaces 2-3 μm) – esp. surrounding lymphoid nodules particulate matter – free access to parenchyma

Spleen (lien) – marginal zone-events

• APC – search for Ag in blood• Macrophages – attack microorganism in

blood• Circulating B, T lymphocytes in blood

stream – enter the white pulp• Lymphocytes – contact with interdigitating

dendritic cells – if the epitope-MHC complex is recognized immune respons in white pulp

Spleen (lien) – red pulp sponge° Spaces = splenic (venous) sinuses (sinusoids)

• Endothelial lining – fusiform staves of a barrel

• Between endothelial cells - spaces - 2-3 m

• Surrounded by reticular fibers (continuous with splenic cords) – thin strands ┴ longitudinal axis

• Have a discontinuous basal lamina

° Sponge material = splenic cords of Billroth• Reticular fibers (collagen III) – loose network – interstices

permeated by extravasated blood

• Stellate reticular cells – isolate coll III from blood >< platelet reaction to coll >< coagulation

• Macrophages particularly numerous near sinusoids

Spleen –histophysiology

• Macrophages ° Marginal sinuses – macrophage rich° Periphery of splenic sinuses Phagocytosis

Ag, bacteria, particulate matter, etc Old erythrocytes

Less fkexible (old, malaria) –cannot penetrate spaces between endothelium

Surface coat: sialic acid residue (-) galactose moieties exposed – induced phagocytosis

Spleen –histophysiology

• Lymphocytes -Ag challenge white pulp ° B memory cells, plasma cells – lymphoid nodules° T cells (various subcategories) – PALS

marginal sinuses ° Site of Ag challenge ° Circulating pool of lymphocytes° Plasma cells• Some stay in marginal zone Ab marginal sinuses

• Most bone marrow – Ab bone marrow sinuses

Tonsils: palatine, pharyngeal, lingual

• Incompletely encapsulated• Aggregates of lymphoid nodules• Guard the entrance of oral (oro)

pharynx• Exposed to ° Airborne Ag° Ingested Ag

• Reaction to Ag° Forming lymphocytes° Mounting immune response

Palatine tonsils• Location° Boundary of oral cavity-oral pharynx° Between palatoglossal –palatopharyngeal folds

• Deep aspect - fibrous capsule• Surface – stratified squamous nonkeratinized

epithelium dips into crypts (10-12) - contain° Desquamated epithelial cells° Dead leucocytes, bacteria, other Ag substances° Food debris

• Inside – tonsilar parenchyma° Lymphoid nodules – many with germinal centers = B

cell formation

Pharyngeal tonsil• Location: roof of nasal pharynx• Capsule – incomplete, thinner vs palatine• Surface: pseudostratified ciliated

columnar epithelium – interspersed with patches of stratified squamous epithelium pleats = shallow longitudinal infoldings° Ducts of seromucous glands base pleats

• Inside = palatine tonsil• Inflamed adenoid

Lingual tonsil (several)

• Location: dorsal surface of posterior 1/3 of tongue

• Superficial – stratified squamous nonkeratinized epithelium – single cript ° Ducts of seromucous minor salivary glands

base of crypt

• Capsule – flimsy• Inside = palatine tonsil