histology of the immune (lymphoid, lymphatic) system
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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. - PowerPoint PPT PresentationTRANSCRIPT
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