Transcript imun-inter03 - Website Staff UI

Histology of the immune
(lymphoid, lymphatic) system
• Jeanne Adiwinata Pawitan
• Dept. of Histology
• FMUI
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Immune system
• Cells of the immune system
• Bone marrow (myeloid tissue)
• Diffuse lymphoid system
° Diffuse lymphoid tissue
° Lymph (lymphoid) nodules
• Lymphoid organs - capsule
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Immune system – defense mechanism
• Function: protection >< foreign elements
° Foreign macromolecules
° Invasive microorganisms
• Viruses
• Bacteria
• Others
° Transformed cells
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Defence mechanism (Martini)
• Non specific defenses
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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
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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
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Nonspecific immune system
• Soluble component
° Complement proteins (cytokines): lymphokinesmonokines: 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)
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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
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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
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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)
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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
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Reticular cells
• Shape: elongate – stellate
• Nucleus: ovoid – euchromatic
• Cytoplasm:
° Scanty
° Acidophilic
° Contains
• RER – few
• Golgi complex – moderate-well developed
• Fine filaments – bundles – at periphery
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Lymph (lymphoid, lymphatic) nodule,
lymphonodulus – lymphoid follicles
• =circumscribed-spherical/ovoid-closely
packed-lymphocytes
• In diffuse lymphoid tissue
• Location:
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Lymph node –cortex
Spleen – white pulp
Tonsils
Lamina propria (MALT): Peyer’s patches, etc.
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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)
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Germinal center – diff. B limphocytes- IgG
• Dendritic (stellate) cells, dendritic macrophages
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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
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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
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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
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Lymphoid organs
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Thymus (primary lymphoid organ)
Lymph nodes (lymphonodus)
Spleen (lien)
Tonsils (tonsila)
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Thymus
• Location: superior mediatinum – anterior
of great vessels (aorta)
• After puberty – involution (atrophy) →
adult – adipose cells
• 2 lobes
• Encapsulated – dense-irregularcollagenous connective tissue septa
(trabecula) – lobes  incomplete lobules
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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
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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
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Thymus – histophysiology
• Cortex:
° T cells proliferate – surface markers – maturation
 capable to recognize
• Self MHC molecules
• Self epitopes
incapable - detroyed
° 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
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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
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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
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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
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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 sinuses
Efferent lymphatic vessels
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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
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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
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Lymph node - medulla
• Trabeculae – from hilum
• Medullary cords
° Network – reticular fiber – reticular cells
° Cells
• Lymphocytes – migrating from cortex 
medullary sinuses
• Plasma cells
• Macrophages
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Lymph node - vascularization
• Artery (hilum)  trabeculae  medulla
 medullary cords 
° Capillary beds in medulla
° Cortex – cortical capillary beds 
postcapillary venules (paracortex)  vein hilum
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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 epitopeMHC complex
° Ag – trapped by follicular dendritic cells 
recognize by lymphocytes
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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
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Spleen (lien)
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Largest lymphoid organ
Upper left quadrant – abdominal cavity
Intraperitoneal – visceral peritoneum
Function:
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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
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Spleen (lien)
• Convex surface
• Concave surface – hilum – capsulethickened
° Arteries – nerve fibers (in)
° Veins – lymph vessels (out)
• Dense – irregular connective tissue –
capsule - occasional smooth muscle cells
– trabeculae  into the organ
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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)
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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
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Closed circulation – open circ.
• Closed circulation
° Endothelial lining: terminal arterial
capillaries –continuous - sinuses
• Open circulation
° Terminal arterial capillaries – red pulp sinuses
• Combination of both
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Spleen (lien) – white pulp
• Central arteriole
• PALS:
° T lymphocytes
° Frequently: lymphoid nodules (B cells) –
germinal center = antigenic challenge 
central arteriole - periphery
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Spleen (lien) – marginal zone
• Cells
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Plasma cells
T, B lymphocytes
Macrophages
Interdigitating dendritic cells (antigen presenting
cells, APC)
• Marginal sinuses (vascular channels: interendothelial spaces 2-3 μm) – esp. surrounding
lymphoid nodules  particulate matter – free
access to parenchyma
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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
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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
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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
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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
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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
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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
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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
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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
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