Histology: Immune System

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components of immune system

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1. cells
2. aggregated tissues
3. organs
-that defend body-

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migratory cells

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-free to move
- diapedesis through tissue
- recirculation through lymph or blood

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fixed cells

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form stromal matrix
- epithelial or mesenchymal

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lymphocyte

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-small, round cell with spherical nucleus and scant cytoplasm
- types differentiated based on fx and specific proteins expressed

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B cell origin and maturation

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-bone-marrow derived
- mammals matures in bone marrow
- avian: matures in bursa of fabricius
- 10% of lymphocytes

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basic B cell functions

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-synthesize immunoglobulins: proteins on cell surface or secreted into surrounding fluids
-can bind and recognize antigens
-principle cell in humoral immunityL protective effects trhough tissue fluids
-

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active B cell types

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divides into two cell types:
1. memory: survive up to years, memory for specific antigen
2. plasma: produce large quantities of immunoglobulins, very basophilic, in CT

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B cells as antigen presenters

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-process and display foreign substances in a manner that can be recognized by T lymphocytes
- antigen presentation depends on cell surface proteins called major histocompatibility complexes (MHCs) which are unique to both antigen and animal

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red cell series

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darker staining

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white cell series

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lighter staining
-relatively smaller nucleus

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stroma

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structural framework of organ

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parenchyma

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functional cells of an organ

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T cells origin, maturation

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-develop from immature precursors that leave bone marrow, travel to the thymus and mature there
-75% of blood lymphocytes

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T cell receptors

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-T cells do not express immunoglobulins
- express surface (transmembrane) proteins called T cell receptors
- proteins are not excreted

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T cells: cell-mediated acquired immunity

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only recognize foreign proteins presented by antigen-presenting cells

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T cells: CD2 and CD3

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transmembrane protein complexes
-early in development
- can be used to ID cells

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T cells: CD8

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- T cell subpopulation
- cytotoxic (supressor) cell
- kills cell with foreign macromolecules on surface
- role in viral defense
-kills by perforins or apoptosis

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T cells: CD4

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-T cell subpopulation
- helper cell
- promotes proliferation, maturation and immunological function of other cells types
- decreased number in FIV cats

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differentiation of naive B or T cells

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- leaves bone marrow or thymus: activated and divide several times
1. memory cells: revert to resting, wait until next exposure to antigen
2. effector cells: carry out defense activities

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NK cells origin and maturation

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- derived from bone marrow
-don't go to thymus for further development
- 10-15% of blood lymphocytes
-not usually found in nodes or lymph

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NK cell functions

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-lack Ag receptors of B and T cells
- defined initially by their ability to lyse virally infected cells without prior immunization
- lyse certain tumor cell lines, but little evidence the NK cells normally protect against tumors

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neutrophil appearance

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-multilobed nucleus
- mature: 4-5, mature, haven't been recruited, indicates good health
-new cell: kidney-shaped nucleus, response to stimulus
- storage granules containing bacteriocidal agents and lysosomal enzymes

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neutrophil origin

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produced in bone marrow
-circulating in the blood

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neutrophil function

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phagocytic cell
-acute inflammation: first waves arrives as early as 30min after insult to tissue, dies afterwards
- when reaching inflammed tissue: 1. adhere to activated endothelium of postcapillary venules
2. emigrate through the vessel wall 3. invade the tissue

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macrophage origin and development

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-produced in bone marrow
- from monocyte cell line: briefly circulate as a monocyte and then enter tissue to become a macrophage
eg fixed sinusoidal in liver: phagocytise RBCs

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macrophage appearance

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-indented nucleus
-vacuoles abundant in cytoplasm
- fixed or wandering
- larger than neutrophil

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macrophage function

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-phagocytosis: degrade and sequester foreign material
- activate when it encounters a certain highly inflammatory mediators, becoming highly phagocytic
-acts as an antigen-presenting cell
-secretes cytokines

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macrophages indicate

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-live longer than neutophils
-indicative of chronic infections: 7-10 days

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stromal cells

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from framework of lymphoid organs

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reticular cells

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-stromal cells of lymphoid
- mesenchymal origin
- synthesize reticular fibers which form a reticulum in lymphatic organs except thymus and cloacal bursa

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epithelial reticular cells

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-stromal cells of lymphoid
- epithelial origin: endoderm
- thymus and cloacal bursa have stellate epithelial reticular cells which form the stroma
- DO NOT produce reticular fibers

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dendritic cells

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-stellate-shaped cells in nearly all tissues
- capture and present antigens to lymphocytes and activate T cells
- most arise in bone marrow (except FDC)

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follicular dendritic cells

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-in B cell areas of lymphatic tissue
- bind Ag and present to B cells
- lack MHC-II
- doesn't arise in bone marrow

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interdigitating dendritic cells

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-in lymph nodes, thymic medulla, spleen
- have MHC-II on surface
- present Ag to T (helper) lymphocytes

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intraepidermal macrophage (Langerhans cell)

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- dendritic cells
- found in deep layers of skin
- trap immune complexes and present antigen to lymphocytes

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veiled cells

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-dendritic cells
- in lymph and blood
-characterisitic: lots of folds
- may be transition cell from IDC and Langerhans cell

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diffuse lymphatic tissue

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- small lymphocytes and macrophages in a stroma of dendritic cells and CT
- scattered throughout loose CT of the: 1. gut
2. respiratory tract
3. UG system
4. skin

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primary lymphatic nodule

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- aggregates of lymphoid cells with a stromal network of CT
- lack germinal centers

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secondary lymphatic nodule general

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- have germinal centers comprised of B cells
- large lymphoblasts and tingible body macrophages present: TBM has fragments of phagocytized lymphocytes in cytoplasm
- intense cellular activity in germinal center

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germinal centers

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lighter staining in the center of a nodule
-characteristic of secondary nodule
- comprised of B cells

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zones of secondary lymphatic nodule

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- intense cellular activity in germinal center:
1. mitosis: dark zone
2. euchromatic nuclei: in light zone,
basal and apical
3. mantle: forms cap over nodule
- cells migrate and develop: dark--> light: basal then apical --> mantle

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primary lymphatic organs

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-provide microenvironments necessary for lyphopoeisis: dev lymph cells
- stem cells are isolated away from antigens
- cells that leave are naive: not exposed to antigens
- cells which are autoreactive are eliminated by apoptosis

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bone marrow

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-primary lymphatic organ
- source of stem cells
- site of B cell differentiation

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nodule in ileum (Peyer's patch)

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-aggregated lymphatic nodules
- young sheep, cattle, carnivores
- single, large aggregate of lymphatic tissue in distal ileum
- expansion of early B cell populations
- not strictly primary: isolated from circulating anitgens but B cells that arrive are already committed
-involutes with age

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nodules in jejunum

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-aggregated lymphatic nodules
- persist throughout life
-primary lymphatic organs

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cloacal bursa / bursa of fabricius

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-primary lymphatic organs: dorsal cloacal wall
- involutes with age
- site of B cell differentiation: functional equivalent of mammalian bone marrow
- comprised of lymphoid nodules with a stroma of epithelial reticular cells beneath a simple columnar or pseudostratified epithelium
- high ability to transfer antigens to nodule

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thymus general

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-mammals and birds
- lobulated primary lymphatic organ
-cortex and medulla in each lobule which distinguishes it

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epithelial origin of thymus

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-arises from endoderm lining the 3rd pharyngeal pouch in embryo
-epithelium spreads to form an epithelium reticulum

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mesenchymal origin of thymus

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- lymphocytic stem cells migrate from the mesenchyme of bone marrow into the space between the reticulum
-stem cells (thymocytes) develop into T cells which migrate to a secondary lymphoid organs

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cortex of thymus

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-darker staining than medulla
- lymphoblasts and lymphocytes fill the spaces
- tingible body macrophages remove dead lymphocytes
- about 98% T cells die in cortex
- surviving cells go to the medulla and then to secondary organs

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epithelial reticular cells of thymus

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-large, pale nuclei and branching cytoplasmic process form a stromal network
- line the periphery of lobules
-surround blood vessels
- form occluding junctions to create a network
- completely isolate thymic cortex and shelter developing T cells from circulating antigens
-produce thymic hormones

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appearance of lymphoblasts

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active
-light staining

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appearance of lymphocytes

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resting
-dark staining

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medulla of thymus

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1. epithelial reticular cells:
- tend to be larger
- may cluster to form thymic (Hassall's) corpuscles which are calcified or degenerated central cells surrounded by flat, keratinized outer cells
2. interdigitating dendritic cells

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blood supply to thymus

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-blood vessels enter at the corticomedullary junction and course to form a capillary network in the cortex
-capillaries then drain into post-capillary venules
- T cells enter blood through the post-capillary venule wall and migrate to diffuse or enter secondary lymphatic tissues and organs

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blood-thymus barrier

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-continuous capillary surrounded by a sheath of epithelial reticular cell processes
-vessel wall plus sheath form the blood-thymus barrier which decreases antigen access in the cortex

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thymic involution

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-thymus involutes after sexual maturity
- lymphocytes decrease and adipose tissue infiltrates

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secondary lymphatic organs

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-site of maturation of lymphocytes:
where exposed to foreign substances

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Mucosa-associated lymphatic tissue (MALT)

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- secondary lymphatic organs
- associated with the mucosa of the respiratory, digestive, and urogenital tracts

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tonsils

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-MALT, secondary lymphatic organs
- epithelium covers nodules surrounded by diffuse lymphatic tissue
- surface may be smooth or invaginated in fossulae that continue as crypts
- no afferent lymph vessels
- surrounded by capsule which makes enucleation easier

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tonsils of oropharynx and nasopharynx

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1. oropharynx: stratified squamous epithelium
2. nasopharynx: respiratory epithelium
- leukocytes that reach the surface of the epithelium form salivary corpuscles

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goblets cells and immune areas

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few goblet cells in immune areas

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bronchus-associated lymphatic tissue (BALT)

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- secondary lymphatic organ
- clusters of B and T cells in the wall of bronchi and bronchioles
- epithelium contains M cells

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gut-associated lymphatic tissue

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-aggregated lymphatic nodules (Peyer's patch) in young
- solitary and aggregated lymphatic nodules in older animals

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components of aggregated lymphatic nodules of BALT

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1. submucosal lymphatic zone
2. corona (mantle): zone of small lymphocytes that caps the nodule
3. internodular region: T cells in post-capillary venules
4. dome: elevated region over nodule
5. nodule associated epithelium: M cells

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M cells of nodule associated epithelium

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=microfolds
- capture antigen and transfer it to macrophages without processing
- no goblet cells in this region of epithelium
- of nodule associated epithelium of GALT

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lymph node

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-secondary lymphatic organs
- filter antigens from circulating lymph
- nodes have both afferent and efferent lymph vessels

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capsule of cortex (of lymph node)

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-CT containing afferent lymphatics

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subcapsular sinus of cortex (of lymph node)

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-lined by endothelial-like reticular cells -spanned by stellate reticular cells
- lymph percolates through sinus

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paracortex of cortex (lymph node)

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-surrounds lymphatic nodules
-T lymphocytes are in deep region

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cortical sinuses of paracortex of cortex (lymph node)

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- extend from subcapsular sinus

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cortical trabecular of paracortex of cortex (lymph node)

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-CT from capsule which extends to cortex
- stroma is reticular fibers which contain lymphocytes, macrophages and plasma cells

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lymphatic nodules of cortex (of lymph node)

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1. germinal centers:
-present in active nodules
- light-staining
a. dark zone: B cell proliferation
b. light zone: where B cells are exposed to antigen by follicular dendritic cells
2. corona (mantle): dark peripheral region where small lymphocytes migrate away from the nodule

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medulla of lymph node

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1. medullary cords: cords of plasma cells, lymphocytes and microphages
2. medullary sinuses: extension of cortical sinuses, very light area

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lymph flow through a node

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1. afferent lymphatics empty lymph into the subcapsular sinus
2. lymph then percolates into the cortical sinuses followed by medullary sinuses
3. exits through the efferent lymphatic at the hillus

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blood supply to lymph node

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1. major blood vessel supply enters and exits at the hillus
2. vessels supply the medullary cords and continue into the cortex to supply the nodules
3. internodular branches form capillary arcades below the subcapsular sinus and then continue on to form postcapillary venules (HEV's)

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HEV's (high endothelial vessels)

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= postcapillary venules
- allow blood access to lymph: site where lymphocytes exit and enter the blood
- lined by cuboidal epithelium

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recirculation of lymphocytes

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1. lymphocytes leave the node via efferent lymphatics
2. lymph empties into the blood
3. when lymphocytes in the blood reach HEV's they exit back into the tissue (lymph node)

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species variation in lymph nodes

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-nodules are located deep in the porcine node rather than at the periphery

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spleen

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-secondary lymphatic organ
-hemopoeisis: formation of blood cells, in younger animals
- filters blood
- stores erythrocytes and platelets
- site of lymphopoesis
-removes spent erythrocytes

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pentobarbitol and spleen

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relaxes smooth muscle in the capsule, allowing the spleen to expand

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capsule and trabeculae of spleen

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-CT and smooth m.

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white pulp of spleen

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-dark staining
-lymphatic nodules and diffuse lymphatic tissue distributed throughout the spleen:
1. nodules are B cell zones
2. diffuse are PALS
- reticular cells and fibers form the stroma of the white pulp

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PALS of white pulp (of spleen)

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=periarterial lymphatic sheaths
-located along the artery of the white pulp
- T cells and concentrated in the t. media or the artery
- T cells, B cells, macrophages in the periphery

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red pulp of spleen

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-most of the splenic parenchyma
1. sinuses
2. cords

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splenic sinuses of red pulp

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-venules in most domestic animals
- wide vascular channels lined by longitudinally oriented endothelial cells with fenestrated basal lamina
- gaps in the sinus (or venule) wall allow cells to enter circulation from the splenic cords

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splenic cords of red pulp

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-cords between cells of the sinus
- reticular cells, erythrocytes, macrophages, lymphocytes, plasma cells embedded in mesh of reticular fibers

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marginal zone of spleen

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- between white and red pulps
- marginal sinus
-sheathed capillaries
- elements in the blood contact the macrophages in the marginal zone, facilitating phagocytosis and initiating the immune response
- macrophages shuttle antigens to the PALS where lymphocytes are located

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marginal sinus of spleen

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capillaries leave the PALS and pass through a rim of macrophages, reticular and B cells and empty into marginal sinus

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sheathed capillaries of marginal zone (of spleen)

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some blood vessels pass through the marginal zone and terminate as sheathed capillaries (ellipsoida) in the red pulp
-sheath of macrophages and reticular cells

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blood vessels of the spleen

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splenic a. > trabecular a. > artery of the white pulp > (end in marginal sinus or continue as penicillar a.) > pulp arteriole > sheathed capillary (ellipsoid) > terminal capillary
-drain through veins of the pulp > splenic v. > portal v.

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closed theory of splenic blood vessels

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terminal capillary expands and opens directly into splenic sinus (venule)

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open theory of splenic blood vessels

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-terminal capillaries open into spaces between reticular cells of the red pulp
-blood then enters the venous sinuses through slits in the wall of the sinus

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both theory of splenic blood vessels

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1. when spleen distended, sinuses are pulled apart and blood leaks from the terminal capillaries in open fashion
2. when contracted, vessels are pushed together and the circulation is close

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lymphatics of spleen

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- spleen has no afferent lymph vessels
- efferent vessels originate in the white pulp

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hemal node

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-secondary lymphatic organ
- described in ruminants: sublumbar area along vena cava and aorta
- develop from lymph node primordia that lose their lymph vessels
- receive their cells and antigens from the blood
- exact function unclear: may respond to blood-bourne antigens
- comprised of blood-filled sinuses with diffuse lymphatic tissue

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origin of lymph vessels

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originate as an anastomosing system of capillaries in the CT which connects to larger lymph vessels that pass through lymph nodes

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endothelium of lymph vessels

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-histochemical markers may help distinguish blood and lymph capillaries
- gaps are often present between cells and may be transient
- basal lamina is discontinuous or absent in lymph capillaries

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lymph vessel structure

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-fine ECM anchoring filaments attach the endothelium to adjacent collagen or elastic fibers: keeps lymphatic patent
- valves are present in capillaries (sometimes) and larger vessels (always)
- wall of a larger lymph vessels thicker with smooth m and more collagen
- thinner walls that veins`