Histology Ch 14 466-474
Thymus
-Thymus is a bilobed organ in superior mediastinum anterior to heart; develops from 3rd and 4th
branchial pouch. Developmentally, epithelium invaginates and thymus grows caudally as a
tubular projection of endodermal epithelium into mediastinum; tip proliferates and becomes
disconnected from branchial epithelium
-Multipotential lymphoid stem cells (CFU-Ls) – from bone marrow become immunocompetent
T cells that invade epithelial rudiment of thymus and occupy spaces between epithelial cells, so
thymus develops as a lymphoepithelial organ
-thymus fully formed and functional at birth and persists until puberty, when T cell
differentiation and proliferation are reduced and thymus replaced with adipose tissue, but can
be restimulated under conditions that demand rapid T cell proliferation
General Architecture of Thymus – connective tissue surrounds thymus and divides it into
lobules; connective tissue capsule from which trabeculae extend into parenchyma of organ
containing blood vessels, EFFERENT lymphatic vessels, and nerves
-connective tissue of thymus has collagen fibers, fibroblasts, granulocytes, lymphocytes, mast
cells, adipose cells, and macrophages
-trabeculae establish thymic lobules, which are not true lobules, but rather cortical caps over
portions of highly convoluted continuous inner medullary tissue
-Thymic parenchyma contains developing T cells in an extensive meshwork formed by
epithelioreticular cells
-the thymic cortex is basophilic and contains developing T cells (thymocytes) with intensely
stained nuclei, and occupy spaces within meshwork of epithelioreticular cells, whichprovide
framework for developing T cells and correspond to reticular cells and their fibers, but also have
intercellular junctions and intermediate filaments (epithelial nature).
-macrophages are also inside cortical cells
-T cells arise from CFU-L cells in bone marrow
-Six types of epithelioreticular cells: 3 in cortex (I-III) and 3 in medulla (IV – VI)
1. Type I Epithelioreticular cells - boundary of cortex and CT capsule and between cortical
parenchyma and trabeculae, and surround blood vessels; function to separate
parenchyma from CT
2. Type II Epithelioreticular cells – within cortex, contain, macula adherens (desmosomes)
that join long, cytoplasmic processes of adjacent cells; contain intermediate filaments;
function to COMPARTMENTALIZE CORTEX INTO AREAS for T CELL DEVELOPMENT. Type
II cells contain MHCI and MHCII cells for thymic cell education
3. Type III Epithelioreticular cells – boundary of cortex and medulla and create functional
barrier between cortex and medulla and possess MHCI and II molecules
4. Macrophages – reside in cortex, responsible for phagocytosis of T cells that fail
requirements; 98% of T cells undergo apoptosis and are phagocytized, called PAS cells
-crosstalk – phenomenon where T cells at different stages of differentiation control
microarchitecture of thymic epithelioreticular cells
-thymic or Hassall’s corpuscles are DISTINGUISHING FEATURE OF MEDULLA**
-Thymic medulla – inner portion of parenchyma, contains epithelioreticular cells and loosely
packed T cells; stains less intensely than cortex because it contains LARGE lymphocytes which
have pale-staining nuclei
-thymic medulla contains 3 types of epithelioreticular cells:
1. Type IV Epithelioreticular cells – between cortex/medulla close to type III, and possess
sheetlike processes with occluding junctions between cells to help create barrier at
corticomedullary junction
2. Type V Epithelioreticular cells – located all over medulla, like type II cells are connected
by desmosomes to provide medullary framework and compartmentalize T cells
3. Type VI Epithelioreticular cells – form MOST CHARACTERISTIC FEATURE OF MEDULLA,
the thymic (Hassall’s) corpuscles, which are isolated masses of closely packed,
concentrically arranged TYPE VI epithelioreticular cells with flattened nuclei
a. These corpuscles reveal keratohyalin granules, intermediate filaments, and lipid
droplets; cells joined by desmosomes
b. Center of corpuscle may show keratinization
c. Corpuscles are unique, may be antigenically distinct, and functionally different
(produce interleukins)
-blood vessels pass from trabeculae to enter parenchyma of thymus; vessels enter medulla from
deeper parts of trabeculae and carry sheath of CT with them
Blood-Thymus Barrier and T-Cell education – blood thymus barrier protects developing
lymphocytes in thymus from antigen exposure
-T cells reaching cortex are prevented from antigen contact by blood-thymus barrier, composed
of, from the LUMEN of BLOOD VESSELS  Outward
1. Endothelium – lining capillary wall is continuous with occluding junctions (impermeable)
and is major structural component of parenchyma
a. Basal lamina + pericytes are also part of capillary wall
2. Macrophages – in perivascular connective tissue may phagocytize antigenic molecules
that escape lumen into parenchyma
3. Type I epithelioreticular cells – with occluding junctions provide protection to T cells,
surround capillary wall in cortex
Thymus is the site of T-cell Education – in fetus, thymus is populated by multipotent lymphoid
stem cells from bone marrow destined to become T cells (Thymic cell education)
-process is characterized by expression and deletion of CD antigens
1. Double-negative stage (early stage of differentiation) – expression of CD2 and CD7 on T
cell surface; double negative meaning LACK of CD4 and CD8
2. Middle Stage – expression of CD1
3. Double-positive stage – T cells express TCR, CD3, CD4, and CD8; these cells are
presented with self- and foreign antigens by type II/III epithelioreticular cells
a. Positive Selection – if lymphocyte recognizes self-MHC molecule or foreign
antigen, they survive – otherwise they will die
b. Cells passing positive selection will migrate from cortex to medulla to undergo
another selection process in where cells recognizing self-antigen by self-MHC
are eliminated, called negative selection
c. Cells surviving negative selection become either cytotoxic CD8+ T cells by losing
CD4 or they become helper CD4+ T cells by losing CD8
d. This stage is called single-positive stage
Spleen – size of fist; largest lymph organ in upper quadrant of abdominal cavity; rich vasculature
-the spleen filters blood and reacts immunologically to blood-borne pathogens
-spleen has both morphologic and immunologic filtering functions; has both large numbers of
lymphocytes AND special vascular spaces or channels, a meshwork of reticular cells and fibers,
and a large number macrophages and dendritic cells allowing spleen to monitor blood
immunologically
-spleen is enclosed by capsule from which trabeculae extend into parenchyma
-trabeculae contain myofibroblasts producing CT fibers and can contract
-spleen holds large volumes of RBCs in reserve; contraction of capsule and trabeculae
helps discharge stored RBC into systemic circulation
-Hilum – medial surface of spleen, is site of splenic artery, veins, nerves, and lymph vessels
-lymph vessels originate in white pulp near trabeculaee and form a route for
lymphocytes leaving spleen
-spleen contains two regions white pulp and red pulp; white pulp is circular, surrounded by red
pulp
-white pulp – consists of thick accumulation of lymphocytes surrounding an artery, and is
basophilic on H&E stains
-splenic artery branches course through capsule/trabeculae and enter white pulp,
becoming the central artery when inside
-lymphocytes aggregate around central artery and constitute periarterial lymphatic
sheath (PALS), which conforms to a cylindrical configuration down artery, and may
resemble a lymphatic nodule
-presence of central artery distinguishes PALS from other lymph nodules
-nodules of PALS are B cell territory, wherase other lymphocytes of PALS are T cells surrounding
the nodules
-PALS may be considered thymus-dependent zone similar to deep cortex of lymph node
-nodules contain germinal centers which develop as B cells proliferate after activation (24 hours
after antigen exposure and may become enlarged
-enlarged nodules are called splenic nodules
Red Pulp contains large numbers of RBCs that it filters and degrades – red pulp consists of
splenic sinuses separated by splenic cords (consist of loose meshwork of reticular cells and
fibers that contain RBC, macrophages, lymphocytes, dendritic cells, plasma cells, and
granulocytes)
-splenic macrophages phagocytose damaged RBC; iron from RBC is used in formation of
new RBC, and splenic macrophages begin process of hemoglobin breakdown
Splenic or Venous Sinuses are Special Sinusoidal Vessels lined by Rod-Shaped Endothelial Cells
– Endothelial cells lining splenic sinuses are extremely long running parallel to vessel
-there are few contact points between adjacent cells, forming prominent intercellular spaces to
allow RBC to pass in and out of sinuses
-macrophages processes extend between endothelial cells into lumen of sinuses to monitor
blood for antigens
-sinuses do not have continuous basal lamina
-Strands of Basal Lamina – loop around outside of sinus like hoops at right angles to long axis of
endothelial cells
-no smooth muscle or pericytes are at walls of splenic sinus
Circulation within red pulp allows macrophages to screen antigens in blood – central artery
sends branches to white pulp and to sinuses at perimeter of white pulp which are called
marginal sinuses.
-Central artery continues to red pulp where it branches into several arterioles called penicillar
arterioles which continue as arterial capillaries
-some of the capillaries are surrounded by aggregations of macrophages, making them
called sheathed capillaries, which empty into reticular meshwork of splenic cords rather
than connecting to endothelium-lined splenic sinuses
-blood entering red pulp this way percolates through cords and is exposed to macrophages of
cords before returning to circulation by squeezing through walls of splenic sinus
-this is called open circulation and is the only route by which blood returns to venous
circulation in humans (closed circulation happens in rat and dog)
-open circulation exposes blood more efficiently to macrophages of red pulp
-blood from sinuses drains to tributaries of trabecular veins that converge into lager veins and
leaves spleen by splenic vein  hepatic portal vein
Spleen performs both immune and hemopoietic functions – spleen filters blood similar to
lymph nodes and lymph, functions in both immune and hemopoietic systems
-Immune systems include (all happen in white pulp):
-antigen presentation by dendritic cells/macrophages and immune initiation
-activation/proliferation of B and T cells
-production of antibodies against antigen present in circulating blood
-removal of macromolecule antigens from blood
-Hemopoietic Functions of spleen (in red pulp)
-remove and destroy senescent, damaged, abnormal RBC and platelets
-retrieval of Fe from RBC hemoglobin
-formation of RBC during early fetal life
-storage of RBC in some species
-role of red pulp is primarily blood filtration by removing particular material, macromolecular
antigens, and aged, abnormal RBC and platelets
-macrophages embedded in reticular meshwork of red pulp
-senescent, damaged, abnormal RBC are broken down by lysosomes of macrophages
and Fe of hemoglobin is retrieved and stored as ferritin or hemosiderin
-hemo portion is broken down to bilirubin  liver to form glucuronic acid and
secreted into bile
-Macrophages recognize senescent/abnormal blood cells in 2 ways:
1. Nonspecific mechanisms – morphologic and biochemical changes in aged
erythrocytes cause them to be more rigid and easily trapped in mesh of red pulp
2. Specific mechanisms – opsonization of cell membrane with anti-band 3 IgG
antibodies, which trigger Fc receptor-dependent phagocytosis of erythrocytes
-also, specific glycosylation of glycophorins in aging erythrocytes act as
recognition signal to trigger elimination
-spleen is NOT essential for human life, and can be removed surgically, after which RBC
destruction occurs in the bone marrow and liver