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LYMPHATIC SYSTEM.
I. What is the lymphoid system?
A. System for returning fluid to cardiovascular system.
B. Pathway for cells of the immune system to move through.
C. Comprises an organ/vascular system that protects the body’s internal
environment from the onslaught of foreign substances (i.e. bacteria, viruses,
etc.), and malignant growths.
D. 3 basic types of lymphoid tissue:
a. unencapsulated
b. incompletely encapsulated
c. completely encapsulated.
II. The lymphoid system consists of 2 major
components,
A. The lymph vascular network - two functions,
1. Acts to return extracellular fluids to blood
circulatory system.
2. Pathway for certain cells of the immune system
to move through, as well as re-enter the circulatory
system.
http://www.cs.stedwards.edu/~kswank/LymphSyst.html
B. Lymph organs and regions of diffuse lymphoid tissue
1. These organs/tissues are
a. lymph nodes
b. spleen
c. thymus
e. appendix
f. aggregations of lymph
nodules such as
Peyer’s patches
d. tonsils and adenoids
g. bone marrow
2. Serve at least two roles:
a. Filter cellular and particulate
debris
b. Sites of residence, activation and
proliferation of cells of the immune
system.
3. Diffuse lymphoid tissue - aggregations of
lymphocytes and other immune system cells usually not permanent. These may or may not be
nodular.
http://rex.nci.nih.gov/PATIENTS/INFO_TEACHER/bookshelf/NIH_immune/html/imm04.html
Classification based on encapsulation or lack thereof.
Encapsulated
Thymus
Spleen
Lymph nodes
Incompletely encapsulated
Tonsils, adenoids
Unencapsulated (sometimes called diffuse lymphoid tissue)
MALT - e.g. Peyer’s patches
Lymphoid tissue in appendix
Temporary aggregations of lymphocytes and other immune system
cells
III. Tissues of lymphoid organs consist of two major cell types,
A. Fixed cells
1. Reticular cells - connective tissue
cells that secrete fine matrix of reticular
fibers which these cells extend
cytoplasmic processes through and
around.
(reticulocyte is a bad term for these
cells since one stage of erythrocyte
maturation is also called a reticulocyte).
2. Follicular dendritic cells (FDCs) found in germinal centers of lymph
nodules - bind antigens for later
interaction with B-lymphocytes.
http://www.finchcms.edu/anatomy/histology/organology/lymphoid/images/ff614.jpg
B. Motile cells
1. Macrophages - antigen presenting cells
a. differentiate from monocytes that leave blood.
b. phagocytose particulates and bacteria
c. involved in initiation of humoral and cell-mediated immune
response
http://www.cellsalive.com/
monocyte
macrophage
Copyright Dennis Kunkel Microscopy
http://wsrv.clas.virginia.edu/~rjh9u/macro.html
http://www.pbrc.hawaii.edu/~kunkel/catalog/by_category/medical/page001/08974a.html
B. Motile cells
2. Various classes of T-lymphocytes
a. involved in initiation of humoral immune response
b. involved in cell mediated immune response
http://www.cellsalive.com/ctl.htm
3. B-lymphocytes, including plasma cells that secrete specific antibodies.
IV. Immune system functions of the lymphoid system
A. There are 3 major cell types involved in an immune response.
1. Antigen presenting cells (macrophages, dendritic cells) - process antigens
and present them to T- lymphocytes, this will result in the activation of
these cells which will then initiate humoral and cell-mediated immune
responses.
2. T-lymphocytes - once activated as above, these cells may be responsible for
cell-mediated immune responses or they may be involved in mediating the
activation of B-lymphocytes to produce antibodies in a humoral immune
response.
3. B- lymphocytes - responsible for antibody production - the humoral immune
response to an antigen that results in the secretion of antibodies by Blymphocytes that have become plasma cells.
B. What is an immune response:
1. Involves the recognition of foreign antigens by certain lymphatic cells
a. Antigen - a molecule that, in its make-up, has characteristics that will
cause the activation of certain cells in the immune system.
b. The portions of foreign molecules that immune system cells recognize
are called epitopes.
c. Epitopes are often parts of protein molecules that form part of the cell
membrane or wall of organisms that invade the bodies tissues.
2. An immune response results in changes in the gene activity and metabolism of
B- and/or T- lymphocytes that allows them to act in destroying the foreign
substance or organism
C. An immune response may be either humoral or cell-mediated.
1. Humoral immune response - secretion of antibodies that bind to a foreign antigen
by B-lymphocyte plasma cells.
a. Mediated by interaction between macrophage, T-lymphocyte and B-lymphocyte
b. Causes clonal proliferation of activated B-lymphocytes
c. ”Mature” (activated) B-lymphocytes are plasma cells or memory B-lymphocytes
Take a look at Figure
14-6 and corresponding
text on pp. 260-261 in
your text.
http://www.cellsalive.com/antibody.htm
* Plasma cells are short lived and secrete copious amounts of antibody that
are specific for a given antigen
** Antibodies act to identify foreign cells for attack by other
components of the immune system such as T-lymphocytes and
macrophages.
** Antibodies can also identify particulates and viruses for
phagocytosis and destruction by other leucocytes such as
neutrophils.
* B-lymphocyte memory cells remain dormant and will rapidly respond to
future encounters with the same antigen by rapid clonal proliferation and
differentiation into plasma cells that produce the needed antibody.
2. Cell-mediated immune response - antigen activates T-lymphocytes to produce
cytotoxic substances that cause the destruction of the antigen containing cell
a. Mediated by interaction between macrophage and T-cytotoxic (Tc)
lymphocytes
b. Causes clonal proliferation of Tc lymphocytes
c. ”Mature" (activated) Tc lymphocytes differentiate into either Tc
memory cells or Tc effector cells
* Tc effector cells - actively kill invading foreign cells
* Tc memory cells remain dormant and will rapidly respond to
future invasions by foreign cells expressing the same antigen
D. Without the activities of cells of the lymphoid system, your life on earth after birth
would be brief indeed.
V. There are 2 basic types of lymphoid tissue,
A. Non-nodular lymphoid tissue
1. Unencapsulated, sub-epithelial, aggregations of lymphocytes - diffuse
lymphoid tissue - can occur anywhere in body
2. Non-nodular aggregations of lymphocytes in lymphoid organs such as the
thymus, lymph nodes and spleen
B. Nodular lymphoid tissue - “spherically” arranged aggregations of
lymphocytes with a distinct cortex and medulla (germinal center) that are
called lymphatic nodules.
1. Nonencapsulated lymph nodules (diffuse lymphatic tissue)
2. Nodules in lymph nodes
3. Nodules in spleenic white pulp
* Some texts will identify the thymus as having nodular lymphatic tissue; however, this is
not really correct if nodules are as described above.
4. MALT (mucosa-associated lymphoid tissue) – nodular aggregations of lymphoid
tissue that are associated with the lining of the digestive tract, e.g., tonsils, appendix,
Peyer’s patches,. These tissues comprise the largest (admittedly diffuse) lymphoid
organ in the body and contain about 70% of the body’s immune cells.
****
VI. Structure and function of lymphoid organs
A. Lymphatic nodule
1. Consists of dense aggregation of lymphocytes that includes reticular cells,
macrophages and follicular dendritic cells.
2. Nodule consists of a cortex and the medullary germinal center.
3. No connective tissue capsule
directly surrounds individual
lymphatic nodules
4. Mainly found in the lamina propria
of the digestive tract, the respiratory
tract, and urinary passages. Also a
component of the lymph nodes,
spleen, tonsils and appendix.
4. Nodules may be classified as
“primary” or “secondary”
a. primary - germinal center not very
evident
b. secondary - germinal center very evident
http://www.finchcms.edu/anatomy/histology/organology/lymp
hoid/o_l_7.html
3. Lymphatic nodules - general composition:
a. Fixed cells - reticular cells in cortex and follicular dendritic cells in germinal center.
b. Free cells - B-lymphocytes, including immunoblasts (clonally dividing B-lymphocytes)
plasma cells, macrophages, a few eosinophils and mast cells.
* Mostly small lymphocytes
* Cortical cells are mostly Blymphocytes.
* Many of the medullary cells are
activated B-lymphocytes undergoing
clonal divisions - most of the resulting
cells will mature into plasma cells.
http://www.udel.edu/Biology/Wags/histopage/colorpage/cly/cly.htm
Peyer’s Patches - aggregations of lymph nodules in small intestinal wall of ileum.
http://www.finchcms.edu/anatomy/histology/organology/lymphoid/o_l_8.html
B. Lymph nodes
1. Oval or bean shaped bodies present along
the course of lymphatic vessels. Multiple lymph
vessels may connect to a lymph node.
2. Contains a stroma consisting of reticular
cells and fibers and large numbers of
lymphocytes, all surrounded by a connective
tissue capsule.
3. Reticular cells in the stroma provide a
physical support network for the lymphocytes.
Essentially an aggregation of lymphatic
nodules with a connective tissue capsule
around them.
6. Lymph node structure:
a. Surrounded by a connective
tissue capsule - trabeculae that
extend radially into the node
b. A subcapsular sinus separates the
cortical stroma from the connective
tissue capsule.
c. The dense cortical stroma
consists of numerous lymphatic
nodules.
d. A less dense medulla consisting
of lymphocytes arranged in
strands called medullary cords.
* Lymph sinuses in medulla
* Cords and sinuses extend
toward a central hilus that is
essentially a large trabecula
connected to the connective
tissue capsule.
** Arteries enter and veins and lymph
vessels exit through the hilus
** Blood vessels branch into the
cortical regions from arteries in the
hilus - these give rise to "bulbs" of
capillaries within the germinal centers
of lymph nodules
** Lymph sinuses in the medulla empty
into lymph vessels that exit via the
hilus.
7. Between the cortex and medulla is the
paracortical region or thymus dependent
zone of the node that contains densely
packed cells that are mainly T-lymphocytes.
a. This region lacks lymphocytes in
animals that have had the thymus
removed at birth.
8. Cells outside the paracortical region are
mostly B-lymphocytes.
Normal lymph node
http://www.auburn.edu/academic/classes/zy/hist0509/index_histology.html
http://www.siumed.edu/~dking2/crr/CR034b.htm
http://www.path.sunysb.edu/hemepath/tutorial/normal_node/nl_node_image.htm
C. Tonsils - 3 types that are defined by
their structure and their location in
mouth and pharynx.
1. Palatine tonsils
a. On left and right in rear area of
oral cavity.
b. Dense lymphoid tissue that forms
a band of lymphatic nodules that lie
just below stratified squamous
epithelium.
c. Overlying epithelium forms
invaginations called crypts that
penetrate into the band of nodules.
http://commons.wikimedia.org/wiki/File:Throat_with_Tonsils_0011J.jpeg
1. Palatine tonsils
d. These crypts act as collecting
places for cellular debris and bacteria
as well as a place where live
lymphocytes and macrophages can
wander about.
e. The band of lymph nodules is
separated from underlying tissues by
a partial capsule of dense connective
tissue.
http://www.entusa.com/oral_pictures_htm/acute_tonsillitis_2.htm
Portion of a palatine tonsil
http://www.udel.edu/Biology/Wags/histopage/colorpage/cly/cly.htm
2. Pharyngeal tonsils (Adenoids)
a. Lie beneath a typical ciliated pseudostratified
columnar respiratory epithelium in rear roof of
pharynx.
b. Diffuse lymphoid tissue containing nodules,
but no crypts.
c. A thin capsule of dense connective tissue
underlies the lymphoid tissue.
http://hcd2.bupa.co.uk/images/factsheets/Tons_aden_uvul_427x240.jpg
http://www.udel.edu/Biology/Wags/histopage/colorpage/cly/cly.htm
3. Lingual tonsils
a. Situated at base of tongue.
b. Each lingual tonsil consists of numerous. lymphoid nodules surrounding a single
crypt
non-keratinzed
c. The crypt is lined by a stratified squamous epithelium.
http://www.georgetown.edu/dml/educ/micro/lymph/9.htm
D. Thymus
1. Location - situated over the heart where
great vessels connect.
2. Important during early life when the cellular
mediated component of the immune system
develops. Undergoes atrophy in later life, at
which time it loses its functional significance.
3. The thymus can be considered a
proliferation and maturation center for Tlymphocytes.
4. The thymus consists of multiple lobes each
containing a cortical and medullary region.
5. A connective tissue capsule surrounds the
thymus.
http://www-micro.msb.le.ac.uk/MBChB/2b.html
7. Thymus - general structure
thymic lobule
The cortical and medullary
zones of lobules are
continuous.
8. Cell types found in the active thymus are:
a. T-lymphoblasts - stem cells for additional tlymphocytes - mitotically dividing.
b. T-lymphocytes
c. Reticular cells
d. Macrophages
e. Plasma cells
f. Mast cells
g. Unidentified mesenchymal cells
http://www.lab.anhb.uwa.edu.au/mb140/CorePages/Lymphoid1/Lymph1.htm
9. Cortical layer of thymus
a. Site of T-lymphocyte production - divisions of tlymphoblast cells.
b. Thus, there is considerable mitotic activity of tlymphoblasts
c. Reticular cells are less numerous in this area and
have thin and long processes that envelope groups
of developing thymocytes.
Reticular cells isolate groups of dividing and maturing
young animals.
t-lymphocytes in
10. Medullary zone
a. Contains many reticular cells and fewer Tlymphoblasts and lymphocytes than the cortex.
b. Also contains specialized structures known as
Hassall's corpuscles - function not certain*
Consist of a central, eosinophilic, hyaline core
surrounded by concentric layers of reticular cells
Potent source of cytokine -thymic stromal
lymphopoietin (TSLP) that directs maturation of
dendritic cells.
http://med-ed.med.virginia.edu/med-ed/
histology/imagedisplay.cfm?file=Cell0376
http://www.lab.anhb.uwa.edu.au/mb140/CorePages/Lymphoid1/Lymph1.htm
11. Blood supply
a. Branches from the internal thoracic and inferior thyroid arteries penetrate the capsule
surrounding the thymus
b. Extend into thymus along interlobular septa.
c. Capillaries branch into the cortico-medullary junction area and extend into the cortex.
d. These eventually extend into the medulla where they drain into venules
e. Venules connect to veins that exit thymus along connective tissue septa.
f. There are no afferent lymphatic vessels connecting to the thymus. So it does not act as
filter for lymphatic fluids.
g. Only a few efferent lymphatic vessels are present, and these are associated with the
blood vessels.
Precursor t-lymphocyte stem cells migrate from bone marrow to thymus entering the
organ via blood vessels in medullary zone. These cells undergo mitosis and maturation
in cortical zone and then leave thymus through blood vessels of medullary zone to go
about their various activities.
12. Blood-thymus barrier - only present in the cortex, acts to prevent most blood born foreign
antigens from reaching developing thymocytes. - presumed important in allowing Tlymphocytes to develop properly.
This barrier consists of :
a. Non-fenestrated, continuous endothelium of blood capillaries
b. Desmosome connections forming tight junctions between adjacent endothelial cells of
capillaries, as well as similar connections between surrounding reticular cells
c. Pericytes and reticular cells that form a sleeve around the capillaries in addition to
surrounding connective tissue.
d. Thick basal lamina from reticular cells that surround capillaries
e. Macrophages that are present in the surrounding connective tissue.
In the medulla, the sheath cells of the blood-thymus barrier are lost and vessels become
permeable - cells can move in and out.
E. Spleen
1. General characteristics
a.
Largest piece of lymphatic
tissue in body.
b. Can be said to act as filter of blood both in an
immunologic sense and also in the sense of
removing worn out erythrocytes from circulation.
http://www-micro.msb.le.ac.uk/MBChB/2b.html
2. Functions of the spleen
a. Production of blood cells during embryogenesis
* In embryo, erythrocytes, neutrophils, basophils, and eosinophils are produced in
spleen. This stops about the time of birth.
b. Destruction of erythrocytes
* Worn out erythrocytes are phagocytosed and digested by
macrophages in the spleen.
* Hemoglobin is broken down into bilirubin (open chain of four pyrroles
rather than ring of 4 pyrroles as in heme group) and ferritin.
Bilirubin
c. Recycling of ferritin from worn out erythrocytes for synthesis of hemoglobin
* Bilirubin is returned to the blood and carried to the liver where it is excreted and
passed out of body as part of the bile.
2. Functions of the spleen
d. Immune response
* Site of activation of both T- and B-lymphocytes
* These cell types interact with dendritic cells (form from monocytes) that act as antigen
presenting cells.
e. Storage of erythrocytes that can be released into circulatory system when needed.
3. Structure of spleen
a. Surrounded by a dense connective
tissue capsule that extends processes
(trabeculae) into lymphatic tissue of this
organ.
* Connective tissue contains nerves,
blood vessels,lymph vessels, and
smooth muscle.
* A hilum (hilus) of connective tissue is
present medially.
* Blood vessels and nerves run through
the hilus and enter the spleenic pulp via
the trabeculae. There are no lymph
vessels in the pulp.
* Pulp is divided into lymphatic nodules of
white pulp, surrounded by a spongy
lymphatic tissue called red pulp.
* Color designations have to do with
appearance in freshly cut open organ.
http://www.lab.anhb.uwa.edu.au/mb140/
b. Red pulp
* Forms spongy reticular tissue
that is composed of cords of
cellular (connective) tissue
that surround blood sinusoids
(cavities).
http://www.vh.org/Providers/Textbooks/MicroscopicAnatomy/Section09/Plate09172.html
http://medocs.ucdavis.edu/CHA/402/studyset/lab9/list.htm
http://www.vh.org/Providers/Textbooks/MicroscopicAnatomy/Section09/Plate09175.html
* Blood sinusoids are present - sites of
cellular exchange between spleen and
circulatory system. Cells can enter or
leave spleen through large spaces
between endothelial cells lining
sinusoids.
* Cell types present - macrophages,
monocytes, lymphocytes, plasma cells,
and various other blood cells (i.e.
granulocytes and erythrocytes).
* Supported by a network of reticular
cells and their associated fibers.
* The “strands” of reticular
connective tissue between blood
sinuses in red pulp are called the
cords of Bilroth. The reticular C.T.
supports the cells associated with
it.
http://www.vh.org/Providers/Textbooks/MicroscopicAnatomy/
Section09/Plate09175.html
Theodore Billroth, Austrian
surgeon (1829 - 1894) - father
of abdominal surgery.
http://medocs.ucdavis.edu/CHA/402/studyset/lab9/list.htm
http://www.lab.anhb.uwa.edu.au/mb140/
c. White pulp
*Concentrations of lymphatic
tissue within the red pulp that
surround portions of central
arteries and form lymphatic
nodules.
*Nodules consist of reticular mesh
with spaces in mesh being filled
with lymphocytes and some
macrophages. “Central” artery is
identifying characteristic.
* Both B- and T-lymphocytes in white
pulp. T-lymphocytes in sheath
surrounding central artery (periarterial
lymphatic sheath - PALS), Blymphocytes in white pulp
surrounding sheath (i.e. peripheral
white pulp - PWP) and in the germinal
center of the nodule.
* Other cell types present - monocytes,
plasma cells.
http://www.lab.anhb.uwa.edu.au/mb140/
http://www.vh.org/Providers/Textbooks/MicroscopicAnatomy/Section09/Plate09172.html
*Marginal zone surrounds white
pulp nodules - contains few
lymphocytes, but many actively
phagocytic cells with branching
processes (dendritic cells antigen presenting cells).
*Marginal zone acts as a filter to
pull foreign antigens out of blood
so that lymphocytes can react to
them and be induced to
participate in an immune
response.
http://www.upei.ca/~morph/webct/Modules/Lymphoid/spleen.html
The End