Download 3-4 (Bebok)

H & E: 3:00 - 4:00
Scribe: Caitlin Cox
Tuesday, October 20, 2009
Proof: Marjorie O’Neil
Dr. Bebok
Immune System #2
Page 1 of 5
APCs – antigen presenting cells; CT – connective tissue; Ag – antigen; HEV – high endothelial venules;
RBCs – red blood cells; PALS – periarterial lymphatic sheath/system
I.
II.
III.
IV.
V.
VI.
VII.
Immune System #2 [S1]:
a. Skipped.
Role of the primary lymphoid organs [S2]:
a. This is the most important sentence to remember about the previous lecture: primary lymphoid organs provide
sites for lymphocyte maturation where they become antigenically committed in the absence of the antigens.
Mature B and T cells [S3]:
a. Mature B and T cells will carry surface receptors depending on what type of cell they are.
b. They are antigenically committed.
c. They are small lymphocytes that you cannot distinguish by simple staining.
d. They are carried by blood or lymph to the secondary lymphoid organs.
Secondary Lymphoid Organs [S4]:
a. The secondary lymphoid organs are scattered throughout the body, which is why they can provide systemic
protection against infectious agents and foreign substances.
b. Lymph nodes are scattered throughout the body. They are present:
i. in different regions of the subcutaneous area.
ii. close to the hilum of organs, like the lungs.
iii. along the sides of the trachea and esophagus.
iv. in the axillary, inguinal, and retroperitoneal regions.
v. on the sides of the aorta and inferior vena cava.
vi. They are usually close to the blood vessels because the arteries, veins, and lymphoid vessels run together.
vii. The main function of the lymph nodes is to filter the lymph.
viii. Lymph vessels start blind in the tissue spaces. Lymph nodes are in the way of the lymphoid vessels and
so the lymph is filtered through these lymph nodes.
c. The spleen is located on the left side under the diaphragm. Its main function is to filter the blood.
d. The third secondary lymphoid tissue is the lymphoid follicles and larger conglomerates of lymphoid follicles that
are associated with specific organ systems. These are the Mucosal Associated Lymphoid Tissue (MALT) and
the GI tract Associated Lymphoid Tissue (GALT). These are the parts of the secondary lymphoid system that
provide the first defense against external antigens that reach our system either through alimentary Ags or
through the air if they are present in the respiratory system.
Organization of secondary lymphoid tissues [S5]:
a. The secondary lymphoid organs have special organization.
b. If it is just a diffuse collection of lymphocytes, macrophages, and other accessory cells in different organs and
the lamina propria, then you usually will see dark, small lymphocytes in a small concentrated area.
c. Lymphoid follicles are aggregates of lymphoid cells which contain both B and T cells and APCs. It has all the
cells of the immune system. Lymphoid follicles are surrounded by lymphoid capillaries because lymphoid
capillaries are the first system that the lymph flows through.
d. Lymph nodes are more highly organized secondary lymphoid organs. They have a stroma, which is composed
of reticular cells. In the openings and…. (inaudible word at min 5:21) ….will lie the lymphocytes, macrophages,
and APCs.
e. The spleen has a capsule. It is a separate organ; it is not in close association with other organ systems.
Lymphatic system [S6]:
a. The lymphatic system starts blindly in the tissue spaces.
b. From the tissue space, the lymphatic capillaries collect Ags that come through the alimentary tract or the skin to
reach our system.
c. The lymphoid capillaries will carry the Ag to the lymphoid follicles or to the lymph nodes, which have hundreds
of lymphoid follicles covered by a CT capsule.
Lymph Nodes [S7]:
a. This is a cartoon of a cross-section of the lymph node.
b. Lymph nodes have a CT capsule. The CT capsule will send its trabeculae deep into the lymph node. The
trabeculae are connected to the reticular cells, which compose the stroma of the lymph node.
c. What is important is that the convex part of the lymph node is where the afferent lymphatic vessels (which carry
lymphocytes and Ags) will reach the lymph node by piercing the capsule and opening into the marginal sinuses.
d. The marginal sinuses are where the Ags and the lymphoid cells will reach the lymph node. From there, the cells
and the Ags will move down from the trabecular sinuses because the CT of the trabeculae moves down and the
sinuses follow.
H & E: 3:00 - 4:00
Scribe: Caitlin Cox
Tuesday, October 20, 2009
Proof: Marjorie O’Neil
Dr. Bebok
Immune System #2
Page 2 of 5
e. From the sinuses, the cells can migrate out into the lymph node where we will distinguish between B cell zones
and T cell zones. The end of the lymph node where the efferent lymphatic vessel leaves the lymph node is
called the hilum.
f. Very important to understand that in the immune system in real life, the cells in lymph nodes are constantly
moving and bumping into each other. This is how the T cells meet with the APCs so they can recognize the Ag
presented specifically for that particular T cell. This is how the B cells meet the Ag that is carried in the lymph.
This is how the memory cells can go from one part of the body to another. If the Ag meets that particular
memory cell in a different region, it can recognize it. These cells (lymphocytes, APCs, macrophages) are
constantly moving between the different lymphoid organs of the system.
VIII. Lymph node [S8]:
a. This is a low magnification cross-section of the lymph node.
b. Underneath the capsule, you see the more open area, this is the marginal sinus. It reaches down following a
trabecula of CT. She pointed out the trabecular and medullary sinuses.
c. The darker areas are the medullary trabeculae of the lymph node.
d. Right under the marginal sinus or “subcapsular sinus,” the area with the conglomeration of dark, small
lymphocytes with the light center is the B cell zone of the lymph node. This area represents the secondary
lymphoid follicle.
e. Each lymph node contains hundreds of lymphoid follicles. A lymphoid follicle is the B cell area of the lymph
node. If the center of the lymphoid follicle is lighter, then the cells are proliferating and the lymphoid follicle is
active. The center that is lighter is called the germinal center.
f. This picture shows the different areas of the lymph node. There is no real border between the B and T cell
zones. There are lots of APCs in between them that can move and find the antigen they are specific for.
IX. Secondary Lymphoid Follicle [S9]:
a. This is a higher magnification of the secondary lymphoid follicle. Remember that a lymphoid follicle is part of a
lymph node, and there are many of them in one lymph node.
b. The germinal center is where the cells are proliferating. Once the B cells are activated, they start to divide and
grow larger. The nucleus also grows larger because the chromatin is more diffuse. This is why the germinal
center area is lighter in color—because the cells are larger and the nuclei are larger and lighter.
c. Germinal center formation occurs when the cell that was specific for a certain Ag met that certain Ag and started
to proliferate. Each center is responsible for the development of one specific B cell that will later develop into
the plasma cell that will secrete antibodies. It is believed that in each center, only one Ag specific B cell will
proliferate, so each germinal center is responsible for the development of one specific antibody.
d. This darker area is the mantle zone. These are small lymphocytes that have not met their specific Ag yet. If this
particular lymphocyte meets the Ag, it will start to form a germinal center around it.
X. HEV [S10]:
a. Around the follicles is the T cell zone. In the T cell zone of any secondary lymphoid organs, we see this very
interesting structure called high endothelial veins (HEV).
b. Lymph nodes are vascularized. Although the lymph nodes are responsible for filtering the lymph, the cells are
able to move between the lymphoid vessels and the blood vessels in the lymph nodes. These HEV are the sites
of the movement of cells between the lymphoid system and the blood stream.
c. The cells can move both directions: they can come out of blood into the lymph node, meet the Ag, and get
activated or cells from the lymph node can get into the blood stream and the blood can carry those cells that
have been activated into the tissue spaces where the cells get filtered out and start to proliferate there to provide
the systemic response.
d. HEVs are the sites where the lymphoid system and the circulatory system meet in the lymph nodes. They are
more numerous around the follicles in the T cell areas of the lymph nodes.
e. They are endothelial cells that carry endothelial cell markers, but they don’t look like endothelial cells because
they are taller. Endothelial cells of capillaries would be flat, and you would not see the cell so well. The
difference here is that they are higher, they look like cuboidal cells, but they are blood vessels, they are venules.
XI. Reticular cells and macrophages [S11]:
a. This is one of the sinuses (marginal, subcapsular or trabecular). What is important is that the sinuses are
spanned by reticular fibers. Reticular fibers are produced by reticulocytes, and these fibers span through the
wall or the capsule of the lymph node.
b. The inner area is where there are more lymphocytes, and the fibers form a network in which the cells lie.
c. In the sinuses, you see a bunch of macrophages and debris. You cannot distinguish between macrophages
and APCs in this slide because you can only tell the difference when the cells are stained for MHC II, which only
presents on the surface of the APCs. If this phagocyte is MHC II+ which binds to CD4, then these are APCs.
They can migrate into the stroma of the lymph node, stay there, and present the Ag. If they are just
H & E: 3:00 - 4:00
Scribe: Caitlin Cox
Tuesday, October 20, 2009
Proof: Marjorie O’Neil
Dr. Bebok
Immune System #2
Page 3 of 5
macrophages that function solely to chew up the Ag, then they just move around with the lymph to other tissues
and phagocytose and destroy Ags.
d. Silver staining of the tissue shows the reticular fibers, which stain black.
XII. Lymph Nodes (B cell activation) [S12]:
a. Lymph nodes filter the lymph. The Ag enters the lymph node through the afferent lymphatic vessels. Then it
reaches down into the T and B cell zone where the Ag meets the cells, and it either meets the right cell or not. If
they do meet, that particular cell starts to proliferate.
i. If it is a B cell, it will develop into a plasma cell. The plasma cells will move down into the trabeculae in the
medullary region of the lymph node. Here (pointing at diagram) you see the B and T cell zone, this is the
cortex. There you see the trabeculae and lots of sinuses; this area is the medullary region of the lymph
node. The plasma cell will secrete the antibodies into the sinuses in the medulla.
b. The B and T cells are able to leave the lymph node through the efferent lymphatic vessel.
c. Remember that the blood stream and the lymphatic circulation are connected in the lymph node in the T cell
area at the specialized structure called the HEV. Through the wall of the HEV, the T and B cells and
macrophages can migrate in and out, and that is how the connection between the blood stream and lymphatic
vessel happens.
XIII. Spleen [S13]:
a. The spleen is a secondary lymphoid organ that filters blood. The spleen is located on the left side underneath
the diaphragm.
XIV.
Spleen [S14]:
a. It looks like a large bean-shaped organ that has a hilum. This is where the splenic artery reaches the spleen
and where the splenic vein leaves the spleen. The spleen is covered by CT capsule. The Ags will reach the
spleen through the lymphatic artery and the splenic artery.
XV. Spleen #2 [S15]:
a. This is a cartoon of a cross-section of the spleen. It is covered by a CT capsule that sends these trabeculae
(pointing at the diagram) down deep into the organ. After it reaches the hilum of the spleen, the artery divides
into smaller branches. The spleen arteries will run in the center of the lymphatic tissue.
b. The area that surrounds the splenic arteries is the T cell zone (meaning that it contains mostly T cells); this area
is also called the periarterial lymphatic system or sheath (PALS).
c. Outside of the T cell zone we will find B cell zones or lymphatic follicles, depending on whether it is active or
inactive. It is a conglomerate of B cells, and if one of them gets activated, it starts to proliferate and form the
germinal center. If they are not activated, it is just small dark lymphocytes; it is darker than the surrounding
area.
d. Outside of the B cell zones, we see the marginal zone where there are lots of sinusoids. Sinusoids are where
the cells are moving in and out in between the vessels.
e. The white pulp of the spleen is the lymphatic system of the spleen. The white pulp (which can be divided into
the T cell zone (PALS), lymphatic follicles, and marginal zone) is located right around the arteries that divide in
the spleen.
f. Outside of the white pulp is the red pulp, which is responsible for the destruction of old RBCs. The red pulp has
trabeculae full of macrophages that phagocytose the filtered out RBCs. The macrophages contain a lot of iron
pigment because of the destruction of the RBCs. They will either store the iron or release it to bind to transferrin
to be delivered throughout the entire system.
g. The two functions of the spleen are to act as a secondary lymphoid organ and to filter Ags from the blood.
XVI.
Spleen structure [S16]:
a. This just shows you again that the lymphatic part (the white pulp) of the spleen surrounds the artery. The
central artery is what runs in the center of this white pulp (or lymphatic tissue) of the spleen. If you see a tissue
section with lymphoid tissue and there is an arteriole cross-section in the middle, you know it is the spleen. You
will not see a cross-section of an arteriole in the lymph nodes. This is a good tool to identify the spleen when it
is a high magnification section and you cannot see the red pulp or capsule.
b. After piercing through the PALS, the arteries will reach out into the red pulp to form sinusoids, which is where
the RBCs will be filtered out. The RBCs from the lumen will be filtered out into the trabeculae where there will
be macrophages to phagocytose and destroy them.
XVII. Histology of spleen #3 [S17]:
a. This is characteristic histology of the spleen. This is the central artery. Around it is the PALS. There is a
lymphoid follicle (B cell zone) with a small germinal center. The larger openings are the sinusoids of the red
pulp.
XVIII. Histology of spleen #2 [S18]:
a. This is better in order to distinguish between the lymphatic system organs because here you see the central
artery cut almost longitudinally. It reaches to the periphery; this is the lymphoid system that surrounds it.
H & E: 3:00 - 4:00
Scribe: Caitlin Cox
Tuesday, October 20, 2009
Proof: Marjorie O’Neil
Dr. Bebok
Immune System #2
Page 4 of 5
b. Out here, you see the marginal zone, a sinusoid, and red pulp.
c. The names white and red came from the color of the cut surface of the spleen when removed from the cadaver.
However, when sectioned and stained with H&E, the white pulp becomes redder while the red pulp gets bluish.
Don’t get confused.
XIX.
Structure of the red pulp [S19]:
a. Here I show you only the red pulp. The red pulp, see the red dark area (this is a PAS stain), it shows the pulp
cord. The openings are the sinusoids. Macrophages are always moving, so they are in the lumen and can
move into the pulp cords and rest for a while and digest the RBCs. They can stay there for a while and store the
iron, but that is what they look like with the pulp cords and the sinusoids in the lumen.
XX. EM structure of the splenic sinuses [S20]:
a. This EM shows you how the wall of the sinusoids is organized. Fusiform cells form the lumen of the sinusoid.
She pointed out the lumen and the pulp cords. The way they are organized is that the wall looks like a barrel
because the cells are elongated. In between the cells, the RBCs and macrophages can migrate out. This is
how they migrate in between the lumen and the pulp cords.
XXI.
Functions of the red pulp [S21]:
a. Here we see RBCs in the cytoplasm of the macrophages. They have phagocytosed the RBCs and will digest
them.
b. The RBCs that are filtered out are recognized based on their cell-surface protein. Many of the cell-surface
proteins are glycoproteins and the glycan moiety of these proteins is changing. One small galactose being
exposed is the recognition for these cells that they are too old. Then they are filtered out in the spleen and
destroyed by the macrophages.
XXII. Blood Flow Through The Spleen [S22]:
a. This is just a sequence of slides to help you understand how the blood flows through the spleen.
XXIII. Black and White Diagram [S23-73]:
a. Blood comes in through the splenic artery, goes into the central artery, reaches through the lymphatic tissue,
and goes out through the red pulp.
b. It is still not completely sure if some parts of the blood vessels just open into the pulp cords (Open Circulation).
c. Or if they are just connected to the venous sinuses, which collect together and connect to the splenic vein
(Closed Circulation). Closed circulation says that they are directly connected together without leaking out into
the tissue spaces.
d. Some of the Ags can be filtered out through the marginal sinuses and get into the lymphatic tissues. That is
how the Ag filters out into the lymphatic zone—through the marginal sinuses. These are arteries and arterioles;
the wall is too thick for the Ags and the cells to be filtered out. So it is believed that once they reach out here
into the marginal sinus that is the sign for the lymphatic cells to migrate out into the PALS and meet the
lymphoid cells, and the immunoglobulins produced by the plasma cells in this area can be delivered into the
bloodstream. This is how the Ags come back from the red pulp.
e. We can see the iron comes back into the blood stream and is being delivered. The role of the marginal sinus is
where the cells and Ags can be filtered out into the lymphatic area.
f. It does not show that the T and B cells are actually in close connection with each other; they are not separated
by lines or any kind of margins from each other.
XXIV. MALT—Tonsils [S74]:
a. The organ system associated with the MALT is the tonsils. These are the lymphoid organs that meet the Ags
that reach us from the outside. The tonsils surround the openings of the GI and respiratory tracts. There are
different types of tonsils based on their location. The three types of tonsils are the: palatine, lingual, and
pharyngeal tonsils.
b. These are just collections of lymphoid follicles. The difference between tonsils and lymph nodes are that lymph
nodes have a specific structure with a capsule and there are afferent lymphatic vessels reaching the lymph node
and efferents leaving it. The tonsils do not have the afferent lymphatic vessels and capsule because the Ag
reaches them directly from the outside. So they do not have to have the lymphatic system to deliver the Ags to
them.
c. Instead of having lymphatic vessels coming to them, they have crypts, or mucosal folds, to which the Ag is being
delivered. The Ag migrates into the tissue through the cells which actually reach out and catch the Ag in the
crypt. Close to the tonsil so the cells meet the Ag and the cells start being activated. Tonsils do not require the
blood stream or the lymphatic circulation to deliver the Ag to them.
XXV. Tonsils [S75]:
a. The lingual tonsils are located in the dorsal part of the tongue (represented by the purple area in the diagram).
b. You can see the crypts that reach down into the tonsil.
c. The blue flower looking structure represents the lymphoid follicles, each of the B cell zones. The light blue
around them is the T cells.
H & E: 3:00 - 4:00
Scribe: Caitlin Cox
Tuesday, October 20, 2009
Proof: Marjorie O’Neil
Dr. Bebok
Immune System #2
Page 5 of 5
d. There are many lymphoid follicles in the tonsils just like in the lymph node.
e. The pharyngeal tonsil is located in the back of the nasal cavity.
f. How can you recognize the different types of tonsils? Depending on where they are located, the surface
epithelium represents that area of the GI tract or respiratory tract. The tonsil that is in the tongue will be covered
with oral epithelium, which is stratified squamous nonkeratinized epithelium.
XXVI. Palatine Tonsils [S76]:
a. The palatine tonsil with have more of a lymph node structure because it has CT tissue surrounding it on the
inside not the outside surface. The palatine tonsil is also covered by oral epithelium, but the difference between
the lingual and the palatine is the thick CT at the bottom of the lymphoid follicles of the palatine tonsil.
XXVII. Palatine tonsil histology [S77]:
a. This is a higher magnification. In the palatine tonsils, right underneath the CT, you may see glands that secrete
saliva.
XXVIII. [S78-80]:
a. She basically skipped these; she repeated a few things she had already said, so I did not transcribe them again.
XXIX. Pharyngeal Tonsil – Adenoid [S81-82]:
a. The only difference of the pharyngeal tonsil is that it will be covered with respiratory epithelium (pseudostratified
ciliated columnar epithelium).
b. The cilia are partially or totally destroyed in these histological slides, but you can see the pseudostratified
columnar cells. We see the lymphoid tissue under the epithelium and the lymphoid cells infiltrating the
epithelium also.
XXX. Summary [S83]:
a. The main function of the tonsils is to provide the first defense against airborne and ingested Ags. They can be
recognized based on encapsulation and presence of the surface epithelium depending on where they are.
XXXI. Clinical Correlations [S84]:
a. They often inflame and have to be removed.
XXXII. [S85-88]:
a. This is just repetition of the same things because these are all part of the secondary lymphoid system. This is
the lymphoid tissues that are associated with the GI tract. I will not talk about this in detail because we don’t
have time but you will have a couple of slides to look at (aka: she wants us to read these slides on our own).
XXXIII. Functions of the secondary lymphoid tissues [S89]:
a. Just like she emphasized the function of the primary lymphoid organs at the beginning of lecture, she
emphasized this sentence: they capture antigens and provide sites where the lymphocytes undergo clonal
proliferation and differentiation into effector cells in the presence of the antigen. This is the main difference
between primary and secondary.
XXXIV. Summary [S90]:
a. The last slide is what everyone has to know for the exam.
[end 47:12 min]