Term
Distinguish between primary and secondary lymphoid organs, providing the primary examples of each.
Which organ is a mix of the two and why? |
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Definition
PRIMARY (antigen-free zones where immune cells are produced)- Bone marrow and Thymus
SECONDARY (where reaction takes place)- Lymph nodes, spleen, tonsils, mucosal-associated lymphoid tissue (MALT), digestive/respiratory tracts.
2) Gut Associated Lymphoid Tissue (GALT) possesses elements of both in that it involves negative T-cell selection (primary), but is not sealed off completely from antigens (secondary). |
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Term
| True or False: B-cell mediated phagocytosis is a form of cell-mediated immunity |
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Definition
True!
Even though B-cells produce Ab, which are part of the humoral, adaptive immune response, they are also involved in cell-mediated immunity. |
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Term
| What are the 4 major functions served by lymphoid organs? |
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Definition
Integers Cant Contain Decimals (ICCD)
1) Isolated environment for maturation
2) Concentrate lymphocytes in organs thats drain other organs experiencing antigenic insults (i.e. lymph nodes)
3) Control immune cell interactions
4) Distribution of antibodies and immune active cytokines |
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Term
| What is the most abundant cell type in normal bone marrow after RBCs and granulocytic precursors? |
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Definition
Every 1 of 2000 bone marrow cells is a stem cell
Lymphocytes 5-15%
Plasma 1%
Monocytes 4%
Megakaryocytes 4% |
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Term
| How and where are self-reactive B-cells eliminated? |
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Definition
By the time of birth, self-reactive B-cells have undergone negative selection and apoptosis in the bone marrow.
IL-7 released by stromal cells of the bone marrow regulate B-cell maturation and gene rearrangement.
Remember, most marrow is replaced by fat in mid childhood. |
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Term
| Explain how immature T-lymphocytes of the bone marrow become mature, differentiated T-cells in the Thymus. |
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Definition
1) Immature T lymphocytes (parenchymal cells called thymocytes) arrive at the subcapsular cortex (these cells double negative for CD4 and CD8)
2) Thymocytes migrate to to deep cortex, becoming double positive for CD4 and CD8. There are low levels of TCR-ab here.
3) Immunocompetent, double positive cells mature and differentiate Th (CD4- recognize foreign) and Tc (CD8- recognize self) populations before arriving in the medulla. In the medulla, there are high levels of TCR-ab
** At the same time, these T-cells are rearranging genes to produce TCRs** |
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Term
| Describe the 3 types of epithelial reticular cells that make up the Stroma of the thymic cortex. |
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Definition
Cytoplasmic extensions of these cells create antigen barrier, since there is no ECM
1) Possess tight junctions to seal the cortex from the capsule, the trabeculae and from the penetrating blood vessels
2) Link together by desmosomes to subdivide the thymic cortex into small lymphocyte-filled compartments. Present MHC 1 self antigen (self antigen).
3) Found at cortico-medulary junction (linked together by tight junctions). Present MCH 2 self antigen (foreign) |
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Term
| What do thymulin, thymopoietin, a1-thymosin, b4-thymosin-b and IL-7 have in common? |
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Definition
| These are thymic hormones secreted by stromal cells of the thymic cortex that act as local factors for T cell maturation. |
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Term
| Explain both how and where both positive and negative selection occur in thymic T-cell maturation. |
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Definition
This is Central Tolerance
Cells that recognize MHC I (self) by CD-8 and MHC II (foreign) by CD-4, and that do not recognize self epitopes survive and exit the thymus (98% are phagocytosed)
1) Negative selection occurs in the inner cortex and the medulla in order to eliminate T lymphocytes whose TCRs recognize self-proteins (epitopes).
2) Positive selection occurs in the outer half of the cortex and requires that T cell CD4 or CD8 molecules recognize MHC II or MHC I molecules, respectively (produces by type II and type III epithelial reticular cells. |
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Term
| What does it mean that T cells which exit the thymic cortex are "mature" but "immunologically naive"? |
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Definition
| They are differentiated, CD4 and CD8 presenting T-cells but they have not committed to any particular antigens, and will not do so until they travel to secondary organs and develop antigenic responsiveness. |
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Term
Describe the 3 types of epithelial reticular cells that support the thymic medulla.
Which type is useful in identifying thymic tissue? |
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Definition
IV) cortico-medullar junction
V) form cytoreticulum to support medulla
VI) coalesce into pale-staining Hassall's corpuscles (diagnostic features with unknown function) |
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Term
| What is significant about the Gut Associated Lymphoid Tissue (GALT)? |
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Definition
GALT is a lymphoid organ with properties of both
Primary (thymus-independent T cell development with positive and negative selection occurring in aggregated lymphoid nodules of the ileum called Peyer's patches)
and
Secondary (antigen exposure and activation) lymphoid organs. |
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Term
| What are the primary functions of lymph nodes? |
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Definition
1) Site for phagocytosis and antibody production against antigens filtering in the lymph.
2) Support induction, proliferation and differentiation of lymphocytes
3) Allow for recirculation of lymphocyte populations and their cytokine secretions throughout different lymphatic vessels. |
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Term
What is the basic histological structure of a lymph node?
What anatomical characteristic if unique to lymph nodes (i.e. not shared by other secondary lymphoid organs)? |
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Definition
1) Composed of
Cortex (B cells/primary follicles-
IgM +IgD+ small inactivated cells that represent a reserve population)
Cortex/Paracortex (CD4+ T helper cells and B cells at 4:1)
Paracortex (High endothelial venules for T and B lymphocyte diapedesis from blood to lymph node)
Medulla (Entering and exciting blood vessels, lymphatic sinuses and clusters of exiting lymphoid cells called "medullary cords")
2) Possess both afferent and efferent lymphatic vessels |
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Term
| Explain the important immunological process that occurs in the Cortex of a lymph node |
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Definition
1) Immature, IgM+IgD+ B-cells called "primary follicles" are activated by antigenic stimulation.
2) Pale, "germinal center" forms and secondary follicle develops, from which a clonal population of a selected B cell proliferates into plasma and memory cell populations. |
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Term
| Explain the important immunological process that occurs in between the cortex follicles and the paracortex of a lymph node. |
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Definition
CD4+ T helper cells and B cells exist in ratio of 4:1.
Dendritic cells present antigens to antigen-native T cells in order to initiate T cell immune response. |
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Term
| Explain the important immunological process that occurs in the paracortex of a lymph node. |
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Definition
Contains high endothelial venules that serve as site of diapedesis of T and B lymphocytes from blood into lymph nodes.
These lymphocytes are emptied via efferent lymphatic drainage of the medulla and return to the venous circulation at the heart, traveling through arteries and capillaries and exiting once more through the next high endothelial venule.
Since antigen-naive T cells have half life of 8 days, they travel in and out of numerous lymph nodes in their life time. |
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Term
| Explain the important immunological process that occurs in the Medulla of a lymph node. |
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Definition
This is the lymphocyte exit site.
Activated lymphocytes, plasma cells and macrophages are held in reticular fiber mesh.
Contains entering and exiting blood vessels, lymphatic sinuses and clusters of exiting lymphoid cells (Medullary Chords). |
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Term
| What are the primary immunological functions of the spleen? |
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Definition
Blood filtering and RBC turnover
1) Removes aged or injured RBCs
2) Site for activation of lymphocytes
3) In fetal development, functions as hematopoietic organ (can resume this function if necessary in adults). |
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Term
| What is the periarterial lymphatic sheath (PALS) and how does it relate to the rather unique blood supply of the Spleen? |
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Definition
The PALS is Layer of lymphocytes that coat small trabecular arteries of spleen that have lost their tunica adventitia (called "central artery").
Terminal arterial capillaries either
1) Dump into the tissue space of the splenic parenchyma
2) Flow directly into the splenic sinuses, from which pulp is drained into larger veins that merge to form exiting splenic vein
** There are no afferent or efferent lymph nodes in the spleen because everything is carried in blood! ** |
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Term
| What are the major distinguishing features of the "White Pulp" |
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Definition
White Pulp (so called for its contents of lymphocytes) is composed of lymphocytes (2/3 of PALS are CD4+ T helper cells, 1/3 is CD8+ Tc cells).
These cells are immunologically naive and will become activated within the spleen
Edges are a marginal zone enriched in plasma cells, T and B cells, macrophages and dendritic antigen presenter cells.
2) Red pulp is composed of splenic sinus and splenic cords of Bilroth (collagen III reticular network that is enveloped by stellate extensions of reticular cells, isolating the collagen from platelets and preventing clotting)
Macrophages are found in chords, because this is where aged RBCs are phagocytosed |
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Term
| How do macrophages recognize aged RBCs in splenic chords of Red Pulp? |
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Definition
1) Loss of spectrin decreases RBC flexibility and prevents them from exiting the Red Pulp into the blood.
2) Old RBCs lose terminal sialic acid on transmembrane glycophorin and display galactose.
Asialoglycoprotein receptors on macrophages recognize the galactose and phagocytose the RBC, leaving iron bound to transferrin, heme converted to billirubin and excreted by the liver in the bile, and globin chains which are reduced to AA |
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Term
| What is the primary function of Mucosal Associated Lymphoid Tissue (MALT) |
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Definition
Secondary lymphoid organ- lymphocytes that have been exposed to antigens in Peyer's patches and subsequently matures in lymph nodes migrate here to dispose of foreign antigens.
Anatomically- MALT is non-encapsulated, loosely organized lymphocytes underlying epithelia of GI, respiratory, reproductive and urinary tracts
Plasma cells of MALT produce IgA, a dimeric antibody secreted into the lumen of these organs as first line of defense. |
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Term
| True or False: Neutrophils and Eosinophils re-circulate after delivery to target tissues. |
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Definition
False!
Monocytes and Macrophages DO re-circulate
Neutrophils and Eosinophils DO NOT re-circulate |
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Term
| How can you tell between Hematopoetic Stem Cells populations and Myeloid progenitors? |
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Definition
HSCs are CD34-
Myeloid precursors are CD34+ |
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Term
| Early in fetal life, where do the majority of stem cell populations reside? |
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Definition
Liver and Spleen
By birth, it has switched to the bone marrow |
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Term
| What are the 2 primary HSC niches in bone marrow and where do you find mature cells? |
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Definition
Osteoblast and Vascular (location of cells determined by FGF-4 and O2 signaling)
Most mature cells are found around Vascular, sinusoidal space. |
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Term
| Which part of the bone marrow contains most proliferating hematopoietic cells? |
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Definition
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Term
| What is the role of GALT in so-called "Peripheral Tolerance"? |
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Definition
May be the source of differentiated T cells to be exposed to food antigens (tolerance prevents widespread food allergies).
Intestinal epithelial lymphocytes (IELs) of the GALT appear to have different surface molecules and antigen recognition than thymus-derived cells |
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Term
| Why is the "central artery" of the spleen sometimes pushed into an eccentric position during an infection? |
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Definition
| If T-cells in the PALS discover an invador, they cause a secondary germinal center of proliferating B lymphocytes to form, which may push the central artery into an eccentric position). |
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Term
What are the major distinguishing features of the "Red Pulp"
What occurs in the splenic chords vs. splenic sinuses? |
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Definition
Red Pulp is composed of Splenic Sinuses and Splenic Chords (open ended circulation dumps in here).
Splenic chords are composed of collage III that is covered in reticular cells to prevent platelet access and possible clotting. This is the site where RBC turnover takes place
Splenic sinuses control splenic cell access to the blood |
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Term
| Why might removing someone's spleen be of clinical concern? |
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Definition
| RBC turnover can take place in the Liver, but without a spleen, patient's are often more susceptible to certain blood-borne bacterial infections. |
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Term
| What are 2 major functions of Epithelial Reticular cells in the thymus? |
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Definition
Positive selection in the outer cortex involving MHC-II and MHC-I presentation.
Negative selection in the inner cortex involving self-antigen presentation. |
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Term
| What are "primary" and "Secondary" lymph nodules in the lymph node cortex? |
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Definition
1) Primary is resting, mature B cells
2) Secondary is germinal center where mature, naive B cells have encountered antigens and are becoming plasma cells |
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Term
| What occurs in the Paratrabecular sinuses of the lymph nodes? |
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Definition
| APC antigen presentation. Below these sinuses, T-helper cells contact and then communicate with B-cells. |
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Term
| What is the blood supply of a lymph nodes? How do cells gain access to the LN from the blood? |
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Definition
Enter and Exit at the hilus
Macrophages, lymphocytes (B and T) exit the blood and enter the LN at high endothelial venues, |
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Term
| How can splenomegaly arise? |
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Definition
1) Intrhepatic issues such as cirrosis can back up venous drainage of spleen
2) Infrahepatic issues such as a portal vein thrombosis can back up venous drainage of spleen.
3) Pancreatitis (lying on top of splenic vein) |
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Term
| Explain how the blood supply of the spleen relates to its immune function. |
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Definition
1) As trabecular arteries enter spleen, they lose adventitia and gain T cell sheath to become PALS.
If the PALS encounter antigens, they can hand them off to B cells, which can cause an eccentric central artery.
PALS is surrounded by a marginal zone containing macrophages (came from open circulation) and memory B cells
The PALS is the white pulp. The rest of it is red pulp (closed and open circulatory systems), which is a good RBC resevoir.
2) These PALS can either end here and get dumped out lose into the spleen (open circulation), or continue on to become capillaries and then veins (closed)
3) In the case of closed circulation, they become sinusoidal capillaries and then veins. |
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Term
| Explain the structure of the red pulp (open and closed circulation). |
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Definition
Splenic chords= coated in collagen 3 covered by reticular cell extensions (if the collagen sees platelets, there can be clots!. RBC turnover
Splenic sinuses- Elongated sinusoidal capillaries for returning RBC and WBC to circulation. |
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Term
| How do M cells function in the Peyer's patch of the GALT? |
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Definition
B cells get from GALT to MALT!
M cells give antigens to DCs, which present them to T-cells, which stimulate B-cells.
The mature B cells then have to get out of the spleen. They home back to the MALT (urinary, gut, respiratory, reproductive ect.) |
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