Introduction to the Immune System IV and V

Question 1

Outline the path of the lymph flow, including the 4 major lymph vessels and the regions they drain. Explain a major clinical implication of the asymmetric pattern of lymph drainage.

Answer 1

• blood in the capillaries is under pressure, and so some fluid and WBCs leak out into interstitial space
• lymphatic vessels are blind-ended vessels that have overlapping endothelial cells to form flap valves. fluid can leak into lymph vessels, but it can’t leak back out
• the right side of the head drains into the right jugular trunk. Lymph from the right upper extremity and right chest drains into the right lymphatic duct. this and the right jugular trunk drain into the venous system at the junction of the right subclavian and internal jugular veins
• the lower limbs, pelvis, and most of the abdomen drain into the thoracic duct. Lymph from the left side of the head drains into the left jugular trunk, then into the thoracic duct. The thoracic duct also receives the lymph from the rest of the abdomen, left chest, and left upper extremity before draining into the venous system at the junction of the left subclavian and internal jugular veins.

Question 2

Why are lymphatic vessels blind-ended?

Answer 2

so fluid can leak into lymph vessels, but it can’t leak back out

Question 3

What areas drain into the right jugular trunk

Answer 3

right side of head

Question 4

What areas drain into the right lymphatic duct?

Answer 4

Lymph from the right upper extremity and right chest drains into the right lymphatic duct

Question 5

The right jugular trunk and right lymphatic duct drain into what?

Answer 5

the venous system at the junction of the right subclavian and internal jugular veins

Question 6

The right side of the head drains into what?

Answer 6

right jugular trunk

Question 7

Lymph from the right upper extremity and right chest drains into what?

Answer 7

right lymphatic duct

Question 8

What areas drain into the thoracic duct?

Answer 8

the lower limbs, pelvis, and most of the abdomen drain into the thoracic duct

Question 9

Where does lymph from the left side of the head drain into?

Answer 9

Lymph from the left side of the head drains into the left jugular trunk, then into the thoracic duct

Question 10

What drainage goes into the thoracic duct (left)?

Answer 10

• lymph that drained from the left side of the head, into the jugular trunk, and then into the thoracic duct
• The thoracic duct also receives the lymph from the rest of the abdomen, left chest, and left upper extremity before draining into the venous system at the junction of the left subclavian and internal jugular veins.

Question 11

What does the thoracic duct drain into?

Answer 11

the venous system at the junction of the left subclavian and internal jugular veins

Question 12

What are the pathways that lymphocytes use to travel between blood and tissues? Compare to pathways used by other WBCs (re-circulation vs one way street)

Answer 12

Lymphocytes can recirculate between blood and the tissues

• they develop in the bone marrow and then enter the circulation
• they leave the circulation at post-capillary venules
• they enter lymphatic vessels, travel through lymph nodes, and return to the venous circulation
• other WBCs cannot enter lymph vessels, and die in the tissues once they leave circulation

Question 13

What is the difference between primary and secondary lymphoid organs?

Answer 13

Primary lymphoid organs

• sites of B and T cell production
• they produce naive B and T cells
• thymus and bone marrow

Secondary lymphoid tissues

• sites in which naive B and T cells recognize antigen and launch an immune response
• tissues include lymph nodes, white pulp of the spleen, mucosa-associated lymph tissues (MALT) of the respiratory, gastrointestinal and urogenital tracts

Question 14

Describe the histology of bone marrow. Relate structure to function.

Answer 14

• surrounded by compact bone
• inside is spongy bone, or trabecular bone
• many sinuses and capillaries
• blood cell formation occurs in the trabecular space, and the cells exit the bone marrow via the sinusoids

Question 15

Describe the histology of thymus. Relate structure to function.

Answer 15

• lobular organ separated by thin septa
• each septa has a cortex (darker) and medulla (lighter)
• the cortex contains most of the developing T cells, while more epithelial reticular cells are present in the medulla
• epithelial and endothelial cells have tight junctions, forming a blood-thymus barrier to protect developing T cells from being exposed to foreign antigen
• macrophages are present in the medulla to digest any T cells that recognize self

Question 16

Describe the structure and function of lymphoid follicles. Distinguish lymphoid follicles from thymic lobules, both structurally and functionally.

Answer 16

• lymphoid follicles are the structural unit of all secondary lymph tissue
• in the thymus, T cells are developing and maturing into naive T cells. In lymphoid follicles, B cells are undergoing affinity maturation to select the best receptor for the antigen. Lymphocytes encounter antigens here.
• in the thymus, the organ is constructed of lobules that are separated by connective tissue septa. Each lobule has a cortex and a medulla. In lymphoid follicles, a round patch is there with T cells around the outer edge and B cells lining the center (mantle and germinal center)
• lymphoid follicles are the site of affinity maturation of B cells
• lymphoid follicles are also the site of antibody class switching by B cells, depending on location. All B cells start with IgM:
• – mucosal –> IgA
• – systemic –> IgG
• – parasitic infection or allergy –> IgE
• lympoid follicles are the site of proliferation as well as apoptosis; the thymus is the site of development and apoptosis for T cells
• post-capillary venules in lymphoid follicles have a cuboidal epithelium that selectively promotes lymphocyte entry into lymphoid follicles; called High Endothelial Venules (HEV); post- capillary venules int he thymus are normal

Question 17

What is the site of affinity maturation of B cells?

Answer 17

• lymphoid follicles are the site of affinity maturation of B cells
• -> once a B cell encounters an antigen, it proliferates rapidly into many different cells with similar antigen binding regions. Due to the speed of the proliferation, mutations occur, and they are not exactly the same. Thus, not each B cell has the same affinity for the antigen. The one with the strongest affinity will be selected, and the rest of the cells deleted. The strongest one will proliferate into pre-plasma cells that will leave the germinal center and mature into plasma cells.
• -> due to the amount of cell growth, and necessary apoptosis, histologically mitotic figures, macrophages and centroblasts (rapidly dividing lymphocytes) can be observed

Question 18

Due to the rapid amount of B cell proliferation in lymphoid follicles, and the necessary apoptosis, what histological features can be observed?

Answer 18

Due to the amount of cell growth, and necessary apoptosis, histologically mitotic figures, macrophages and centroblasts (rapidly dividing lymphocytes) can be observed

Question 19

What is the structure of lymphoid follicles (B and T cell locations)?

Answer 19

In lymphoid follicles, a germinal center and mantle separate T and B cells. B cells are concentrated in the germinal centers and inner mantle. T cells predominate in the outer mantle of lymphoid follicles

Question 20

Lymphoid follicles are also the site of antibody class switching by B cells, depending on location. All B cells start with IgM. What antibody class do B cells switch to for the followig:

• mucosal
• systemic
• parasitic infection or allergy

Answer 20

• lymphoid follicles are also the site of antibody class switching by B cells, depending on location. All B cells start with IgM:
• – mucosal –> IgA
• – systemic –> IgG
• – parasitic infection or allergy –> IgE

Question 21

Describe the structure and function of lymph nodes. Explain the special anatomic features that reflect the function of lymph nodes as filters of lymph.

Answer 21

Lymph node structure:

• sit on the path of lymph vessels (to filter lymph)
• covered with a capsule; trabeculae of CT cut into the node; there are sinuses underneath the capsule that drain lymph; lymphoid follicles are located in the cortex (which contain mainly B lymphocytes in the germinal center and the mantle)
• each lymph node is divided into a cortex and medulla
• T cells are located int he medulla
• Cells are organized into ‘cords’, which are anastomosing (connecting) linear clusters of cells supported by a framework of reticular cells and their fibers (type III collagen secreted by mesenchymal reticular cells)
• lymph enters the node through afferent lymphatic vessels, trickle through sinuses, then drain through a single efferent vessel
• mesenchymal reticular cells line the sinuses, creating turbulence that allows the contents of lymph to maximize contact with cells int he node (this allows APCs to present their antigen and have the best chance of finding a T or B cell that has a specificity for it and generating an immune response if appropriate)

Question 22

Afferent vessels flow _____ lymph nodes. Efferent vessels flow ______ lymph nodes.

Answer 22

afferent: into
efferent: out of

Question 23

What are possible causes of lymphadenopathy?

Answer 23

• swelling of the lymph nodes
• can occur due to infection elsewhere in the body (engaged in immune response)
• infected with pathogen
• colonized by cancer
• lymphocytes become neoplastic

Question 24

Describe the structure and function of the spleen. Explain the special anatomic features that reflect the function of the spleen as filter of blood.

Answer 24

• supported by thick CT capsule and struts of CT (trabeculae) that jut into the organ
• white pulp has functions in immune responses to blood borne pathogens (secondary lymph tissue); as blood spills out of arterioles into the spleen parenchymaa, macrohpages situated at the edge of red and white pulp ingest particulates and enter the white pulp to present antigen
• blood enters the spleen through the splenic artery, which branches into trabecular and central arteries; these branch and supply the white pulp (white pulp follows arteries). As they exit white pulp, they divide into arterioles and end, dumping all contents of the blood into the red pulp
• blood leaves the spleen by filtering through tiny holes (3micro-m) int he walls of venous sinusoids. Cells that are too old are not flexible enough to fit through these tiny openings, and will be retained in the spleen for destruction. Sinusoids drain into trabecular veins and out form the splenic vein
• red pulp is composed of splenic cords, a framework for the formed elements of the blood supported by mesenchymal reticular cells and their fibers. Interspersed between the cords are splenic sinusoids, the site where cells must reenter to return to circulation

Question 25

What are some causes of splenomegaly?

Answer 25

• red pulp: leukemia (increased WBC production that decreases production of RBCs), hemolytic anemias, metastasized cancer
• white pulp: blood-borne infection (of the spleen), lymphoma
• extra-splenic: problem in liver that backs up to spleen, possibly congestive heart failure