Tissues, Organs, Cell Migration

Question 1

Primary and Secondary Lymphoid Organs

Answer 1

Primary: Bone marrow and thymus

Secondary: Spleen (blood), lymph nodes (specific tissues), and mucosal associated lymphoid tissues (mucosal surfaces)

Question 2

B cell development

Answer 2

Question 3

T cell development

Answer 3

Question 4

Thymus layout

Answer 4

The Pro-T cells reside in the cortex (on the periphery)

After they begin to express TCRs, they move into the medulla (the center)

Question 5

Hassal’s corpuscles

Answer 5

Reside within the medulla of the thymus. Eosinophilic-staining, concentric layers of epithelial cells. This is where AIRE is expressed and T-cell seletion takes place.

Question 6

Rag enzymes

Answer 6

“Recombinase activating genes”

Mediate VDJ recombination.

Question 7

Order of magnitude of possible human VDJs within a given genome

Answer 7

~10⁹

This does not account for facilitated mutagenesis.

Question 8

T/B-cell selection

Answer 8

Question 9

pre-antigen receptors have. . .

Answer 9

only a single chain.

Question 10

Lymph node structure

Answer 10

Question 11

Lymphadenopathy

Answer 11

Lymphadenopathy most frequently occurs when an immune response is taking place in a node that drains a site of infection. This is because lymphocytes proliferate and more lymph drains into the node.

Another clinically important cause of lymphadenopathy is cancer of lymphocytes (lymphoma) or cancer from other tissue that has spread (metastasized) via lymph to the node.

Question 12

Lymph node histology

Answer 12

Question 13

Germinal Center

Answer 13

Contain activated B cells, plus other cells types.

Germinal centers form during an active B cell immune response to protein antigens. In order for germinal centers to form, antigen‐ activated B cells also must get signals from helper T cells.

If a pathologist sees germinal centers in a lymph node biopsy, she/he would inform the clinical team that this is a “reactive” node.

Question 14

High endothelial venules

Answer 14

Present only in secondary lymphoid organs, named for the characteristically tall appearance of their endothelial cells.

These HEV, located in the T cells zone, are the sites where naïve T and B cells leave the circulation and enter the lymph node tissue. There are adhesion molecules on naïve lymphocytes that bind to adhesion molecules on the HEV which mediate the lymphocyte migration out of these HEV. Naive lymphocytes will not migrate out of the post‐capillary vessels in most other tissues, which are not HEVs.

Question 15

How do the B cells get to the follicles, while the T cells stay in the T cell zone?

Answer 15

Chemokines!

Question 16

Spleen

Answer 16

The red pulp is composed vascular channels called sinusoids, connected directly downstream to branches of the splenic artery. The sinusoids are lined by macrophages.

Question 17

Structure of splenic white pulp

Answer 17

Question 18

Marginal zone

Answer 18

Located in the margins of the white and red pulp of the spleen.

The B cells in the marginal zone (marginal zone B cells, MZB) are different from those in the follicles (follicular B cells); MZBs do not interact so much with T cells, and the antibodies they produce are less diverse than those produced by B cells in the germinal centers.

Question 19

Mucosal associated lymphoid tissues

Answer 19

Organized, but not encapsulated, collections of lymphocytes, antigen presenting cells and supporting vascular and conduit structures similar to those found in lymph nodes.

They have T and B cell zones like regular lymph nodes, but have overall a higher B to T cell ratio.

Unlike lymph nodes, they are not downstream of lymphatics and do not have feeding vascular sinusoids.

Examples: Tosils, aneloids, Peyer’s patches, lymphoid aggregates in SI/colon/bronchial mucosa.

Question 20

Peyer’s Patches

Answer 20

The PP in the yellow box is interfacing with the epihelia with the aid of dendritic cells and M cells.

Question 21

How antigens reach Peyer’s patches from the lumen

Answer 21

Question 22

M cells

Answer 22

Take up antigens, even whole microbes, at the lumenal surface, place them into membrane bound vesicles, and transport them (transcytose) to the ablumenal surface, at the edge of the PP, where they are handed over to antigen presenting cells that can display the antigens to lymphocytes.

Question 23

Mesenteric lymph nodes

Answer 23

Located in the connective tissue sheets that are attached to the bowel wall. Supplied with lymph draining from the vacsulation of the lamina propria, as opposed to peyer’s patches with interact with the lumenal compartment.

May also serve as a site of initiation of adaptive response for mucosal challenges, as lamina propria dendritic cells may migrate to a peyer’s patch or a mesenteric lymph node.

Question 24

Lymphocytes that are activated and differentiate into effector cells in MALT structures . . .

Answer 24

express combinations of adhesion molecules and chemokine receptors that allow them to preferentially home back to the subepithelial tissues of the same mucosa

Question 25

Route of immune cell migration

Answer 25

Question 26

Naive T-cell SLO Homing in Infection

Answer 26

Question 27

CCR7

Answer 27

Chemokine receptor which binds CCL19 and 21, which are expressed in the T-cell zone near the high endothelial venule.

Expressed by both Naive T-cells and Dendritic Cells, to facilitate antigen presentation. Once activated, Naive T-cells lose CCR7 expression.

Some memory T-cells also express CCR7 until reactivated.

Question 28

Naive B-cell SLO homing in infection

Answer 28

Plasmablasts activated in the SLOs home to the bone marrow to mature into full plasma cells.

Question 29

Enlarged tonsils cannot be. . .

Answer 29

Enlarged tonsils cannot be palpated externally.

Question 30

Monocytes live ____ in the blood

Answer 30

Monocytes live 5-8 days in the blood

Question 31

~1 week post-irradiation/chemotherapy

Answer 31

increased susceptibility to infection (neutrophils) and increased bruising/bleeding tendency (platelets reduced by ~half, but clotting already substantially affected)

Question 32

Splenectomy predisposes to. . .

Answer 32

Splenectomy predisposes to infection by encapsulated bacteria (like S. pneumoniae).

Question 33

Autosplenectomy

Answer 33

Necrosis of the spleen due to ischemia and infarction (ischemia-induced necrosis of any type).

May occur in sickle cell anemia due to sickle cell crisis of the spleen. This is common enough that many sickle cell patients are on prophylactic antibiotics.

Question 34

Follicular DCs are. . .

Answer 34

Follicular DCs are not from bone marrow.

Question 35

Immune cells enter tissues via ____.

Answer 35

Immune cells enter tissues via venules only.

Only venules express adhesion molecules.

Question 36

T follicular helpers

Answer 36

T follicular helpers stay in the lymph node upon activation and move to the follicles to stimulate B cells.