L7: Lymphoid Tissues

Question 1

3 different types of lymphoid tissue? Characteristics of each?

Answer 1

1. ) Primary lymphoid tissue: bone marrow and thymus
   - generation of mature, but antigen naïve T and B cells, development of antigen recognition, where rearrangement of antigen receptor genes occur
2. ) Secondary lymphoid tissue: LNs, tonsils, Peyer’s patches, spleen
   - naïve lymphocyts reside here while waiting for activation, location where antigen funneled to antigen-specific B and T cells to drive activation to effector and memory cells
3. ) Tertiary lymphoid tissue: skin, GI tract, lungs, vagina (any tissue in body that can become infected)
   - where elimination of antigen occurs, battlefield where immune system defends tissues from microbes, these tissues typically have direct contact with external environment

Question 2

Where are B lymphocytes born? Where do they mature?

Answer 2

• Born in bone marrow (located near inner surface of bone), more mature cells reside in central axis of marrow cavity. Immature to mature B cell transition can occur in bone marrow or secondary lymphoid organs

Question 3

Where are T lymphocytes born? Where do they mature?

Answer 3

• Born in bone marrow. Stem cells become prothymocytes in bone marrow.
• Prothymocytes home to thymus via blood, become thymocytes and differentiate into mature T cells in thymus.
• Mature T cells leave thymus and populate secondary lymphoid organs

Question 4

When does thymus atrophy?

Answer 4

• After puberty, “gone” by middle age

Question 5

Subdivisions of thymus. Describe maturation / development of thymocytes across these subdivisions

Answer 5

• Thymic lobules contain cortex and medulla. Cortex serves as entrance of prothymocytes, medulla serves as area of mature T lymphocytes and where they exit to secondary lymphoid organs
• Cortex: double negative cells exist and mature in double positive (CD4 and CD8), undergo positive selection
• Medulla: transition from cortex, becoming CD4 or CD8 cells, can also become Treg CD4 cell. CD4+ and CD8+ cells undergo negative selection. Once mature, can migrate to periphery
• Throughout course of thymocytes through thymus they are exposed to hormones and direct contact with various cell types that leads to selection of cells via positive and negative selection.

Question 6

What are Hassall’s corpuscle?

Answer 6

• Structures in medulla of thymus thought to be thymocyte graveyards

Question 7

What cells are present in the cortex of the thymus other than the thymocytes? Function?

Answer 7

• Cortical epithelial cells are the “nurse cells” for the thymocytes and function in: cell-cell contact, release cytokines and peptide hormone to drive development of thymocytes

Question 8

What immunological organ is responsible/are main responders for blood-borne antigens? Tissue-borne antigens?

Answer 8

• Blood-borne antigens: spleen

- Tissue-borne antigens: lymph nodes

Question 9

In what part of the lymph node do you find the B cell population? T-cell population?

Answer 9

1. ) Cortex within follicles and germinal centers = B-cell population
2. ) Paracortex = TH-cell population

Question 10

Describe structures and cell populations found within the cortex of the lymph node? Within medulla?

Answer 10

• primary follicles are resting B cells
• secondary follicles are antigen-activated B cells
• germinal centers are proliferating B cells
• T helper cells found in paracortex
• DCs in medulla/areas rich in T cells
• Macrophages found in subcapsular/marginal sinuses and medullary cords of lymph nodes

Question 11

Ways in which antigen can be captured within the lymph nodes?

Answer 11

1. ) directly to follicles (B-cells)
2. ) taken up by macrophages in subscapular/marginal sinuses
3. ) taken up by resident DC in medulla
4. ) B cells and Langerhans cells can migrate into lymph node

Question 12

Of all the antigen presenting cells, which is the main stimulator of primary immunity?

Answer 12

• Dendritic cells

Question 13

In terms of the architecture of lymph nodes, what structures would predominate if there was little antigen stimulation?

Answer 13

• few primary follicles would be present, no secondary follicles

Question 14

In terms of the architecture of lymph nodes, what structures would predominate if there was a lot of antigen stimulation?

Answer 14

• numerous secondary follicles

Question 15

What structures within lymph nodes make it possible for lymphocytes to enter lymph nodes from blood?

Answer 15

• High endothelial venules

Question 16

What is the function of B cells percolating through T cell-rich areas in lymph nodes?

Answer 16

• Enhancing probability that an antigen-specific B cell will interact with an antigen-specific T cell, resulting in B and T cell activation

Question 17

Function of spleen?

Answer 17

• Remove particulate matter and senescent RBCs from circulation (in red pulp) and expose lymphocytes to antigens (in white pulp) – main immunologic organ responsible for blood-borne antigens

Question 18

Describe regions of white pulp within spleen. Describe cell populations within each area

Answer 18

• Area surrounding central and penicilliary vessels is the periarteriolar lymphatic sheath (PALS) that is rich in T-cells
• Branch points for arteries / extensions of PALs are areas of follicles that are rich in B cells

Question 19

Describe MALT. Describe cell types and features that participate in maintaining a functioning immunological barrier.

Answer 19

• Intraepithelial lymphocytes are present within the mucosal epithelium. Paneth cells here secrete anti-microbial peptides
• Macrophages, plasma cells (secrete IgA), mast cells, T/B-cells and DCs are present within the lamina propria of the mucosa.
• Peyer’s patches (secondary MALT) refers to regions in the terminal ileum of the small intestine where B cell follicles are surrounded by zones rich in T cells. HEVs transport lymphocytes to Peyer’s patches
• M cells transport proteins and microbes from intestinal lumen to phagocytic cells

Question 20

Tertiary lymphoid tissue. How are immune cells delivered to this tissue? What cells primarily reside here?

Answer 20

• Cells delivered via bloodstream: extravasation of immune cells occurs via similar mechanism to that of neutrophils
• Primary cells here are memory B and T cells

Question 21

Describe “life cycle” of Langerhans cells

Answer 21

1. ) Immature DCs reside in epidermis, extend their processes throughout epidermis, capture antigen
2. ) Under proinflammatory cytokines, retract their processes, lose adhesiveness and migrate into lymphatic channels
3. ) Transport antigen to nearest lymph node and present and activate T cells
4. ) Once in lymph node, they are mature and can no longer ingest antigen

Question 22

Describe immune response in a lymph node

Answer 22

1. ) B-cell interacts with an antigen specific T cell (that may or may not have interacted with DC)
2. ) B-cell is activated, proliferates and differentiates (into plasmablast)
3. ) Some plasmablasts migrate into medullary cords and produce low affinity antibody (short-lived plasma cells)
4. ) Other plasmablasts migrate to B-cell rich areas to form germinal centers where they divide every 6-8 hours. The differentiate here into plasma cells secreting high affinity antibody that is picked up by lymph and dumped into bloodstream. Most plasma cells travel to bone marrow (major site of antibody production). Some B and T cells become memory cells

Question 23

What are addressins?

Answer 23

• These are molecular tags on lymphocytes that allow them to be located in specific lymphoid organs/tissues

Question 24

What is lymphoid recirculation?

Answer 24

• Lymphocytes travel between lymphoid organs and do not stagnate in one location
• This is critical for dispersal of naïve and memory cell populations

Question 25

Where are memory lymphocytes primarily located? Naïve lymphocytes?

Answer 25

• Memory lymphocytes are primarily located in the peripheral blood
• Naïve lymphocytes are primarily located in secondary lymphoid organs where they have higher chance of interacting with antigen