Functional Lymphoid Anatomy

Question 1

Describe the differing roles of central lymphoid tissue vs peripheral lymphoid tissue.

Answer 1

Central lymphoid tissue generates B & T cells, peripheral lymphoid tissue primes them into effector cells

Question 2

Define lymphoid organs.

Answer 2

organized aggregates of lymphocytes in a framework of non-lymphoid cells.

Question 3

What takes place/originates in the bone marrow?

Answer 3

Bone Marrow: B cells

1. Bone Marrow: Lymphocytes derive from hematopoietic stem cells in the bone marrow
   a) Both B & T cells originate here
   b) B cells mature in the bone marrow
   c) B cells are continually produced from the bone marrow, even in adults

Question 4

What are stromal cells?

Answer 4

provide signals that direct the developmental program of the progenitor cells & eventually b-cells

Question 5

Where does the final stages of development of immature B cells into mature B cells occur?

Answer 5

The final stages of development of immature B cells into mature B cells occur in the peripheral lymphoid organs

Question 6

Describe central tolerance.

Answer 6

Central Tolerance: immature B cells in the BM are tested for reactivity to self antigens, or autoreactivity, and are eliminated if autoreactive.

a) 98% of the thymocytes that develop in the thymus also die in the thymus by apoptosis
b) Positive Selection: If the double positive T cell does recognize self-peptide:self-MHC complexes, then it will drop one of the co-receptors & become either CD3(+)CD4(+) or CD3(+)CD8(+) single positive T cells, & migrate to the medulla
c) Negative Selection: If the single positive T cell recognizes self-peptide:self-MHC too strongly, then it will undergo apoptosis. If it does not, it will be exported from the thymus to the periphery

Question 7

How do immature B cells leave the bone marrow? Where do they go?

Answer 7

Immature B cells that have no strong reactivity to self are allowed to mature. They leave the marrow via sinusoids that enter the central sinus and are carried by the venous blood supply to the spleen.

Question 8

Describe the formation of T cells. Where does this take place?

Answer 8

Progenitor cells migrate to the thymus during embryonic development, become thymocytes & mature into T cells

a) Progenitors from the bone marrow enter at the corticomedullary junction & migrate to the outer cortex
b) In the outer cortex/subcapsular region of the thymus, large immature double-negative thymocytes proliferate vigorously
c) Double Negative cells: earliest thymocytes lack the T cell receptor complex (CD3) or T cell co-receptors (CD4 or CD8)
d) From there, T cells migrate deeper into the cortex & undergo receptor rearrangement until they become CD3(+) & CD4(+)CD8(+) double-positive thymocytes
e) If the double positive T cell cannot recognize self-peptide:self-MHC complexes at all, they will undergo apoptosis (a functional T cell has to be able to recognize MHC)

Question 9

How do T cell numbers change in a mature adult?

Answer 9

The development of new T cells in the thymus slows down in mature individuals

T cell numbers are maintained through long-lived individual T cells, as well as division of mature T cells outside the central lymphoid organs

Question 10

Where is the thymus anatomically located?

Answer 10

Located in the upper anterior thorax, just above the heart; consists of numerous lobules

Question 11

Describe the thymic cortex. What type of cells are contained here? What type of development occurs here?

Answer 11

Thymic Cortex: the outer cortical region; contains only immature thymocytes & scattered macrophages; most T cell development occurs here

Question 12

Where do T cell progenitors enter?

Answer 12

Corticomedullary junction: where the T cell progenitors enter

Question 13

Describe the medulla.

Answer 13

Medulla: the inner region; more mature, single-positive thymocytes along with dendritic cells & macrophages

Question 14

What is the thymic cortical stroma?

Answer 14

Thymic cortical stroma: network of epithelia where the T cell precursors reside; provides unique microenvironment for T cell development (like B cell stromal cells); has epithelial cells with long branching processes that express both MHC II & MHC I molecules on their surface

Question 15

Describe how many antigens lymphocytes can recognize.

Where do B and T cells circulate?

When does adaptive immunity occur?

Answer 15

1. Each lymphocyte recognizes only 1 type of antigen, & if it proliferates, all subsequent lymphocytes will be a clone of the first one.
2. B & T cells circulate through the peripheral lymphoid tissues
3. Adaptive immunity occurs if the lymphocyte meets its corresponding antigen in the peripheral lymphoid tissue.

Question 16

Describe the peripheral (secondary lymphoid tissue.

What is it composed of? What type of cells/what do those cells do?

What circulates through this tissue?

What is included within this tissue?

Answer 16

1. Composed of aggregations of lymphocytes in a framework of non-leukocyte stromal cells, which provide the basic structural organization of the tissue & provide survival signals to help sustain the life of the lymphocytes.
2. Mature, naïve lymphocytes are continually recirculating through these tissues, to which pathogen antigens are carried from sites of infection
3. Mature, naïve lymphocytes are maintained & adaptive immune responses are initiated.
4. Lymph nodes
5. Spleen
6. Mucosal Associated Lymphoid Tissue (MALT)

Question 17

Describe some basic principles/functions of the peripheral lymphoid tissues:

What takes place here/what kind of immune response is induced?

How are these tissues dynamic?

What mediating “homing” of lymphocytes to specific regions of peripheral lymphoid tissues?

Answer 17

1. Trap antigens & APCs, enable them to present to migrating lymphocytes
2. Induce adaptive immune responses
3. Provide sustaining signals to lymphocytes that do not encounter their specific antigen immediately so that they survive and continue to recirculate
4. Dynamic tissues: eg- B cell follicles of a lymph node will expand during infection to form germinal centers & the entire LN enlarges (swollen “gland”)
5. The homing of lymphocytes & other cells to specific regions of peripheral lymphoid tissues is mediated by chemokines

Question 18

Lymph Node (LN): Convergence point between blood & lymph.

Define lymph.

Define infection.

What does steady state refer to?

What are High endothelial venules (HEV)?

What is located within follicles?

Cortex?

Paracortical area?

Answer 18

1. Lymph: extracellular fluid from tissues
2. Infection: free antigen or antigen on an APC travel from site of infection through the afferent lymphatic vessels into the draining lymph nodes. Antigen-specific lymphocytes are activated. 1 week later, the activated lymphocyte & its clones leave via efferent lymphatic vessel, then to the blood stream via thoracic duct, & back to the site of infection.
3. Steady-state: naïve lymphocytes that do not recognize their antigen leave via the efferent lymphatics and recirculate until they meet their match or die.
4. High Endothelial Venules (HEV): how naïve lymphocytes get into LN; located in the paracortical areas.

Question 19

Lymph Node (LN): Convergence point between blood & lymph

What is located within follicles?

Cortex?

Paracortical area?

Germinal centers?

Answer 19

5. Follicles: where B cells are located in a LN
6. Cortex: outer area of the LN, where the follicles are
7. Paracortical area: aka “deep cortex” where the T cells are diffusely scattered; also where free antigen gets “trapped” on resident DCs & macrophages; also where migrating DC’s bring their antigens. Great meeting spot for T cells & APCs, so T cells can become activated.
8. Activated T cells & Activated B cells get closer to each other so T cells can “help” B cells proliferate
9. Germinal Centers: where activated B cells undergo intense proliferation & differentiation into plasma cells with the help of T helper cells.

Question 20

Where is the spleen located?

How is it connected to lymphatic system?

What does it collect?

What is it involved in?

How is it associated with newly formed lymphocytes?

How do lymphocytes leave the spleen?

What is secondary function of spleen?

Answer 20

1. Organ located just behind the stomach
2. NOT directly connected with the lymphatic system
3. Collects antigen from the blood
4. Involved in immune responses to blood-borne pathogens (not tissues)
5. Newly formed lymphocytes enter the spleen via the blood, exiting first in the marginal sinus, from which they migrate to the appropriate areas of the white pulp
6. Lymphocytes that survive passage through the spleen probably leave via venous sinuses in the red pulp
7. Secondary function of the spleen is disposal of old red blood cells

Question 21

In regards to the spleen, describe the following:

Red pulp
White pulp
Periarteriolar llymphoid sheath (PALS)
Follicles
Marginal Zone
Blood-borne microbes

Answer 21

8. Red Pulp: majority of the spleen; sites of red blood disposal
9. White Pulp: lymphocytes surrounding the arterioles running through the spleen
10. Periarteriolar lymphoid sheath (PALS): sheath of lymphocytes around a central arteriole; mainly T cells
11. Follicles: adjacent to the PALS; contain B cells, may be germinal centers
12. Marginal Zone: surrounds follicle; contains macrophages & resident, non-circulating B cells
13. Blood-borne microbes, soluble antigens, & antigen:antibody complexes are filtered from the blood by macrophages & immature dendritic cells within the marginal zones, then they migrate to T cell areas & activate the T cells

Question 22

What is peripheral tolerance? What is fate of lymphoids that are self reactive and escape to periphery?

Answer 22

Peripheral Tolerance

1. Not all self tissue is expressed in central lymphoid organs in order to generate central tolerance
2. Lymphocytes that are self-reactive that have escaped to the periphery can have several fates: deletion, anergy, or survival

Question 23

What does GALT do?

Describe its features and specialized anatomy.

Answer 23

GALT (Gut): Collect antigen from the epithelial surfaces of the GI tract

a) Tolerance of food antigens
b) Tolerance of commensal microbiota but responsive to rare pathogens
c) Enormous surface area
d) Tonsils (lingual, palatine)
e) Appendix
f) Specialized anatomy: Peyer’s patches, lamina propria, isolated lymphoid follicles: found throughout the intestine

Question 24

Describe Peyer’s patches in small intestine:

Microfold (M cells)
Follicle
Resident DCs
What do B cells produce?

Answer 24

Peyer’s Patches in small intestine

(1) Microfold (M) cells: specialized epithelial cell which directly collects antigen from the lumen
(2) Follicle: large central dome of B cells, surrounded by smaller numbers of T cells
(3) Resident DCs present antigen to T cells
(4) B cells tend to commit to producing IgA

Question 25

Describe the specialized cells/molecules function of GALT (gut):

Intestinal epithelial cells
M cells
Paneth cells
Secretory IgA, IgM 
Dendritic cell subsets

Answer 25

Specialized cells or Molecules function:

(1) Intestinal epithelial cells: mucus secretion
(2) M cells: luminal antigen sampling
(3) Paneth cells: defensin production
(4) Secretory IgA, IgM: neutralization of microbes in the lumen
(5) Dendritic cell subsets: luminal antigen sampling; lamina propria antigen sampling; T cell tolerance induction; effector T cell activation; induction of B cell IgA class switching; imprinting gut-homing phenotypes of B and T cells

Question 26

Describe BALT:

Exposure?
Specialized anatomy?
Specialized cells or molecules function:

Answer 26

BALT (Bronchus)/Respiratory mucosa (sinus, trachea, lungs)

a) Exposure to mix of airborne pathogens and innocuous microbes and particles
b) Specialized anatomy: Tonsils, Adenoids
c) Specialized cells or Molecules function:

(1) Ciliated respiratory epithelial cells: mucus and defensin production and movement of mucus with trapped microbes and particles out of airways
(2) Secretory IgA, IgM, IgG: neutralization of microbes outside epithelial barrier

Others: Urogenital mucosa, lacrimal & salivary glands, mammary tissue