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Host Defense Exam 1 > Functional Lymphoid Anatomy > Flashcards

Functional Lymphoid Anatomy Flashcards

1
Q

What is the purpose of lymphoid tissue?

A
  • lymphopoiesis
  • development of antigen-specific lymphocytes
  • central and peripheral tolerance
  • sustaining signals to maintain lymphocyte levels
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2
Q

Differentiate between central and peripheral tissues: types.

A
  • central = bone marrow & thymus

- peripheral = spleen, lymph nodes, mucosal (MALT), cutaneous, etc.

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3
Q

What is the function of central lymphoid tissue?

A

lymphopoiesis of both B and T cells, central tolerance

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4
Q

Generally describe T cell development (locations).

A
  • made in bone marrow as immature thymocyte
  • travel to thymus during fetal development
  • becomes naive T cell
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5
Q

Define central tolerance.

A

make sure they aren’t self-reactive

  • positive selection (for T cells): in the cortex of the thymus, double positive thymocytes bind to a particular MHC molecule and are selected for CD4 or CD8
  • negative selection (for T cells): in the medulla, single-positive thymocytes are exposed to self peptides produced by medullary epithelial cells. Those that bind undergo apoptosis
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6
Q

What are the functions of peripheral lymphoid tissue?

A

facilitate antigen-lymphocyte interactions, peripheral tolerance, supports survival of circulating lymphocytes, activation of naive lymphocytes

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7
Q

Describe the lineage development of B and T lymphocytes in the bone marrow.

A

HSCs => granulocytes => myeloid or lymphoid
lymphoid => B and T cell precursors
- T cells travel to thymus, B cells remain in bone marrow
=> spleen => other organs

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8
Q

What is the function of stromal cells?

A

secrete chemokines that provide the microenvironment for lymphocyte development and central tolerance in the central lymphoid tissue.
- peripheral tissues also have stroma-like cells

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9
Q

Describe how the B cells move in the bone marrow as they develop.

A
  • begin at the endosteum, below the inner cavity of long bones
  • as they begin to develop, they move toward the stromal cells in the trabeculae (propelled by surface maturation markers)
  • as they mature, they move toward the central sinus of the marrow cavity => circulation
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10
Q

Describe the fate of central tolerance selection in the bone marrow.

A
  1. If a B cell doesn’t react to self-peptide, it is free to go into circulation
  2. If a B cell reacts to a multivalent self molecule, it will either undergo apoptosis or receptor editing to change its antigen specificity
  3. If the B cell is still reacting to the self, it will undergo apoptosis or become anergic
  4. clonal ignorance
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11
Q

Define clonal ignorance.

A

A B cell might be designed to attack a self-antigen. But that particular antigen may not be found in the bone marrow (or present in very low concentrations) => the bone marrow doesn’t know that this cell is autoreactive and allows it to go to the peripheral tissue.
(possible theory to explain autoimmunity)

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12
Q

List common lymphoid tissue structures. Which are only found in peripheral lymphoid tissue?

A
  • capsule
  • subcapsular region
  • cortex
  • corticmedullary junction
  • medulla
  • trabeculae
  • stroma (non-lymphoid)
  • parenchyma (lymphoid)
  • follicles and germinal centers (only periphery)
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13
Q

What kind of leukocytes make up parenchymal cells in the lymphoid tissues?

A
  • lymphocytes
  • macrophages
  • dendritic cells
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14
Q

Describe the spread of parenchyma in the thymus.

A
  • cortex = immature thymocytes and few macrophages

- medulla = mature thymocytes, most macrophages and DCs

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15
Q

What happens if you don’t have a thymus? What is a disease associated with this in children?

A
  • can’t make mature T cells

- DiGeorge’s Syndrome (chromosomal deletion)

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16
Q

Which lymphocyte production rate is affected with age?

A

T cell proliferation declines with age, but numbers are maintained

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17
Q

What do cortical epithelial cells in the thymus secrete? What do medullary epithelial cells in the thymus secrete?

A

cortical - IL-7

medullary - growth factors and cytokines

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18
Q

List the mechanism for T Cell development.

A
  1. T cell precursors enter the thymus at the CMJ and migrate upward into the cortex, where they are acted on by cortical epithelial cells.
  2. At this stage, T cells are double-negative (CD3-, CD4-, CD8-) and have a beta chain with a placeholder alpha chain.
  3. Once they migrate to the deep cortex and subcapsular region, they undergo receptor rearrangement and express CD3. The cells become double-positive (CD3+, CD4+, CD8+)
  4. Cortical epithelial cells express MHC Class I and II. Only those thymocytes that have some affinity for these molecules will continue to the CMJ/medulla. If they do not bind or bind too strongly, they undergo apoptosis. Depending on which MHC molecule that cell is bound to determines its cofactor expression. Now the cells are single positive (CD3+CD4+ or CD3+CD8+)
  5. In the CMJ and medulla, medullary epithelial cells express and produce peptides found all over the body. These peptides are bound to MHC on APCs. T cells that bind to these self-peptides undergo apoptosis
  6. Only those T cells that are single positive and not self-reactive are allowed to leave
19
Q

How do lymphocytes enter/exit the peripheral lymphoid tissue?

A
  • enter via artery (brought by chemokines)
  • go to the paracortical areas
  • exit into the paracortical areas via high endothelial venules (HEVs)
  • naive B cells form primary lymphoid follicles in the paracortical areas (remain as long as they get support signals)
  • exit via efferent lymphatics
20
Q

How do antigens enter/exit the peripheral lymphoid tissue?

A
  • enter as free floating antigens or attached to APCs in the afferent lymphatics (brought by chemokines)
21
Q

Which lymphocyte is predominantly found in the paracortical area?

A

T cells

22
Q

Describe antigen-lymphocyte interaction in the peripheral lymphoid tissue.

A
  1. chemokines => APCs present to B cells in the follicles => activated B cells
  2. chemokines => APCs present to helper T cells (CD4+) in the paracortical area (T cell zone) => activated helper T cell
  3. chemokines bring the B cells and T cells closer => interaction
  4. B cell proliferation and differentiation
23
Q

What are possible fates of B cells once B-T interaction has occurred in the lymphoid tissue?

A
  1. long-lived plasmoblast (?) go back to bone marrow and become a plasma cell
  2. hypermutate and become more specific (germinal center)
  3. short-lived plasmoblast stay in the medulla to create rudimentary/quick antigen response to begin immune response
  4. memory B cells migrate to the bone marrow
24
Q

What is occurring in a secondary follicle?

A
  1. activated B cells in the extrafollicular area enter the follicle again
  2. proliferation of activated B cells (germinal center)
  3. hypermutation and affinity maturation of B cells => more specific (facilitated by follicular DCs)
  4. secretion of plasma cells and memory B cells
25
Q

Are there T cells in the follicles?

A

yes, allowed to give signaling for proliferation (germinal center)

26
Q

How are free antigens presented?

A
  1. enter via lymphatic afferents, travel in subcapsular region
  2. small antigens travel down conduits to the follicles to be picked up by follicular dendritic cells
  3. larger antigens bind to specialized subcapsular macrophages that preserve them to transfer to follicular DCs or directly to B cells
27
Q

List functions of the spleen.

A
  • immune responses to blood-borne encapsulated pathogens (meningococci, pneumococci)
  • RBC disposal and iron recycling
  • secondary hematopoiesis if needed
28
Q

Differentiate between medullary cords and sinuses in the spleen.

A

medullary cords = short lived plasma cells making antibody

sinus = long lived plasmoblasts on their way to bone marrow to become long lived plasma cells

29
Q

How do lymphocytes enter/exit from the spleen? antigens?

A

lymphocytes

  • enter via blood
  • exit via splenic vein to the site of infection

antigens

  • enter via blood
  • exit
30
Q

What can be expected to people with impaired splenic function?

A

reduced immunity

predisposition to encapsulated pathogen invasion

31
Q

Define splenic red pulp.

A
  • site of RBC disposal
  • surrounded by macrophages that filter out RBCs, opsonized cells, and microbes
  • sinusoids - where blood flows in
32
Q

How does systemic infection affect iron?

A

=> anemia

  • RBCs pick up antigens in the blood
  • in the spleen, macrophages see those antigens and engulf the RBC-antigen complex from the blood in the spleen
33
Q

Define splenic white pulp.

A
  • collections of densely packed lymphocytes surrounding arterioles in the spleen
  • organized around central arterioles which drain into marginal sinus
  • marginal zone = specialized B cells and macrophages
34
Q

Define PALS.

A

PeriArteriolar Lymphocytic Sheath

- T cell zone surrounding central arteriole in spleen

35
Q

Describe the branching of the trabecular artery.

A

trabecular artery => central arteriole (surrounded by PALS) => follicular arteriole (to the marginal sinus)

36
Q

Define MALT.

A

mucosal associated lymphoid tissue

- gut, respiratory, tonsils, etc.

37
Q

Where are lymphocytes found in GALT?

A 
intraepithelial lymphocytes (more cytotoxic)
lamina propria lymphocytes
38
Q

What is the function of the crypts in GALT?

A

secreted defensin

39
Q

What is the Peyer’s Patch?

A

tissue over the lymphoid tissue in the gut

  • no capsule
  • take in antigens from the lumen (blood and lymph independent entry)
40
Q

What are microfold cells?

A

M cells

- transcellular transport of antigens from lumen into the lymphoid tissue to interact with APCs

41
Q

What does salmonella do to GALT?

A
  • takes over M cells
  • causes M cells to die
  • leaves giant hole in intestinal wall and causes invasion
42
Q

What is the result of lymphocyte activation in GALT?

A

plasmoblast secretes IgA => mucosa

43
Q

What other cell is involved in luminal sampling in GALT?

A

dendritic cells

Host Defense Exam 1 (12 decks)

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