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HD Exam 1 > Lecture 9, Fcnal Lymphoid Anatomy > Flashcards

Lecture 9, Fcnal Lymphoid Anatomy Flashcards

1
Q

Name 4 purposes of having lymphoid tissue.

A
  • Supports lymphopoiesis
  • Supports development of incredibly diverse repertoire of ag-specific lymphocytes
  • Critically important for central & peripheral tolerance
  • Provides sustaining signals for lymphocyte survival
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2
Q

What places in the body have central lymphoid tissue?

A

Bone marrow, thymus

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3
Q

What places in the body have peripheral lymphoid tissue?

A
  • Lymph nodes
  • Spleen
  • Mucosal associated lymphoid tissue (MALT)
  • Cutaneous system
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4
Q

What are two main processes that the central lymphoid tissue is responsible for?

A
  • Central tolerance

- Lymphopoiesis

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5
Q

Where are B cells initially made?

Where are T cells initially made?

A
  • Bone marrow

- Bone marrow (T cell progenitors migrate to *thymus during embryogenesis and develop there)

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6
Q

Naive lymphocytes enter the LN from (blood/lymphatics)?

A

Blood

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7
Q

Naive lymphocytes are activated in the (central/peripheral) lymph tissue.

A

Peripheral

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8
Q

___________ tolerance occurs in central lymphoid tissue, ___________ tolerance occurs in peripheral lymphoid tissue.

A
  • Central

- Peripheral

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9
Q

During B cell lymphogenesis, early stem cells hang out at the ____________, just below the inner cavity of the long bones, but then move toward the _________ cells in the trabeculae.

A
  • Endosteum

- Stromal

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10
Q

During B cell lymphogenesis, progression of B cell development depends on _________________ provided by the stromal cells.
(general answer)

A

Maturation factors

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11
Q

During B cell lymphogenesis, as B cells mature, they conveniently move from the endosteum toward the _______________ of the marrow cavity, then into circulation, bound for the _________________________.

A
  • Central sinus

- Peripheral lymphoid organs

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12
Q

*Are T cells continually produced throughout adult life?

Are B cells?

A
  • T cells: Yes, but T-cell #s are maintained thru long-lived individual T cells together w/ the division of mature T cells outside the central lymphoid organs.
  • B cells: Yes, even adults continually produce them in the marrow
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13
Q

If a B cell survives central tolerance in the marrow and ends up meeting an antigenic match in a peripheral lymphoid organ, it will mature into one of these 2 types of cells:

A
  • Plasma cell (secretes AB’s)

- Memory B cell

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14
Q

Regarding central tolerance, what happens if an immature B cell does not react to self?

A

Migrates to periphery (probably becomes a mature B cell)

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15
Q

Regarding central tolerance, what happens if an immature B cell reacts to a multivalent self molecule?

A
  1. Clonal deletion -> apoptosis (in marrow)

2. Receptor editing -> if it works, migrates to periphery

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16
Q

Regarding central tolerance, what happens if an immature B cell reacts to soluble self molecules?

A

Migrates to periphery and becomes anergic

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17
Q

*Regarding central tolerance, what happens if an immature B cell binds w/low affinity to a non-cross-linking self molecule?

A

Migrates to periphery and becomes a clonally ignorant mature B cell (potentially leading to autoreactive plasma cells in presence of lots of large quantity of self)

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18
Q

What are the 3 parts of lymphoid tissue you’d see throughout all lymphoid tissue except the MALT?

A

Capsule, subcapsular area, trabeculae

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19
Q

Explain how trabecula are associated w/the capsule and what parts of the LN they separate.

A

Trabecula extended from capsule and separate cortex into superficial outer cortex with follicles and an inner paracortex or deep cortex. An inner medulla leads to a hilus where blood vessels and the efferent lymphatic is found.

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20
Q

What are the 3 parts of lymphoid tissue you’d see throughout all lymphoid tissue except the spleen or MALT?

A

Cortex, corticomedullar junction, medulla

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21
Q

What types of cells are stroma?

A

Non-leukocytes

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22
Q

What types of cells are parenchyma?

A

Leukocytes

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23
Q

What are 2 major LN regions that you’d find in the periphery but not in central lymphoid tissue?

A
  • Germinal centers
  • Lymphoid follicles
    (Germinal centers are w/in the follicles)
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24
Q

Name the 2 major regions w/in the thymus, and what subregion divides them.

A

Cortex, corticomedullar junction, medulla (not found in spleen or MALT)

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25
Q

Besides cortical epithelial cells, what 2 immunological cell types would you find in the cortex of the thymus?
Which would there be more of?

A
  • Immature thymocytes (mostly)

- Scattered macrophages (few)

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26
Q

What 3 cell types would you find in the medulla of the thymus?

A
  • Thymocytes
  • DCs
  • Macrophages
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27
Q

If you had HSCs that form T cell progenitors in the marrow, but you’re athymic, can T cells still develop?

A

No, need thymus

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28
Q

What happens to the vast majority (98%) of thymocytes during development in the thymus?

A

They die by apoptosis and are removed by cortical macrophages

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29
Q

Thymocytes depend on the thymic ______________ cells for survival.

A

Epithelial (the cytokines produced, etc.)

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30
Q

When does the thymus finish development?
When is rate of T cell production greatest?
When does the rate of T cell production begin to decelerate?
When does T cell production cease?

A
  • Before birth
  • Before puberty
  • After puberty
  • Never (except death, dz)
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31
Q
  • *Explain the phases of T cell development, in terms of CD markers. (5 main phases)
  • Include when the 2 phases of chain rearrangement occur.
  • Note: progression of T cell development in the thymus is dependent on timely expression of various surface and signaling molecules.
A
  1. Start as triple negative (CD3-, CD4-, CD8-)
  2. Further interaction w/thymic stromal cells, now double negative (CD3+, CD4-, CD8-); mostly alpha-beta (vs. gamma-delta) - Beta-chain rearrangement occurs (while double negative)
  3. Surface markers expressed, now double positive (CD3+, CD4+, CD8+) - Alpha-chain rearrangement occurs (while double positive)
  4. 5% become single positive, export to periphery
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32
Q

During T cell lymphopoeisis, in addition to receptor maturation, the double positive, then single positive T-cells are undergoing _________ and __________ selection.

A

Positive and negative (central tolerance)

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33
Q

**Explain the pathway of T cells as they mature while in the thymus. (3 main steps)

A
  1. Enter via HEV at medulla (double negative)
  2. Migrate to cortex, encounter epithelial cell (become double positive)
  3. Return to medulla, encounter DC or macrophages, thus becoming single positive
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34
Q

During T cell central tolerance, thymic cortical epithelial cells express _________ peptide in MHC I or MHC II molecules.

A

Self

35
Q

During T cell central tolerance, does positive or negative selection come first?

A

Positive selection

36
Q

*During T cell central tolerance, what occurs during positive selection?
What surface marker(s) will selected cells express?
Where will the cells migrate to, if selected?

A

Double positive thymocytes with affinity for peptide:MHC complex (of the epithelial cells or medullary DCs/macrophages) will survive as either CD4+ or CD8+ single positive thymocytes and migrate to medulla.

37
Q

*During T cell central tolerance, what occurs during negative selection?

A

After positive selection, CD4+ or CD8+ T cells with too high affinity for peptide:MHC complex (of cortical thymic epithelial cells or medullary DCs/macrophages) are deleted; otherwise migrate to periphery.

38
Q

How long does it take for an adaptive immune response to an antigen that has not been encountered before does to become effective?

A
  • More than 4-6 days (so about 1 week)
39
Q

When an infection occurs in a tissue such as the skin, free ag and ag-bearing DCs travel from the site of infection thru the _________________ into the draining LNs, where they activate antigen-specific lymphocytes.

A

Afferent lymphatic vessels

40
Q

The activated lymphocytes in the LN undergo a period of proliferation and differentiation, after which most leave the lymph nodes as effector cells via the ______________________.

A

Efferent lymphatic vessel

41
Q

Naive lymphocytes that do not recognize their antigen leave the LN thru the ____________________ and are returned to the blood, from which they continue to recirculate through lymphoid tissues until they recognize antigen or die.

A

Efferent lymphatic vessel

42
Q

In LNs, lymphocytes enter from ______________________, which are located within the T-cell zones.

A

High endothelial venules (HEVs)

43
Q

*Lymphocytes squeeze out of the vessels through HEVs into the __________________.

A

Paracortical areas (b/w medulla and cortex)

44
Q

Naive B cells migrate through the HEVs (to enter the LN) in the paracortical area (*mostly T cells) and come to rest in the ____________ where, unless they encounter their specific antigen and become activated, they remain for about (how long?)

A

Follicle

- a day

45
Q

The precise location of B cells, T cells, macrophages, and DCs in peripheral lymphoid tissue is controlled by______________, which are produced by both stromal cells and bone marrow derived cells.

A

Chemokines

46
Q

When a freely floating or APC-digested Ag enters the LN via the afferent lymphatics, they are brought into the ____________________.

A

Paracortical area (mostly T cells, to which the Ag is displayed)

47
Q

After the T cells in the paracortical areas interact w/free-floating or APC-digested Ag and become activated, what happens next?

A

B cells migrate to the T cells from the follicle via chemokines (they migrate towards each other, actually)

48
Q

What part of the LN contains the follicles?

A

Cortex

49
Q

Prior to interacting w/T cells, how do B cells in the follicle become exposed to Ag’s? (2 ways)

A
  • Free ag can travel to the follicles via conduits

- Ag can be captured by LN macrophages/resident medullary DCs

50
Q

Free ag on LN macrophages or DCs can be presented directly to follicular _____________ or passed to follicular ____________.

A
  • B cells

- DCs

51
Q

Explain the general steps of lymphocyte activation towards becoming plasma cells in the LN once all cells and ag are already in the LN.
What happens to extrafollicular B cells?
Follicular B cells?

A
  1. B cells & CD4+ T cells recognize ag
  2. Activated lymphocytes migrate toward each other
  3. Results in B cells proliferation/differentiation
  4. Extrafollicular B cells re-stimulated by extrafollicular T cells to form short-lived plasma cells
  5. Follicular B cells undergo somatic hypermutation & affinity maturation, switching & formation of long-lived plasma cells & memory B cells
52
Q

Once B cells are activated they migrate to a ________________ and start to ________________.

A
  • germinal center

- proliferate

53
Q

During/after B cells proliferate in the germinal centers, what processes do they undergo?

A

Somatic mutation, affinity maturation, isotype switching. (in the follicle)

54
Q

Long-lived plasmablasts in medullary sinus go to ______________ or ______________ to become long-lived plasma cell.

A

Bone marrow or gut

55
Q

What occurs in the white pulp of the spleen?

A

Immune responses to blood-borne pathogens

56
Q

What occurs in the red pulp of the spleen?

A

RBC Disposal & Iron recycling

57
Q

Besides forming immune responses to blood-born pathogens, RBC disposal, and Fe3+ recycling, what other function can the spleen perform, if necessary?

A

(Secondary) Hematopoiesis

58
Q

*What type of organisms is the spleen especially good at clearing?

A

Encapsulated bacteria: Pneumococci, Meningococci

59
Q

Do ag enter the spleen via lymphatics or blood?

A

Blood (there are no lymphatics to spleen)

- Via splenic a.

60
Q

*After blood enters the spleen via the splenic a, some arteriolar branches end in vascular _____________ lined by ______________ which filter out RBCs & opsonized cells & microbes

A
  • Sinusoids

- Macrophages

61
Q

The splenic white pulp is a collection of densely packed _____________.

A

Lymphocytes

lymphocytes surrounding the arterioles running through the spleen

62
Q

The architecture of the spleen is similar to ____________.

A

LNs

63
Q

Explain the blood drainage pattern of the spleen’s white pulp.

A

Organized around central arterioles which drain into the marginal sinus

64
Q

*What types of cells are contained in the marginal zone of the spleen (to which the central arterioles drain)?
What types of cells surround the central arterioles?

A
  • B cells (+ macrophages)
  • T cells (mostly)

(like in LN, ag from blood encounters T cells at HEV, then B cells)

65
Q

What are the 2 cells that can sample ag from the marginal sinus of the spleen?

A
  • Circulating DCs

- Sampling by marginal zone macrophages

66
Q

In 1 general sentence, explain what is occurring w/ peripheral tolerance.

A

In the absence of an infection, mature B & T cells that encounter a strongly cross-linking antigen in the peripheral lymphoid organs will undergo clonal deletion or anergy.

67
Q

What happens to a B cell if it fails to reach a primary follicle?

A

Appears to die after several days (there is a competition amongst B cells to enter follicle)

68
Q

There is a continual positive selection of T cells in the periphery by…

A

Repeated contacts with self-peptide:self-MHC

69
Q

What is MALT?

*Where are areas where you’d find it?

A

Mucosal associated lymphoid tissue

  • Gastrointestinal tract, the upper and lower respiratory tract & the urogenital tract
  • Also includes the exocrine glands associated w/ these organs, such as the conjunctivae and lachrymal glands, salivary glands, and lactating breast
70
Q

Besides organized lymphoid tissues in MALT, there are also scattered areas of lymphoid tissue. What types of cells might you find in areas of scattered lymphoid tissues?

A
  • Intraepithelial lymphocyte (tend to be toxic)
  • Lamina propria lymphocyte (tend to be helper)
  • Defensins produced in the crypts
71
Q

What’s the main e.g. of organized lymphoid tissue in the gut?

A

Peyer’s patches

72
Q

How are Peyer’s patches different from regular LNs?
Are they encapsulated?
Do they have follicles/germinal centers?

A
  • They are NOT encapsulated
  • Have lymph and blood-independent entry of antigen from the lumen
    (they do have follicles w/germinal centers, tho–IgA)
73
Q

What are the 2 main ways Ag enters Peyer’s patches?

A
  1. M cells- transcellular xport of various substances from the intestinal lumen across the epithelial barrier to underlying APCs
  2. Lamina propria DCs (extend their arms paracellularly or str8 paracellular)
74
Q

*The most abundant immunoglobulin in MALT tissues is Ig__ (predominant) secreted by plasmablast which circulate back to the mucosal tissue after activation
(Exception: genitourinary Ig_ )

A

IgA

IgG

75
Q

How is the spleen directly connected w/the lymphatic system?

A

It is not!

76
Q

Newly formed lymphocytes enter the spleen via the blood, exiting first in the __________________, from which they migrate to the appropriate areas of the white pulp.

A

Marginal sinus

77
Q

Lymphocytes that survive passage through the spleen probably leave via venous sinuses in the ________ pulp.

A

red

78
Q

What is a periarteriolar lymphoid sheath (PALS):

A

In the spleen, sheath of lymphocytes around a central arteriole; mainly T cells

79
Q

B cells of Peyer’s patches tend to commit to producing Ig_.

A

IgA

80
Q

What types of intestinal cells produce defensins?

A

Paneth cells

81
Q

Where do long-lived plasma cells develop?
What are their precursors called?
Where do they then migrate to?

A
  • Germinal centers
  • Plasmablasts
  • Bone marrow
82
Q

What area in the spleen forms the boundary between the red pulp and white pulp?

A

Marginal zone (outside the marginal sinus, which has the B cells and macrophages, and is drained into by the central arteries)

83
Q

*What cells do immature thymocytes encounter to become double positive? (and where?)
Which do they encounter to become single positive? (and where?)

A
  • TECs (cortex)

- Macrophages, DCs, or TECs (medulla)

HD Exam 1 (15 decks)

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