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Innate Immunity > Haematopoiesis and Lymphorganogenesis > Flashcards

Haematopoiesis and Lymphorganogenesis Flashcards

1
Q

What is hematopoiesis?

A

Hematopoiesis is the process of blood cell formation.

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2
Q

Where do all blood cells arise from

A

hematopoietic stem cells (HSCs) found in the bone marrow

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3
Q

What is multipotent

A

HSC

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4
Q

Totipotent

A

Can differentiate into all cell types, including placental cells

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5
Q

Pluripotent

A

Can become any cell type in the body.

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6
Q

Multipotent

A

can give rise to multiple, but limited, cell lineages.

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7
Q

Unipotent

A

Can only become one cell type

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8
Q

Committed

A

Have taken the first step to differentiate and cannot revert back.

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9
Q

Mature

A

Fully differentiated and perform specific functions in the body

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10
Q

What are the key characteristics of HSCs?

A

self-renewal to maintain the stem cell pool and differentiation to produce all blood cell types.

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11
Q

Long-term HSCs (LT-HSC) markers

A

CD34- CD38-

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12
Q

HSCs (LT-HSCs)

A

extensive self-renewal capabilities and can sustain hematopoiesis over a lifetime

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13
Q

short-term HSCs (ST-HSCs)

A

limited self-renewal capacity and contribute to hematopoiesis over a shorter term.

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14
Q

Short Term-HSC (ST-HSC) markers

A

CD34+ CD38+

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15
Q

Why is blood cell regeneration important?

A

Blood regeneration is vital for replenishing dead and dying cells and responding to the body’s fluctuating demands

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16
Q

Which blood cell is mostly replenished

A

RBC

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17
Q

How do HSCs relate to oncogenesis, aging, and disease?

A

abnormalities in their function can lead to cancer (oncogenesis)

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18
Q

What is the significance of HSC manipulation

A

Purified HSCs can be induced to proliferate and differentiate in vitro, offering therapeutic potential for blood diseases.

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19
Q

What is the first site of hematopoiesis in the mouse embryo?

A

The yolk sac blood islands are the first site of hematopoiesis (day 7.5) of mouse embryonic development.

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20
Q

Which embryonic structure contributes to hematopoiesis following the yolk sac?

A

The aorta-gonad-mesonephros (AGM) region becomes active around day 10.5 and is critical for generating hematopoietic stem cells (HSCs).

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21
Q

When does the fetal liver take over hematopoiesis in the mouse?

A

day 13.5, the fetal liver becomes the primary hematopoietic organ, where HSCs proliferate and differentiate extensively

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22
Q

What is the precursor to both HSCs and endothelial cells (ECs) in the yolk sac?

A

The hemangioblast is the common precursor to HSCs and ECs in early embryonic development.

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23
Q

When does hematopoiesis shift to the bone marrow?

A

After birth, the bone marrow becomes the main hematopoietic organ, housing long-term self-renewing HSCs (LT-HSCs) and short-term HSCs (ST-HSCs)

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24
Q

What role do hemogenic endothelial cells play in hematopoiesis

A

Hemogenic ECs are specialized cells within embryonic blood vessels that give rise to HSCs

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25
Q

Into what cells do HSCs differentiate during development?

A

HSCs can differentiate into various blood cell lineages, including red blood cells (RBCs), granulocytes, and lymphocytes, adjusting to the body’s changing needs

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26
Q

Where does the first wave of hematopoiesis occur?

A

In the yolk sac during the “primitive” phase.

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27
Q

Which sites are involved in subsequent waves of definitive hematopoiesis?

A

The aorta-gonad-mesonephros (AGM) region, placenta, and fetal liver

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28
Q

When do blood cells start to develop in the embryo?

A

On day 7, as embryos can no longer get oxygen from the mother.

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29
Q

Where is red bone marrow found in adults?

A

In the tibia, femur, ribs, sternum, and vertebra.

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30
Q

What are the two main niches for HSCs in bone marrow

A

The osteoblast niche and the vascular niche

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31
Q

How can HSCs be induced to leave the bone marrow?

A

Using growth factors like G-CSF.

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32
Q

What do HSCs give rise to?

A

All blood cells, including erythrocytes and megakaryocytes

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33
Q

What is the role of erythropoietin?

A

It regulates red blood cell formation.

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34
Q

What does IL-7 regulate?

A

Lymphocyte formation.

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35
Q

What cell types does GM-CSF promote the formation of?

A

Monocytes and granulocytes.

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36
Q

What constitutes primary lymphoid tissue?

A

The bone marrow and thymus.

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37
Q

What are examples of secondary lymphoid tissue?

A

The spleen and mucosa-associated lymphoid tissue (MALT), including Peyer’s patches.

38
Q

What happens if a T cell finds an antigen?

A

It becomes activated and recruits more T cells, then returns to the lymph node if it cannot find an antigen.

39
Q

What is the function of the stromal niches for HSCs?

A

Stromal cells in the bone marrow provide essential growth factors

40
Q

What is the function of the osteoblast niches for HSCs?

A

osteoblast niche influences HSC maintenance through bone morphogenic proteins.

41
Q

How can HSCs be induced to leave the bone marrow?

A

HSCs can be stimulated to exit the bone marrow using growth factors like Granulocyte Colony-Stimulating Factor (G-CSF), which is often used for stem cell harvesting.

42
Q

G-CSF

A

Granulocyte Colony-Stimulating Factor

43
Q

megakaryocytes

A

platelets for clotting

44
Q

What types of cells do HSCs give rise to?

A

HSCs differentiate into all blood cells, including erythrocytes (RBCs) without nuclei for oxygen transport, megakaryocytes that form platelets for clotting, and various cells for inflammation and immunity like monocytes, macrophages, and lymphocytes.

45
Q

Which cytokines regulate HSC self-renewal and blood cell formation?

A

Stem Cell Factor (SCF) , Erythropoietin (EPO), IL-7, and GM-CSF.

46
Q

Stem Cell Factor (SCF)

A

promotes HSC self-renewal

47
Q

Erythropoietin (EPO)

A

regulates red blood cell formation

48
Q

GM-CSF

A

boosts monocyte and granulocyte production.

49
Q

IL-7

A

oversees lymphocyte formation

50
Q

What is the difference between primary and secondary lymphoid tissues?

A

Primary lymphoid tissues like bone marrow and thymus are where lymphocytes originate and mature. Secondary lymphoid tissues like spleen and lymph nodes are where immune responses are coordinated.

51
Q

Primary lymphoid tissues

A

bone marrow and thymus are where lymphocytes originate and mature

52
Q

secondary lymphoid

A

tissues like spleen and lymph nodes are where immune responses are coordinated.

53
Q

Lymphogenesis

A

creation of lymph nodes, essential structures in the immune system where lymphocytes encounter antigens and initiate immune responses.

54
Q

What are NALT, BALT?

A

bronchial and nasopharyngeal areas respectively

55
Q

What are GALT?

A

includes Peyer’s patches, Isolated lymphoid folicles.

56
Q

What are MALT?

A

Mucosa-associated lymphoid tissue

57
Q

Why is HSC differentiation described as a complex and integrated network?

A

array of intermediate cell stages, have their own regulatory mechanisms

58
Q

What are the key components of the osteoblast niche in bone marrow?

A

osteoblasts and fibroblasts, which support hematopoietic stem cells (HSCs) through the secretion of bone morphogenic protein (BMP), and other regulatory molecules like Notch, Wnt, and PGE-2.

59
Q

How do HSCs interact with the osteoblast niche?

A

c-Kit/Kit ligand receptor-ligand pairing and are regulated by cytokines and growth factors released by stromal cells in the niche.

60
Q

What signalling molecule is prominent in the vascular niche of bone marrow?

A

CXCL12, role in the maintenance and localization of HSCs within the bone marrow environment.

61
Q

What occurs when T cells encounter antigens?

A

T cells activate, multiply, and either engage in immune response or return to lymph nodes if no antigen is present.

62
Q

What initiates lymphoid organ development?

A

LTIC cells, with specific genes activated, direct the development of lymph nodes and Peyer’s patches.

63
Q

LTIC

A

Lymphoid tissue inducer cell

64
Q

Transcriptional factors required for lymphogenesis

A

Id2, Ror-g, Ikaros

65
Q

Id2, Ror-g, Ikaros

A

Transcriptional factors required for lymphogenesis

66
Q

-/- of Id2, Ror-g, Ikaros mice outcome

A

lack pp and lymph nodes

67
Q

What role do inducer cells play in the immune system?

A

They carry signals and bind to sites to initiate the formation of lymphoid organs.

68
Q

How are organiser cells identified?

A

Through VCAM-1 or ICAM-1 antibodies, showing their clustering and binding to blood vessels for lymph node development.

69
Q

chemokines that guide LTIC

A

CCL19/21 & CXCL13 guide Inducers for lymphoid formation

70
Q

CCL19/21 (organizer chemokine) receptor?

A

CCR7

71
Q

CXCL13 (organizer chemokine) receptor?

A

CXCR5

72
Q

Where Do Lymphoid Organs Form?

A

Fetal liver and future SLT sites.

73
Q

What is an Inducer Cell?

A

A cell that expresses homing receptors and lymphotoxin, key for lymph node development.

74
Q

Role of Lymphotoxin on Inducer Cell?

A

Binds to LTβR on stromal cells, crucial for organiser cell signaling.

75
Q

Integrin Receptors on Inducer Cell and Their Ligands?

A

α4β1 integrin (binds VCAM-1), α4β7 integrin (binds MAdCAM-1).

76
Q

α4β1 integrin

A

binds VCAM-1

77
Q

α4β7

A

MAdCAM-1

78
Q

LTi lymphoid origin markers

A

CD3-CD4+CD45+ (CD- = distinct from B and T cells)

79
Q

Lymphotoxins crucial for development of LNs and PP

A

LTα and LTβ

80
Q

What receptor is essential for lymph node and Peyer’s patches development?

A

LTβR.

81
Q

What cytokine and receptor are critical for Peyer’s Patches?

A

IL-7 and IL-7R

82
Q

Which cytokine keeps inducer cells alive for lymph node development?

A

RANKL

83
Q

What cytokine and receptor are critical for Lymph nodes?

A

RANK and RANKL (TNF- related)

84
Q

What does the lymphotoxin β receptor signal into organizer cells induce?

A

Production of chemokines and VCAM.

85
Q

What do inducer cells communicate to organizer cells?

A

The need for more cells - positive feedback loop

86
Q

Which signal transduction molecules are involved in lymphoid organogenesis?

A

Jak3, NIK, IKKα, Rel-A, Rel-B, TRAF6, and NFKB2

87
Q

What’s needed to regulate the process of lymphorganogenesis?

A

A negative feedback loop.

88
Q

What do chemokines CCL19/21 and CXCL13 do in lymphorganogenesis?

A

Guide inducer cells to lymph node development sites.

89
Q

Negative Feedback in Lymphogenesis

A

IL-10 and TGF-β suppress the activity of LTi cells expression of adhesion molecules and chemokines by stromal cells, slowing down the recruitment of new cells.

90
Q

Signal saturation

A

stromal cells stop responding to lymphotoxins due to signaling saturation or active inhibition

91
Q

Positive Feedback in Lymphogenesis

A

Initial Signals: Early in lymphogenesis, lymphotoxins such as LTα1β2, produced by lymphoid tissue inducer (LTi) cells, bind to the lymphotoxin β receptor (LTβR) on stromal organizer cells in the developing lymph node.
Stromal Activation: This interaction activates the stromal cells to express adhesion molecules like VCAM-1 and ICAM-1, and to produce chemokines such as CCL19, CCL21, and CXCL13.

Innate Immunity (9 decks)

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