Hematopoietic Chapter 4 Quiz

Ontogeny of Hematopoiesis

• Hematopoiesis initiates around the eighteenth day after fertilization in the yolk sac of the human embryo.
• Erythrocytes are generated for oxygen transport to developing tissues.
• Intraembryonic hematopoiesis starts in the aorta-gonads-mesonephros (AGM) region along the developing aorta.
• The liver becomes the main site for blood cell production by the third month of fetal development, overtaking the yolk sac and AGM.
• As development advances, hematopoiesis shifts to organs like the spleen, kidney, thymus, and lymph nodes, before primarily settling in bone marrow by six months gestation.

Hematopoietic Organs and Tissues

• Adult hematopoietic system consists of bone marrow, thymus, spleen, and lymph nodes.
• Bone marrow and thymus are primary lymphoid tissues where T and B cells develop.
• Secondary lymphoid tissues include spleen and lymph nodes, involved in the response to antigens.

Bone Marrow Structure

• Bone marrow is a blood-forming tissue found within spongy bone and consists of vascular and hematopoietic compartments.
• Vascular compartment includes nutrient arteries, periosteal arteries, and sinuses, supplying the marrow.
• Hematopoietic compartment is where blood cell formation occurs, supported by a stroma composed of macrophages, reticular cells, and adipocytes.

Functions of Bone Marrow Stromal Cells

• Macrophages phagocytose extruded erythrocyte nuclei and abnormal cells while secreting hematopoietic cytokines.
• Reticular cells produce fibers that support hematopoiesis and hold vascular sinuses together.
• Adipocytes affect the volume of functional bone marrow and provide steroids influencing erythropoiesis.

Hematopoiesis in Bone Marrow

• Erythroblasts make up 25-30% of marrow cells, developing in erythroblastic islands regulated by macrophages.
• Granulocytes and megakaryocytes are produced in proximity to marrow sinuses, with megakaryocytes generating platelets.
• Lymphocytes develop in lymphoid aggregates, with some maturing into T lymphocytes in the thymus and B lymphocytes remaining in the marrow.

Bone Marrow Changes

• Hyperplasia occurs with increased hematopoiesis, while hypoplasia signifies inactive hematopoietic tissue.
• Conditions causing hyperplasia include acute blood loss, chronic anemia, and leukemia.

Thymus

• The thymus is located in the upper anterior mediastinum and is crucial for T lymphocyte maturation.
• Comprised of an outer cortex with densely packed thymocytes and a central medulla with more mature cells; it is well-developed at birth and shrinks after puberty.

Spleen

• The spleen, found in the upper left abdomen, contains the largest accumulation of lymphocytes and macrophages.
• Functions include filtration of foreign substances, destruction of old RBCs, storage of platelets, and aiding immune defense.

Spleen Pathways

• Blood enters through the splenic artery, with vessels branching to white pulp, red pulp, or marginal zones, following rapid or slow transit pathways for filtration.

Functions of Lymph Nodes

• Lymph nodes filter foreign particles from lymph using dendritic cells and macrophages and initiate immune responses.
• Enlargement of lymph nodes indicates lymphadenopathy, caused by inflammation, prolonged immune responses, or malignancies.

Mucosal Associated Lymphoid Tissue (MALT)

• MALT is a collection of lymphocytes in mucosal surfaces, including Peyer’s patches, tonsils, and appendix.
• Functions to trap antigens and rapidly initiate immune responses.

Hematopoiesis Overview

• Tissue homeostasis is maintained by balanced cellular proliferation, differentiation, and apoptosis.
• Hematopoiesis involves the replacement of circulating cells, with a daily production of about 2 x 10^11 RBCs and similar quantities of WBCs and platelets.

Stem Cells

• Hematopoietic stem cells (HSCs) are undifferentiated and give rise to all marrow cells, known for high self-renewal capacity.
• HSCs reside in specific "stem cell niches" within the bone marrow, with quiescent populations maintaining lifelong stem cell levels.### Hematopoietic Stem Cells (HSC)
• HSCs are precursor cells responsible for generating hematopoietic lineage and vascular endothelium during embryonic development.
• Long-term HSCs (LT-HSCs) are more primitive than short-term HSCs (ST-HSCs) and are key to repopulating depleted hematopoietic tissue.
• HSCs can undergo three fates: self-renewal, differentiation into common lymphoid progenitors (CLPs) or common myeloid progenitors (CMPs), or apoptosis.
• Cell fate decision is regulated by specific transcription factors.

Progenitor Cells

• Progenitor cells arise from HSCs and retain differentiation potential initially but are restricted in lineage potential over time.
• Multipotential progenitor cells (MPPs) begin differentiation, eventually leading to unilineage or committed progenitor cells.
• Progenitor cell compartment contains precursor cells leading up to morphologically recognized cells.

Characteristics of Progenitor Cells

• Approximately 3% of total nucleated hematopoietic cells are progenitor cells.
• These cells do not exhibit true self-renewal and can produce colonies in vitro known as colony-forming units (CFUs).
• CFU types include CFU-GEMM for granulocytes, erythroid cells, monocytes, and megakaryocytes, as well as CFU-GM for granulocytes and monocytes.

Maturing Cells

• Over 95% of total hematopoietic precursor cells are committed unipotential cells, recognizable morphologically.
• They can be amplified through proliferation and recognized at the blast stage, the first identifiable cell in hematopoiesis.

Hematopoietic Growth Factors (Cytokines)

• Cytokines are produced by various cells including monocytes, macrophages, and T lymphocytes, and are mainly produced by bone marrow stromal cells.
• Their functions are pleiotropic and not lineage-specific, affecting multiple hematopoietic processes.
• Notably, erythropoietin is produced primarily in the kidney.

Lineage-Specific Regulation

• Erythropoiesis involves BFU-E regulated by IL-3 and GM-CSF and CFU-E driven mainly by erythropoietin.
• Granulocyte and monocyte lineages derive from CFU-GM and are regulated by GM-CSF, IL-3, M-CSF, and G-CSF.
• Megakaryocytes derive from CFU-Mk, influenced by IL-11 and thrombopoietin (TPO).

Negative Regulators of Hematopoiesis

• Negative regulators limit hematopoietic precursor cell production and may inhibit hematopoiesis by reducing stimulating factors or increasing inhibitory factors.

Cytokine Signaling Pathways

• Cytokines exert effects by binding to membrane receptors, triggering intracellular signaling pathways that recruit transcription factors affecting gene expression.
• Specific examples include the role of JAK-STAT signaling in cytokine receptor activation, leading to gene transcription modulations.

Clinical Use of Hematopoietic Growth Factors

• Advances in cloning allow the large-scale production of cytokines for therapeutic applications in hematopoietic disorders.
• Hematopoietic growth factors are utilized in clinical settings to support recovery from hematopoietic dysfunctions.

This quiz covers Chapter 4 of Hematopoietic Organs, focusing on the ontogeny of hematopoiesis. Learn about the early development stages, including the role of the yolk sac and the aorta-gonads-mesonephros region in blood cell production. Test your knowledge on key concepts related to the formation of erythrocytes and macrophages during embryonic development.