SCIE1440: Intro to Immunology & Hematology

Hematology Overview

• "Hema" refers to blood; "ology" denotes the study of.
• Hematology focuses on blood, blood-forming organs, blood cells, and coagulation factors.

Blood Volume

• Average adult blood volume: 4-6 liters.
• Males typically have 5-6 liters; females have 4-5 liters.
• Blood composition: ~55% plasma and ~45% cell components (WBCs, RBCs, PLTs).

Plasma Components

• Plasma is mostly water (90-92%).
• Proteins (~7%): includes albumin, globulin, fibrinogen.
• Organic solutes: urea, creatinine, glucose.
• Inorganic solutes: Na, K, Ca, Cl.
• Contains respiratory gases and enzymes, hormones, antibodies.

Blood Cells

• Three main types of blood cells:
  • Erythrocytes (RBCs): Transport oxygen and carbon dioxide.
  • Leukocytes (WBCs): Fight infections through various subtypes.
  • Thrombocytes (Platelets): Involved in hemostasis (blood clotting).

Functions of Blood Cells

• Granulocytes:
  • Combat infections and trigger immune responses.
  • Subtypes: Neutrophils, Eosinophils, Basophils.
• Lymphocytes: Vital for cellular and humoral immunity (antibody production).
• Monocytes: Phagocytosis and secretion of cytokines.
• Erythrocytes: Responsible for respiratory gas exchange.
• Platelets: Key in hemostatic functions.

Hematopoiesis

• Defined as the dynamic process of blood cell production and development.
• All blood cells originate from hematopoietic stem cells.
• Continuous turnover of cells is essential for maintaining healthy blood cell populations.

Hematopoietic System

• Major components: organs, pluripotent stem cells, regulatory factors (growth factors).
• Organs involved include bone marrow, liver, spleen, lymph nodes, and thymus.
• The system adapts to needs, increasing specific cell types during infection, bleeding, or hypoxia.

Sites of Hematopoiesis in Pregnancy and Infancy

• Mesoblastic Phase (3rd-12th week): Blood islands in the yolk sac produce embryonic hemoglobin.
• Hepatic Phase (Beginning fifth week): Liver is the primary site for RBC production until the sixth month.
• Myeloid Phase (Around 7th month): Bone marrow becomes the sole site for RBC production post-birth.

Bone Marrow Function and Development

• At birth, bone marrow is the primary site for blood cell development.
• By 18-20 years, active hematopoietic marrow is found predominantly in the sternum, ribs, pelvis, and skull.
• Adulthood: Marrow composition shifts to ~50% fat and ~50% cells, with decreased active marrow as fat infiltration occurs.

Key Objectives for Study

• Understand definitions and phases of hematopoiesis.

• Identify organs related to hematopoiesis in the fetus.

• Recognize cell maturation sequences and the essential functions of different blood cells.

• Know common skeletal sites for hematologic studies.### Erythrocytic Development Stages

• Basophilic Normoblast (Prorubricyte) Characteristics

  • Deep blue cytoplasm with potential pale perinuclear halo.
  • Nucleus is reddish-purple, with homogeneous lacy chromatin and 1-3 possible nucleoli.
  • Size ranges from 12 to 17 µm; N:C ratio is 6:1 to 4:1.
  • Comprises 1% to 5% of normal bone marrow.
  • Accumulates more RNA and hemoglobin upon maturation.

• Polychromatophilic Normoblast (Rubricyte) Characteristics

  • Smaller than basophilic normoblasts, measuring 10 to 15 µm.
  • Cytoplasm shows a blue-pink coloration due to mixed RNA and hemoglobin.
  • Nuclear chromatin is thickened and irregularly condensed; nucleoli are not visible.
  • Maturation lasts about 30 hours, rarely seen in adult peripheral blood.

• Orthochromatic Normoblast (Metarubricyte) Characteristics

  • Recognized by a solid, pyknotic nucleus with non-linear clumped chromatin.
  • Predominantly pink cytoplasm due to hemoglobin synthesis; minimal bluish hue may persist from RNA.
  • N:C ratio is 1:1 to 1:2; genotypic size is 8 to 12 µm.
  • Maturation time is approximately 48 hours.
  • Not found in the blood of adults but may appear in newborns.

• Reticulocyte Characteristics

  • Non-nucleated cell derived from the orthochromatic normoblast.
  • Contains approximately two-thirds of total hemoglobin; bluish staining remains due to RNA presence.
  • Typically 1-2% of circulating blood; matures into a fully functional erythrocyte within 1-2 days.

• Mature Erythrocyte (Red Blood Cell) Characteristics

  • Lacks nucleus, mitochondria, or ribosomes, limiting hemoglobin synthesis.
  • Specialized structure facilitates oxygen transport through microvasculature.
  • Average lifespan is approximately 120 days.

Hematopoiesis Overview

• Hematopoiesis is the production and development of blood cells.
• Initiates in the yolk sac, transitions to the liver and spleen, and settles in the bone marrow by the seventh month.
• Erythropoiesis involves development from pronormoblast to mature erythrocyte, requires specific nutrients:
  • Protein, iron, Vitamin B12, folic acid, B6, and trace metals.

Key Structural Changes During Cell Maturation

• Overall cell size decreases as cellular maturity increases; exceptions include megakaryocytes.
• Nuclear-to-cytoplasmic (N:C) ratio diminishes as the nucleus shrinks and cytoplasm expands.
• Chromatin transitions from a loose arrangement to a more clumped, condensed appearance.
• Nucleoli are present in immature cells but disappear in mature forms.

Factors Influencing Erythropoiesis

• Erythropoietin (EPO) is a key growth factor produced primarily by the kidneys, crucial for red blood cell development.
• Colony Stimulating Factors (CSFs) and Interleukins (ILs) assist in the regulation of blood cell proliferation and differentiation.
• Testing EPO levels can indicate conditions such as anemia or kidney dysfunction.

Blood Composition

• Blood consists of approximately 55% plasma and 45% formed elements (RBCs, WBCs, platelets).
• Normal adult blood volume ranges from 4 to 6 liters.
• Plasma comprises mainly water (91.5%), proteins (7%), and other solutes (1.5%).

White Blood Cells Overview

• Composition includes segmented neutrophils (50% to 70% of leukocytes), band neutrophils (2% to 6%), eosinophils (0% to 4%), basophils (0% to 2%), lymphocytes (20% to 44%), and monocytes (2% to 9%).
• Each cell type has distinct roles in immune response and defense mechanisms.

Myeloid Development and Bone Marrow Function

• By three weeks of gestation, the bone marrow becomes the sole site of red blood cell (RBC) production.
• In children, all bone marrow is active; in adults, active hematopoietic sites include the pelvis, vertebrae, ribs, sternum, skull, and proximal ends of long bones.
• Fatty marrow, which develops as a result of aging, can be reactivated to aid in compensating for anemia.

Hematopoiesis Overview

• Hematopoiesis occurs primarily in bone marrow at birth, indicating a critical role in blood cell development.
• Active marrow growth shifts from all bones at birth to specific sites, such as sternum, ribs, pelvis, vertebra, and skull, by 18-20 years of age.
• By the age of four, fat cells appear in long bones, with adult bone marrow consisting of about 50% fat.

Blood Cell Lineage

• Hematopoiesis involves the production of stem cells, progenitor cells, and precursor cells, with committed cells developing into identifiable cell lines.
• Cells in hemopoietic cords of the bone marrow move to blood via sinusoids, exhibiting a structured internal organization.

Cellular Characteristics During Maturation

• As cells mature, the overall size of white blood cells (WBCs), RBCs, and platelets decreases, except for megakaryocytes.
• Polychromatophilic normoblasts are characterized by a low nucleus-to-cytoplasm (N:C) ratio with condensed chromatin and a blue-pink cytoplasm.

Normoblast Development

• Orthochromatic normoblasts exhibit a pyknotic nucleus unable to divide, characterized by a predominately pink cytoplasm due to hemoglobin synthesis.
• Maturation of orthochromatic normoblasts lasts approximately 48 hours, with their presence in normal bone marrow between 5% and 10%.

Reticulocyte Features

• A reticulocyte is formed after the nucleus is extruded from an orthochromatic normoblast, retaining some RNA, giving it a bluish tint.
• Normally, reticulocytes constitute 1-2% of circulating blood and mature into RBCs within about one day.

Erythrocyte Functionality

• Mature erythrocytes lack a nucleus, mitochondria, or ribosomes and cannot synthesize hemoglobin but maintain limited metabolism for survival in circulation.
• Erythrocytes are crucial for transporting oxygen from the lungs to body tissues and can deform to navigate microcirculatory pathways.

This quiz covers the fundamentals of immunology and hematology, focusing on the study of blood and its components. Key topics include blood volume, blood cells, and coagulation factors. Ideal for students in the SCIE1440 course seeking to reinforce their understanding of these essential biological systems.