IMM Lec 01

Blood and Immune System - Intro and Red Blood Cells

• Blood Functions: Transports gases, nutrients, hormones, and metabolic wastes. Regulates interstitial fluid composition (pH, ions, water). Restricts fluid loss at injury sites (blood clotting). Defends against toxins and pathogens. Regulates body temperature.
• Blood Volume: 5 Liters in a 70 kg male, 4 liters in a 58 kg female.
• Blood Constituents: Plasma (46-63%) and formed elements (37-54%).
• Hematocrit: Percentage of total blood volume occupied by packed, centrifuged red blood cells. Normal values: 40-54% for males, 37-47% for females.
• Plasma Composition: Primarily water (92%). Contains amino acids, proteins (albumins, globulins, fibrinogen, transferrin), glucose, lipids, trace elements/vitamins, and gases (O2, CO2), and nitrogenous wastes. Most plasma proteins are produced by the liver.

Plasma Protein Functions

• General: Generate colloid osmotic pressure; buffer pH.
• Specific:
  • Albumins: Maintain colloid osmotic pressure; carriers.
  • Globulins (α and β): Clotting factors, enzymes, carriers. Globulins (γ): Antibodies
  • Fibrinogen: Cleaved to form fibrin during blood clotting.
  • Transferrin: Iron transport.

Formed Elements

• Erythrocytes (Red Blood Cells): 99.9% of cellular elements. Biconcave disk shape. Essentially bags filled with hemoglobin and enzymes for oxygen and carbon dioxide transport. ~5 million RBCs per microliter of blood.
• Leukocytes (White Blood Cells): 0.1% of cellular elements. Include lymphocytes, monocytes, neutrophils, eosinophils and basophils.
• Platelets: Fragments of cells involved in blood clotting.
• Differentiation count: Lymphocytes (20-40%), phagocytes (2-8%), granulocytes (50-70%).

Hematopoiesis

• Origin: In embryos, blood cells form in the yolk sac, liver, spleen and bone marrow. After birth, blood cell formation occurs in bone marrow.
• Location (adults): Bone marrow of pelvis, spine, ribs, cranium, and proximal ends of long bones.
• Process: Pluripotent hematopoietic stem cells differentiate into various progenitor cells, leading to the maturation of erythrocytes, leukocytes, and thrombocytes.
• Bone marrow composition: 25% erythrocytes, 75% leukocytes developing.
• Cytokine Regulation: Cytokines (e.g., erythropoietin, thrombopoietin, colony-stimulating factors) regulate hematopoiesis.

Red Blood Cell Structure and Function

• Structure: Biconcave discs, filled with hemoglobin and enzymes.
• Function: Transport oxygen and carbon dioxide.
• Hemoglobin: Contains iron, composed of globin (alpha and beta chains) and heme; contains oxygen molecules for transport to other body tissues. ~270 million molecules/ RBC.

Red Blood Cell Production

• Erythropoiesis: Erythropoietin (EPO) stimulates erythrocyte production in response to low oxygen levels.
• Requirements: Iron, vitamin B12 and folate are essential for this process.

Red Blood Cell Removal

• Life span: ~120 days.
• Mechanism: Old or damaged red blood cells are removed by macrophages in the spleen, liver, and bone marrow.
• Breakdown products: Hemoglobin is broken down, iron is conserved, heme is converted to bilirubin, and eliminated in bile (feces) and urine.

Anemia

• Definition: Reduced ability of blood to carry oxygen due to low red blood cell count/low hemoglobin.
• Symptoms: Tiredness, weakness, pale skin, headaches, dizziness.
• Causes:
  • Low Production: Stem cell damage (aplastic), insufficient nutrients (iron, folate, B12), low erythropoietin.
  • High Removal: Genetic defects in RBC proteins, parasitic infections, drug-induced, autoimmune reactions, and chronic bleeding (hemolytic or hemorrhagic).

Polycythemia

• Definition: Hematocrit is too high (typically >~54%).
• Symptoms: Increased blood viscosity, which can lead to reduced oxygen delivery to tissues.
• Causes: Abnormal erythrocyte precursors, low oxygen levels.