Blood and Immune Cell Development

Blood and Immune Cell Development

Features of Blood

• Blood is classified as a liquid tissue.

• It consists of two main components:

  • Cellular components:

    • Red blood cells (erythrocytes).

    • Platelets (thrombocytes).

    • Different kinds of white blood cells (leucocytes).

  • Plasma: The liquid in which these cellular components are suspended.

Functions of Blood

Blood performs three critical functions:

Transport

Blood transports various substances throughout the body, including:

• Gases, specifically oxygen (O{2}) and carbon dioxide (CO{2}).

• Food molecules (e.g., glucose, lipids, amino acids).

• Ions (e.g., Na^{+}, Ca^{2+}, HCO_{3}^{-}).

• Waste products (e.g., urea).

• Hormones.

• Heat, helping to regulate body temperature.

• Cells and other components of the immune system.

Defence

Blood plays a crucial role in defending the body against:

• Infections from pathogens.

• Injury.

• Cancer cells.

Repair

Blood is essential for the repair processes of the body following an insult or injury, such as initiating clotting to prevent blood loss.

How Factors are Transported Around the Body

Transport is facilitated by the cardiovascular system, which comprises two interconnected systems:

Circulatory System

• The heart actively pumps blood through two separate circuits:

  • Systemic circuit: Transports blood to the body.

  • Pulmonary circuit: Transports blood to the lungs.

• Each circuit consists of arteries, capillaries, and veins.

Lymphatic System

• This system comprises a series of canals filled with lymph fluid, which is derived from the interstitial space.

• Fluid moves passively through the contractions of skeletal muscle and other body movements.

• All lymphatic fluid filters through at least one lymph node before re-entering the general circulation.

Blood Components in Detail

When blood is centrifuged, it separates into three distinct layers:

Plasma

• The top, yellowish liquid layer, constituting approximately 55-60% of blood volume.

• Composition:

  • Mainly water.

  • Ions (e.g., Na^{+}, Ca^{2+}, HCO_{3}^{-}).

  • Organic molecules (e.g., food like glucose, lipids, amino acids; wastes like urea).

  • Proteins.

  • Trace elements and vitamins.

  • Gases (e.g., dissolved oxygen and carbon dioxide).

• Plasma Proteins:

  • Albumin:

    • Constitutes about ~54% of plasma protein.

    • Functions as a carrier for various substances such as steroids and fatty acids.

    • Significantly contributes to plasma osmotic pressure, which is vital for maintaining blood volume, especially in trauma.

  • Globulins:

    • Make up about ~38% of plasma protein.

    • Alpha globulins: Transport bilirubin and certain steroids.

    • Beta globulins: Transport iron and copper.

    • Gamma globulins: Are antibodies, crucial components of the immune system.

  • Fibrinogen:

    • Comprises approximately ~7% of the plasma proteins.

    • It is a key part of the clotting process, being converted to fibrin to form blood clots.

  • Other proteins: Include hormones (e.g., insulin) and cell signalling molecules (e.g., cytokines, chemokines).

Buffy Coat

• A thin, whitish layer located between the plasma and red blood cells after centrifugation.

• Consists of white blood cells (leukocytes) and platelets.

Erythrocytes (Red Blood Cells - RBCs)

• The bottom, deepest red layer, constituting approximately 40-45% of blood volume.

• Abundance: Most numerous cell type in the blood, around ~5\cdot10^6/\mu L .

• Structure: Lack nuclei, but are densely packed with iron-containing hemoglobin.

• Function: Major role in the transport of gases (oxygen and carbon dioxide) between the lungs and tissues.

• Life Cycle: RBCs are terminally differentiated, meaning they cannot divide.

  • They have a relatively short lifespan of 120 days.

  • Old or damaged RBCs are ingested by leucocytes primarily in the liver and spleen at a rate of approximately 3 million per second.

Platelets (Thrombocytes)

• Origin: Cell fragments produced from large bone marrow cells called megakaryocytes.

• Count: Blood normally contains about ~1.5-4.5\cdot10^5/\mu L .

• Function: Their primary role is in blood clotting (coagulation).

  • When blood vessels are cut or damaged, they initiate a process to prevent blood loss.

  • A blood clot consists of a plug of platelets enmeshed in a network of insoluble fibrin molecules.

White Blood Cells (Leucocytes)

• Count: Under normal conditions, blood contains approximately ~5\cdot10^3/\mu L WBCs.

• Structure: These cells possess nuclei, but their morphology (shape) varies significantly depending on the type.

• Function: Their key role is in defending the body from 'insults' such as injury, infection, and cancer, as well as contributing to repair processes.

• Major Types: Leucocytes are broadly divided into two major categories:

  • Granulocytes: Characterized by the presence of granules in their cytoplasm.

    • Neutrophils:

      • The most abundant WBC, making up about 50-70\% .

      • Their key role is the destruction of microbes, particularly bacteria.

      • Their numbers significantly increase in response to bacterial infections.

      • Possess neutral-staining granules containing a range of antimicrobial enzymes.

      • Have a short lifespan in the blood, typically around ~6-10 hours.

    • Eosinophils:

      • Normally present at low levels in the blood, comprising 1-4\% of WBCs.

      • Their numbers sharply increase in certain diseases, especially infections caused by parasitic worms.

      • Are cytotoxic cells, releasing the contents of their eosinophilic granules to kill invading organisms.

    • Basophils:

      • The rarest WBC, typically less than 1\% .

      • Their numbers increase during infection and inflammation.

      • They leave the bloodstream and accumulate at sites of infection or inflammation.

      • Discharge the contents of their basophilic granules, which contain mediators like histamine.

  • Agranulocytes: Lack visible granules in their cytoplasm.

    • Monocytes:

      • Comprise approximately 2-8\% of WBCs.

      • Monocytes circulate in the blood briefly before leaving the bloodstream and developing into specialized cells, primarily macrophages.

      • Macrophages: Large, highly phagocytic cells that engulf foreign material, dead cells, and dying cells.

    • Lymphocytes:

      • The second most common WBC, accounting for 20-40\% of the total.

      • There are several kinds of lymphocytes, each with distinct functions in the immune system.

      • B lymphocytes (B cells): These are the most common type and are responsible for producing antibodies.

      • T lymphocyte (T cell) subsets:

        • Helper T cells (T_{h}): Enhance the production of antibodies by B cells and recruit other immune cells, such as macrophages and neutrophils, to sites of infection.

        • Cytotoxic T cells (T_{c}): Directly kill virus-infected cells and tumor cells.

        • Regulatory T cells (T_{reg}): Play a crucial role in controlling and suppressing excessive immune responses, helping to maintain immune tolerance.

      • Natural killer lymphocytes (NK cells): Are part of the innate immune system and can kill virus-infected cells and tumor cells without prior activation.

Blood Cell Development – Haematopoiesis

• Definition: Haematopoiesis is the ongoing process of blood cell development that occurs throughout an individual's life.

• Rate of Production: The body contains an enormous number of blood cells, and most are short-lived once released into the bloodstream (e.g., neutrophils have a half-life of hours, erythrocytes a half-life of months).

• Therefore, they must be constantly replaced, with approximately ~10^{11} new blood cells produced every day.

Haematopoiesis – Early Development

• Yolk sac 'blood islands': The first primitive erythrocytes develop here.

• AGM (Aorta-Gonad-Mesonephros) region: The first blood and immune precursors originate in this embryonic region.

• Foetal liver: These precursors then populate the foetal liver (and later the thymus) to generate the first mature blood cells.

Haematopoiesis – Adult Bone Marrow

• Primary Site: The bone marrow is the major source of blood cells in adults, weighing approximately ~3 kg in an adult male.

• Anatomy: It is composed of a network of epithelial cell-lined sinusoids interspersed with islands of haematopoietic cells.

• Supportive Stroma: The haematopoietic cells are supported by connective tissue elements that form the bone marrow stroma, including fibroblasts, adipose tissue, and endothelial cells.

• Location: Found principally in the pelvis, ribs, and long bones.

• Types of Marrow:

  • Blood cell development occurs in the active red marrow.

  • At birth, bone marrow is 100\% red marrow, but over time, it is gradually replaced by inactive yellow marrow (up to 50\% ), which is mainly composed of adipose tissue.

Key Organs/Tissues of the Blood and Immune System

Bone Marrow

• As detailed above, it is the primary site for adult haematopoiesis, producing all blood cells.

Spleen

• The spleen has diverse vital functions:

  • Blood cell development: It is involved in embryonic blood cell development and can contribute to adult haematopoiesis in response to conditions like infection.

  • Immunity: Contains 25\% of the body's lymphoid mass, making it a critical immune organ.

  • Filtration: Responsible for the removal of old/damaged red blood cells, bacteria, and other particulate matter from the blood via resident macrophages.

Thymus

This organ is the key site for the maturation and differentiation of T cells (T{h}, T{c}, T_{reg}), which are crucial for adaptive immunity.

Lymph Nodes

• Structure: Encapsulated, kidney-shaped organs.

• Distribution: Distributed along lymphatic vessels, often found in clusters.

• Contents: They contain a high concentration of lymphocytes and other immune cells, acting as filtration centers for lymph fluid and sites for immune responses.