Lect 24 Leukocytes and Platelets

White blood cells larger than erythrocytes $(\approx 12-17 \mu m)$ , with prominent nuclei and a lifespan ranging from a few hours to several years depending on the type and function.
Function outside the blood, using it for transport to areas of infection, inflammation, or tissue damage.
Capable of diapedesis (migration through blood vessel walls) and positive chemotaxis (attraction to chemical signals).
Classified as granulocytes or agranulocytes based on the presence or absence of specific staining cytoplasmic granules.

Characterized by conspicuous cytoplasmic granules and lysosomes, which contain enzymes and mediators for immune responses.
Have unusually shaped nuclei with multiple lobes connected by thin strands of chromatin; the number of lobes varies among subtypes.
All are phagocytic to some extent, capable of engulfing and digesting pathogens and cellular debris.
Include neutrophils, eosinophils, and basophils.
- Neutrophils:
  - Most abundant leukocytes, making up 60-70% of the total leukocyte count.
  - Nucleus typically has 3-5 lobes when mature (polymorphonuclear leukocytes or PMNs).
  - Highly mobile phagocytes that kill bacterial cells, fungi, and some viruses; also enhance inflammation by releasing cytokines.
  - Granules contain defensins and lysozymes to destroy pathogens.
- Eosinophils:
  - Represent about 4% of leukocytes.
  - Possess a bilobed nucleus.
  - Phagocytes that primarily respond to parasitic worms by releasing cytotoxic enzymes that damage or kill the parasites.
  - Also involved in modulating allergic reactions by releasing enzymes that degrade histamine and other inflammatory mediators.
- Basophils:
  - Least abundant leukocytes, constituting less than 1% of all leukocytes.
  - Have a characteristic S-shaped (or irregularly lobed) nucleus, often obscured by large, dark-staining granules.
  - Not actively phagocytic; instead, they release chemicals like histamine and heparin from their granules to promote inflammation and prevent blood clotting, respectively.

Distinguished by the lack of prominent, visible cytoplasmic granules, though they still contain lysosomes.
The nucleus is typically spherical or kidney-shaped.
Include lymphocytes and monocytes.
- Lymphocytes:
  - Account for 20-25% of leukocytes.
  - Have large, spherical nuclei that stain intensely.
  - Crucial for adaptive immunity, with two main types:
    - B lymphocytes (B cells): produce antibodies, which are specific proteins that recognize and bind to foreign antigens, marking them for destruction.
    - T lymphocytes (T cells): do not produce antibodies; instead, they directly attack infected or cancerous cells, or regulate the immune response. Subtypes include cytotoxic T cells (killer T cells), helper T cells, and regulatory T cells.
- Monocytes:
  - Comprise 3-8% of leukocytes.
  - Characterized by a large U-shaped or kidney-shaped nucleus.
  - Migrate from the bloodstream into tissues, where they mature into macrophages.
  - Macrophages are highly efficient phagocytes that ingest dead cells, bacteria, cellular debris, and antigens.
  - Also function as antigen-presenting cells (APCs), activating T lymphocytes to initiate an immune response.

Leukocyte formation occurs in the bone marrow from hematopoietic stem cells (HSCs).
Regulated by cytokines and growth factors, such as colony-stimulating factors (CSFs) and interleukins.
HSCs divide and differentiate into myeloid and lymphoid cell lines.
- Myeloid cell line: gives rise to monocytes, granulocytes (neutrophils, eosinophils, basophils), and platelets.
- Lymphoid cell line: gives rise to B and T lymphocytes.

Smallest formed elements involved in hemostasis/blood clotting; also known as thrombocytes.
Cell fragments lacking nuclei but containing granules filled with clotting factors and enzymes, such as ADP, thromboxane A2, and serotonin, which promote platelet aggregation and vasoconstriction.
Normal platelet count ranges from $150,000$ to $400,000$ platelets per microliter of blood.
Essential for initiating and controlling the blood clotting process to prevent excessive bleeding.

Originate from hematopoietic stem cells (HSCs) in the bone marrow.
Under the influence of thrombopoietin (TPO), the myeloid cell line develops into megakaryoblasts.
Megakaryoblasts undergo repeated mitosis without cytokinesis, forming large cells called megakaryocytes.
Megakaryocytes extend long, branching arms (proplatelets) into bone marrow sinusoids (blood capillaries).
Blood flow shears off these proplatelets, fragmenting them into platelets.
Platelet production is primarily regulated by hormones like thrombopoietin, which is produced by the liver and kidneys.
Platelets have a limited lifespan of 7-10 days in the circulation before being removed by macrophages in the spleen and liver.