Leucocytes and Granulocytes Overview

Leucocytes

Motile cells that leave the bloodstream and migrate to tissues
Play a role in body immunity
Most granulocytes undergo apoptosis in connective tissue
Number about 6,000 – 10,000/mm³ in blood
True cells with lobulated nuclei (except in lymphocytes)
Few mitochondria, Golgi, poorly developed RER and glycogen granules (anaerobic glycolysis)
Short lifespan (most last hours to days)
Leucocytosis: An increase in the total number above 11,000/mm³
Leucopenia: A decrease in the total number below 4000/mm³

Granulocytes

Neutrophils: (Polymorphs or Polymorph-nuclear leucocytes)
- Constitute 60%-70% of circulating leukocytes
- Kill and phagocytose bacteria
- 12-15 μm in diameter
- Band neutrophils (immature) are not more than 3-5% in blood film under normal condition
- Life span: 6-8 hours in blood and 1-4 days in connective tissue
- Inactive in circulating blood and become activated on connective tissue
- Nucleus has two to five lobes linked by thin chromatin strands
- Cytoplasm: contains two types of granules:
  - Neutrophilic (specific) granules: Smaller, 80% of granules, stain faintly pink
    - Contain ECM-degrading enzymes such as collagenases
    - Breakdown matrix components and participate in pus formation
    - Contain alkaline phosphatase, and lactoferrin (bacteriostatic).
  - Azurophilic granules: Larger dense lysosomes, 20% of granules
    - Involved in killing and degrading engulfed microorganisms
    - Contain hydrolytic enzymes, proteolytic and lipolytic enzymes (bacteriotoxic)
    - Release cytokines and chemokines that attract other leukocytes to the site of inflammation
- Neutrophilia: (>75%) signifies an increase in numbers during acute inflammatory conditions and pyogenic infections.
- Neutropenia: A decrease in numbers

Eosinophils

Constitute 2-4% of circulating leukocytes
Have a bilobed nucleus connected by a thin chromatin strand
Cytoplasm: contains two types of granules:
- Specific granules: Larger, stain reddish-orange with eosin, are oval shaped, and contain crystalloid structures
  - Involved in killing parasitic worms
  - Release enzymes that break down the parasite’s cuticle and help with the destruction of the parasite
  - Also, play a role in allergic reactions
- Azurophilic granules: Smaller, stain blue-purple, are lysosomes, and contain hydrolytic enzymes
Eosinophilia: An increase in numbers can occur in parasitic infections and allergic reactions.

Basophils

The least abundant granulocytes (0.2%)
Involved in allergic and inflammatory reactions
Release histamine, heparin, and leukotrienes from their granules
- Histamine causes vasodilation and increased vascular permeability
- Heparin is an anticoagulant
- Leukotrienes are chemotactic for other leukocytes and contribute to inflammation
Basophilia: An increase in numbers is associated with allergic reactions and some parasitic infections.

Agranulocytes

Lymphocytes:
- Smallest leukocytes
- Responsible for adaptive immune responses
- Small Lymphocyte: (6-8μm in diameter):
  - Has a large, round nucleus that occupies most of the cell
  - Thin rim of cytoplasm with a few small, azurophilic granules
  - Play a role in antibody production
  - Are involved in cell-mediated immunity and humoral immunity
- Medium-sized Lymphocytes: (10-12μm in diameter)
  - Larger in size and show the presence of a prominent nucleolus
  - More cytoplasm than the small lymphocytes
  - Are active in antibody production
- Large Lymphocytes: (15-20 μm in diameter):
  - Involved in cell-mediated immunity
  - Possess abundant cytoplasm that often shows an irregular shape with a large nucleus
  - May contain a nucleolus
  - Have a prominent Golgi apparatus and rough endoplasmic reticulum
Monocytes:
- Largest leukocytes
- Play a role in both innate and adaptive immune responses
- Phagocytes: engulf and destroy pathogens and cellular debris
- Antigen-presenting cells: Show antigens to lymphocytes to stimulate an immune response
- Development: differentiate into macrophages and dendritic cells
- Histologically:
  - Nucleus: Large, indented, or kidney-shaped and can have a fine chromatin pattern
  - Cytoplasm: Abundant, pale blue staining, and contains occasional azurophilic granules (lysosomes)
- Clinical Importance of Monocytes:
  - Inflammation: migrate to sites of inflammation, where they differentiate into macrophages and play a critical role in responding to inflammation.

Leukopoiesis

The process of leukocyte production
Occurs in bone marrow
Starts with pluripotent hematopoietic stem cells (HSCs)
Granulopoiesis:
- The process of granulocyte development
- Steps:
  - Myeloblast: Large cell with a large, round nucleus and fine chromatin, containing prominent nucleoli
  - Promyelocyte: Basophilic cytoplasm with prominent azurophilic granules (lysosomes)
  - Myelocyte: Smaller, with an eccentric nucleus and developing specific granules
  - Metamyelocyte: Nucleus becomes indented, and specific granules are more prominent.
  - Band neutrophil: Nucleus is elongated and horseshoe-shaped
  - Segmented neutrophil: Mature stage, nucleus has 2 or 5 lobes connected by thin strands of chromatin.
Lymphopoiesis:
- The process of lymphocyte development
- Steps:
  - Prolymphocyte: A large cell with a large, round nucleus, prominent nucleoli, and basophilic cytoplasm
  - Lymphoblast: Smaller, with a more condensed nucleus and a thin rim of cytoplasm
  - Small Lymphocyte: Mature cell with a large, round nucleus, dense chromatin, and minimal cytoplasm
Monopoiesis:
- The process of monocyte development
- Steps:
  - Monoblast: A large cell with a prominent nucleolus, fine chromatin, and basophilic cytoplasm
  - Promonocyte: Smaller, with a more condensed nucleus, azurophilic granules, and darker cytoplasm
  - Monocyte: Mature cell, a large, indented, or kidney-shaped nucleus and abundant pale blue cytoplasm.