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GRANULOCYTE DEVELOPMENT/MORPHOLOGY/FUNCTIONS


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INTRODUCTION

  • White blood cells, also called leukocytes or leucocytes are the cells of the immune system that are involved in protecting the body against both infectious diseases and foreign invaders
  • They make up approximately 1% of the total blood volume in a healthy adult, making them substantially less numerous than the red blood cells

Location

  • Leukocytes are found throughout the body, including;
    • The blood; and
    • Lymphatic system Production
  • All white blood cells are produced and derived from multipotent cells in the bone marrow known as haematopoietic stem cells
  • Their development along different lineages is governed by external stimuli including cytokines, matrix proteins and other cellular products within the marrow environment
  • The combination of specific cytokines and growth factors influence the maturation of WBC progeny along specific lineage Functions
  • They have fundamental roles in defense against invading microorganisms and the recognition and destruction of neoplastic cells
  • As well as critical roles in the acute inflammation
  • Through their phagocytic functions, especially Neutrophils and monocytes, they are important in clearing senescent and apoptotic cells
  • Hence, allowing tissue repair and remodeling

 

Blood Cells

CLASSIFICATION

  • The leukocytes are basically divided into 2 broad groups
    • Phagocytes
    • Immunocytes

Phagocytes

  • The phagocytes comprise the cells of the innate immune system which can act very quickly after an infection
  • The phagocytes are further classified as;
    • Polymorphonuclear phagocytes – characterized by multilobed nucleus

 Neutrophils

 Eosinophils

 Basophils

  • Mononuclear phagocytes Monocytes

 Macrophages

Immunocytes

  • The immunocytes (lymphocytes) mediate the adaptive immune response which can develop immunological memory (e.g. after vaccination)
  • They are;
    • Lymphocytes T-Lymphocytes

 B-Lymphocytes

  • Plasma cells

CHARACTERISTICS OF PHAGOCYTES

Functions

  • The phagocytes specialize in the destruction of foreign matters and thus have a fundamental role in the body’s defense against invasion by micro-organisms
  • They also recognize and destroy tumor cells
  • They ingest apoptotic cells, thereby aiding organ remodeling and tissue repair
  • The phagocytic cells of all types modulate both cellular and humoral immunity through the synthesis and release of immuno-regulatory proteins and cytokines
  • They have a major role in allergy and inflammatory processes Migration
  • The phagocytes are produced in the bone marrow from a common haemopoietic stem cell
  • Following maturation and storage in the marrow they are released to the circulation
  • They exist in the blood in a relatively quiescent state and marginate to the endothelium before moving to the tissues
  • During infection, they are rapidly recruited to specific sites and are activated to ingest and kill invading pathogens

Production, Lifespan & Elimination

  • The development and activity of phagocytes are normally tightly regulated at all stages by a series of;
    • Chemostatic factors
    • Cytokines and
    • Growth factors such as IL-1, IL-3, IL-5, IL-6, IL-11, GM-CSF, G-CSF, M-CSF
  • Inappropriate stimulation and failure of regulation however, leads to destruction of host tissue during inflammatory diseases
  • At the end of their lifespan, phagocytes undergo an ageing process with surface changes resulting in recognition and removal by macrophages
  • Cytokines can prolong the life of phagocytes by blocking this process
  • The blood granulocytes and monocytes are formed in the bone marrow from common progenitor cells
  • From the progenitor cells, it moves to the next stage
    • Myeloblast, promyelocyte and myelocytes from a proliferative or mitotic pool
    • While the metamyelocytes, band and segmented granulocytes, make up the post mitotic maturation compartment

Duration

  • The development occurs over 14 days in the marrow where only the matured cells are released into the peripheral blood
  • The differentiation stage between myeloblast and the myelocyte takes 7-8 days and is accompanied by cell division
  • Thereafter, myelocyte matures to metamyelocyte, the band form and the segmented neutrophils
  • This process takes 6-7 days and occur without cell division

Lifespan

  • Large numbers of band and segmented neutrophils are held in the marrow as a ‘reserve pool’ or storage compartment
    • Lifespan in the marrow – 4-5 days
  • Following their release, they spend few hours in the circulation before moving into the tissues where they perform their phagocytic functions
    • Lifespan in the circulation – 6-10 hours Granulocyte Populations
  • 2 populations exist in circulation
    • The circulating; and
    • Marginal pools
  • They are found in the blood and tissues and constitutes about 65% of circulating leukocytes in man

NEUTROPHILS (POLYMORPHS)

  • Neutrophils are commonly referred to as polymorphonuclear (PMN) leukocytes
  • They are the most abundant white blood cells, constituting 60-70% of the circulating leukocytes
  • They include 2 functionally unequal subpopulations;
    • Neutrophil-killers and
    • Neutrophil-cagers

Morphology

  • This cell has a dense nucleus consisting of 2-5 lobes
  • And a pale cytoplasm with an irregular outline with many fine pink-blue (Azurophilic) granules
  • The granules are divided into primary and secondary;
    • Primary – appears at promyelocytic stage and contains;

 Myeloperoxidase; and

 Other acid hydrolases

  • Secondary – appears at myelocyte stage and predominantly in the mature neutrophil and contains;

 Lactoferrin

 Lysozyme; and

 Other enzymes

  • Both the granules are lysosomal in origin Lifespan
  • The lifespan of Neutrophils in the blood is only 6-10 hours

Development

  • Neutrophils precursors do not usually appear in normal peripheral blood but are present in the marrow
  • They are;
    • Myeloblast
    • Promyelocyte
    • Myelocyte
    • Metamyelocyte
    • Band form

Myeloblast

  • The earliest recognizable precursor of neutrophil. A large cell with variable sizes
  • It has a large nucleus and 2-5 pale-blue nucleoli and a fine chromatin meshwork with scanty basophilic cytoplasm
  • There are no granules at this stage
  • The bone marrow contains up to 5% of myeloblast
  • The myeloblast give rise to the next cell

Promyelocyte

  • A large cell, bigger than the myeloblast
  • With centrally located nucleolus in the nucleus
  • And reddish-purple primary cytoplasmic granules
  • It gives rise to↓

Myelocyte

  • A cell with more abundant basophilic cytoplasm
  • Nuclear chromatin is more aggregated and there are no nucleoli
  • Secondary granules start at this stage
  • It matures to the next stage

Metamyelocyte

  • Has indented or horse-shoe nucleus
  • And cytoplasm filled with primary and secondary granules

Band form

  • Stab or juvenile
  • It may occur in normal peripheral blood

Segmented

  • Contain 2-5 lobes nucleus and fine violet-pink cytoplasmic granules Granules of the Polymorphs
  • There are 5 different types of granules
    • Primary (Azurophilic) granules – contain;

 Myeloperoxidase

 Elastase

 Lysozyme

  • Specific granules – contain; Collagenase
  • Tertiary granules – contain; Gelatinase
  • Microperoxisomes – contain; Catalase
  • Organelles – contain;

 Alkaline phosphatase

Bone Marrow Nucleated Cells Composition

  • Myeloblast                                                 1-4%
  • Promyelocyte                                     5%
  • Myelocyte                                                 12%
  • Metamyelocyte                                     22%  Mature neutrophil                                            20%

Functions

  • They are usually first responders to microbial infection
  • They defend against bacterial or fungal infections due to their ability to ingest and kill microorganisms
  • These cells are not able to renew their lysosomes (used in digesting microbes) and die after having phagocytozed a few pathogens and are found in large amount in pus
  • They synthesize cytokines in response to stimulation and immunomodulation

EOSINOPHILS

  • Constitute a minor species of granulocytes, comprising 1-4% of total white cells (0.04-

0.44 × 109/L)

  • This count fluctuates throughout the day, seasonally and during menstruation  It rises in response to;
    • Allergies
    • Parasitic infections
    • Collagen diseases and
    • Disease of the spleen and central nervous system
  • They are rare in the blood, but numerous in the mucous membranes of the respiratory, digestive, lower urinary tracts and skin

Morphology

  • Mature eosinophils have 2-3 lobes, and numerous coarse brownish-red granules and slightly bigger than neutrophils

Lifespan

  • Blood transit time 3-8 hours

Development

  • This is regulated by IL-5 and follows the neutrophil pattern Granules of the Eosinophils
  • Mature eosinophils have 3 types of granules; ü Primary granules – contain;

 Eosinophil peroxidase and

 Charcot-Leyden crystal protein

  • Secondary granules – contain;

 Most basic proteins – cytotoxic to mammalian cells and parasites through membrane damage

  • Eosinophil cationic protein and eosinophil derived neurotoxin[1] Function
  • They enter inflammatory exudates and have a special role in;
    • Allergic responses
    • Defense against parasites and
    • Removal of fibrin formed during inflammation
  • Eosinophils have less phagocytic and bactericidal activity, but have an important role in mediating hypersensitivity reactions such as;
    • Bronchial asthma and
    • Skin inflammation
  • It secretes cytokines like IL-1, IL-3, IL-6, IL-8 and TNF-β
  • Proteins released from eosinophils also induce histamine release from basophils and mast cells thus, amplifying the inflammatory response
  • Eosinophil granular proteins are also toxic to bacteria and multicellular parasites
  • It has a role in wound healing and tissue remodeling by modulating the deposition of extracellular matrix proteins
  • The gelatinase secreted by eosinophil may mediate metastasis of tumors by degrading extracellular matrix proteins

BASOPHILS AND MAST CELLS

  • Basophils comprise 0.2-1% of circulating leukocytes (NR[2] – 0.01-0.1 × 10/L)
  • And about 0.3% nucleated cells in the marrow
  • Mast cells are predominantly located in the tissue
  • There are 2 types of mast cells
    • Connective tissue mast cells – found on;

 The skin

 Intestinal mucosa

  • Mucosal mast cells – residing in;

 Intestinal mucosa

 Lung alveoli

Morphology

  • Mature basophils are multilobed with dark cytoplasmic granules which overlie the nucleus and contain heparin and histamine Functions
  • Primary effector in allergic reactions - basophils are chiefly responsible for allergic and antigenic response by releasing the chemical histamine, causing the dilation of blood vessels
  • Hypersensitivity reactions
  • Chemotactic for neutrophils

MONOCYTES AND MACROPHAGES

  • About 5% of leukocytes in the circulation 0.2-0.8 × 109/L

Morphology

  • They are larger than other peripheral blood leukocytes
  • And possess a large central oval or indented nucleus with clumped chromatin  The cytoplasm is abundant and greyish-blue containing granules Lifespan
  • Half-life in circulation is 17 hours
  • Their extravascular lifespan after their transformation to macrophages may be as long as several months or even years

Development

  • The precursors are monoblasts and promonocytes
  • They migrate to the tissues at a fairly constant rate and become macrophages or dendritic cells
  • In the tissue, they self replicate without replenishment from blood
  • GM-CSF and M-CSF are involved in their production and activation
  • They are called different names in various tissues;
    • Kidney                                     Kidney intraglomerular mesangial cells
    • Brain                                     Microglia
    • Lung                                       Alveolar macrophages
    • Liver                                       Kupffer cells
    • Spleen                                                Sinus macrophages
    • Bone marrow                         Macrophages ü Lymph node                                      Macrophages

Functions

  • They have role in the control of both primary and secondary immune response
  • They;
    • Scavenge debris
    • Aid wound healing
    • Sequester and detoxify injurious materials
    • Remove senescent or dying cells
  • They are active in bone resorption and remodeling
  • They can mediate the killing of tumor cells by antibody-dependent and independent mechanisms, as well as destroy pathogens

 

 

[1] Yh! That’s the 3rd granules “in the material”. Ugh!

[2] Normal Range