Leukocytes

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Leukocytes (WBC)

Mobile unit of body’s defense system

• Formed partially
– In the bone marrow
• Granulocytes, monocytes, few lymphocytes
– In the lymph tissue
• Lymphocytes & plasma cells
After formation
• Transported in blood
– Different parts of the body where they are to be used

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Characteristics of Leukocytes

• Types
– Polymorpho nuclear neutrophils
– Polymorpho nuclear eosinophils
– Polymorpho nuclear basophils
– Monocytes
– Lymphocytes & plasma cells
– Platelets

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Characteristics of Leukocytes

Two main groups of mature leukocytes

• Based on appearance after staining with
polychromatic dye
– Granulocytes
– Agranulocytes

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Characteristics of Leukocytes

Granulocytes
• Have abundant membrane bound intracellular
granules
– granulocytes
• Also have multilobed nucleus
– Polymorpho nuclear

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Characteristics of Leukocytes

Granulocytes
• Eosinophils
– Take up red dye eosin
• Polymorpho nuclear eosinophils
• Basophils
– Take up blue dye “basic dye”
– Polymorpho nuclear basophils

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Characteristics of Leukocytes

Granulocytes
• Neutrophils
• Granules have little affinity for either dye
– Polymorphonuclear neutrophils

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Characteristics of Leukocytes

Agranulocytes
• Monocytes, lymphocytes & platelets
– Have no granules seen in their cytoplasm after
staining
• Monocytes, lymphocytes
– Have large spherical nucleus
– also called Mononuclear leukocytes

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Number & Distribution

• Normal adults
– Have about 4,000 – 11,000 wbc/L of blood

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Number & Distribution

• Normal % of different types

• Neutrophils 50 – 70%
• Eosinophils 1 – 4%
• Basophils 0.1 – 0.4%
• Monocytes 2 – 8%
• Lymphocytes 20 – 40%
• Total platelets
– 150,000 – 300,000/ L of blood
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Genesis of WBC

• Like the RBCs the WBC originate from the

PHSC in bone marrow
• It differentiates to form
– Myelocyte stem cell
• CFU-GM
– Granulocytes (N, E, B), Monocytes
• CFU-M (megakryocyte)
– Platelets
– Lymphoid stem cell
• T-lymphocyte, B-lymphocyte

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 Genesis of Blood Cells

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 Lymphocytes

Lymphoblast

Bursal equiv tissue Thymus

B-Lymphocyte T-Lymphocyte

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WBC lifespan

• Granulocytes once released from blood

• Have a lifespan of
– About 4 - 8 hrs and another
– 4 – 5 days in tissues
• Lifespan is greatly reduced in severe infection

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WBC Lifespan

• Monocytes
– Short transit time in blood
• About 10 – 20 hrs
– Once in tissues
• Swell to large size
– To form macrophages
• In this form they can live for several months to
yrs

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WBC Lifespan

• Lymphocytes
• Enter the circulatory system continually
– After few hrs in circulation
– They pass back in tissue
• Have a lifespan of
– Weeks, months or even years
– Depends on the body needs

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WBC Lifespan

• Platelets
– In blood are replaced every 10 days

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 General functions

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General Functions
Granulocytes
• Have vesicles containing biologically active
substances involved in inflammatory reaction
Basophils
• Contain histamine and heparin
– They release histamine when activated by T-
lymphocytes
• Important for immediate type of hypersensitivity

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General Functions
Eosinophils
• Attack parasites that are too large to be
– engulfed by phagocytosis
• Produce leukotrienes
– Involved in allergic reactions

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General Functions

Eosinophils
• Enter the tissues especially
– Mucous membrane of respiratory tract
– Lower urinary & GIT tract
• Essential for the provision of mucous membrane
immunity
• Circulating levels of eosinophils
– Elevated in patients with allergic diseases

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Functions (neutrophils)

Neutrophils
• Seek out and ingest and kill bacteria
– First line defense against bacterial infections

• Invasion of the body by bacteria

– Triggers the inflammatory response
• Bone marrow
– Release large number of neutrophils

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Functions (neutrophils)

Bacterial products interact with plasma factors

• Produce agents that attract neutrophils to the
infected area
– Chemotaxis agents
• Bacterial or viral toxin
• Products of inflammed tissue

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 Functions (neutrophils)

Other plasma factors act on the bacteria surface

• To make them tasty for the phagocytes
– Process known as opsonization
• Coated with Immunoglobulins IgG or complement proteins

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Functions (neutrophils)
Coated bacteria then
• Bind to receptors on the neutrophil cell membrane
– Trigger increase motor activity response in phagocytes
– Prompt ingestion of bacteria by endocytosis
– Phagocytosis

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Functions (neutrophils)
By exocytosis
• Neutrophil granules discharge their contents
into
– Phagocytic vacuoles
• The granules contain
– Various proteases
– Antimicrobial antibiotics (defensin)

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Functions (neutrophils)

NADPH oxidase enzyme is activated

• To produce toxic O2 metabolites (Free radicals)
– Superoxide (02-)
– H2O2
• Powerful bactericidal activity
Myeloperoxidase enzyme catalyze reaction
• To form hypochlorite
– Exceedingly bactericidal

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Functions (neutrophils)

• Neutrophil also contain elastase

• Attack collagen
– Help in the destruction of invading organism

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Functions (neutrophils)

Neutrophils also release

• Thromboxanes
– Vasoconstrictors
– Platelets aggregator
• Leukotrienes
– Increase vascular permeability
– Attract other neutrophils

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From: Robbins and Cotran Pathologic Basis of Diseases
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Monocytes

• Enter the circulation

• After transit time in the circulation
– Enter the tissues
• Transformed into macrophages
• Tissue macrophage include
– Kupffer cells in liver
– Pulmonary alveolar macrophages
– Microglia in the brain

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Tissue Microphages

Macrophages become activated by

• Lymphokines from T-lymphocytes
– Migrate in response to chemotactic stimuli
• Engulf and kill bacteria in similar manner that occur in neutrophils
Macrophages play key role in immunity by secreting
different substances including
• Factors that affect lymphocytes and other cells
• Prostaglandins
• Clot promoting factors

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Basophils & Mast Cells

• Basophils in circulation are similar to mast

cells found in tissues
– Beneath epithelial surfaces
• Both basophils and mast cells liberate
– Heparin into circulation
• Anticoagulant

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Basophils & Mast Cells

• They also liberate

– Histamine, serotonin, bradykinins
• They have IgE receptors on the cell membrane
– When IgE coated antigen binds to their cell
membrane
• Release of histamine, bradykinin
serotonin
– Causing allergic reaction

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Regulation of Production of WBC

• Both production of RBC and WBC

– Are regulated with great precision
• Production of granulocytes
– Rapidly increases during infection
• Proliferation and maturation of cells that enter
the blood from bone marrow
– Regulated by glycoprotein growth factors or
hormones

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Regulation of Production of WBC

• These growth factors causes

• PHSC to proliferate into committed progenitor
cells
– Committed stem cells to proliferate and
mature

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Role of Macrophages

• Inflammation activate
macrophages to release
multiple growth factors
– Granulocyte-monocyte
colony stimulating factor
– Granulocyte – colony
stimulating factor
– Interleukin 1
– Monocyte –colony
stimulating factor
– Tumor necrosis factor

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Factors Regulating Haematopoiesis

• Granulocytes
macrophage CSF (GM-
CSF)
– From T cells, monocytes,
endothelial cells,
fibroblasts
• Cause increased
production of
– Neutrophils,
Monocytes, Eosinophils,
Megakaryocytes, RBC

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Factors Regulating Haematopoiesis

• Monocyte- CSF (M-CSF)

– From macrophages,
fibroblasts, endothelial
cells
• Cause increase
production of monocytes

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Factors Regulating Haematopoiesis

• Interleukin 1 (IL-1)
– From macrophages,
endothelial cells,
fibroblasts
• Cause increased
production of
– Neutrophils, basophils,
Monocytes, Eosinophils,
Megakaryocytes, RBC

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Factors Regulating Haematopoiesis

• Interleukin 3 (IL-3)
• From T cells
– Cause increased production of
• Neutrophils, basophils, Monocytes, Eosinophils,
Megakaryocytes, RBC
• Interleukin 4 (IL-4)
• From T cells
– Cause increased production of
• Basophils

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Factors Regulating haematopiesis
• Interleukin 5 (IL-5)
• From T cells
– Cause increased production of
• Eosinophils
• Interleukin 6 (IL-6)
• From macrophages, endothelial cells, fibroblasts
– Cause increased production of
• Neutrophils, basophils, Monocytes, Eosinophils,
Megakaryocytes, RBC

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 Myeloblast

IL-1, IL6, IL3

GM-CSF, IL-5 Pro-Myeloblast IL-4

GM-CSF, M-CSF

GM-CSF, G-CSF
GM-CSF

Neutrophil Eosinophil Basophil Megakaryocyte

myelocyte myelocyte myelocyte

Neutrophil Eosinophil Basophil monocyte

Platelets

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