LEUKOCYTES

Jul 16, 2022 Leukocytes 1

 Leukocytes (WBC)
• Mobile unit of body’s defense system
– Formed in the bone marrow
• Granulocytes, monocytes, few lymphocytes
– Lymph tissue
• Lymphocytes &plasma cells
• After formation
– Transported in blood
• Different parts of the body where they are to be used

Jul 16, 2022 Leukocytes 2

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

Jul 16, 2022 Leukocytes 3

 Characteristics of Leukocytes
• Characteristics
• Polymorpho nuclear cells
– Have abundant membrane bound intracellular
granules
• Hence (granulocytes)
– Also they have multilobed nucleus
• Polymorphs

Jul 16, 2022 Leukocytes 4

 Characteristics of Leukocytes
• Granules of one group
– Take up red dye eosin
• Polymorpho nuclear eosinophils
– eosinophils

• Granules of the second group

– Take up blue dye “basic dye”
• Polymorpho nuclear basophils
– Basophils

Jul 16, 2022 Leukocytes 5

 Characteristics of Leukocytes
• Granules of third group
– Have little affinity for either dye
• Polymorphonuclear neutrophils
– Neutrophils

• Monocytes, lymphocytes(plasma cells) &

platelets
– Have no granule in their cytoplasm
• Agranulocytes

Jul 16, 2022 Leukocytes 6

 Number & Distribution
• Adults have about 4,000 – 11,000 wbc/L of blood
• Normal % of different types
– Neutrophils 50 – 70%
– Eosinophils 1 – 4%
– Basophils 0.1 – 0.4%
– Monocytes 2 – 8%
– Lymphocytes 20 – 40%
• Total platelets 250,00 – 300,000/ L of blood

Jul 16, 2022 Leukocytes 7

 Genesis of Blood Cells
Erythrocytes

CFU -E Granulocytes
CFU-B
Monocytes
PHSC CFU -Spl

CFU-GM Macrophages
Megakaryocytes

Platelets
CFU-M
PHSC T - Lymphocytes
Lymphoid
B - Lymphocytes
stem cell
Jul 16, 2022 Leukocytes 8
 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

Jul 16, 2022 Leukocytes 9

 Myeloblast

Pro-Myeloblast

Neutrophil Eosinophil Basophil Megakaryocyte

myelocyte myelocyte myelocyte

Neutrophil Eosinophil Basophil monocyte

Platelets

Jul 16, 2022 Leukocytes 10

 Lymphoblast

Bursal equiv tissue Thymus

B-Lymphocyte T-Lymphocyte

Jul 16, 2022 Leukocytes 11

 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

Jul 16, 2022 Leukocytes 12

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

Jul 16, 2022 Leukocytes 13

 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

• Platelets
– In blood are replaced every 10 days

Jul 16, 2022 Leukocytes 14

 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

Jul 16, 2022 Leukocytes 15

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

Jul 16, 2022 Leukocytes 16

 Functions (neutrophils)
• Neutrophils
– Seek out and ingest and kill bacteria
• First line defense against bacterial infections
– Invasion of the body by bacterial
– Triggers the inflammatory response
• Bone marrow
– Release large number of neutrophils

Jul 16, 2022 Leukocytes 17

 Functions (neutrophils)
• Bacterial products interact with plasma factors
– Produce agents that attract neutrophils to the infected
area
• Chemotaxis agents
• Other plasma factors act on the bacteria surface
– To make them tasty for the phagocytes
• Process known as opsonization
– Coated with Immunoglobulins IgG

Jul 16, 2022 Leukocytes 18

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

Bacteria
engulfed

Jul 16, 2022 Leukocytes 19

 Functions(neutrophils)
Intracellular
granules
• By exocytosis
Invading – Neutrophil granules
bacteria
discharge their contents
Bacteria
engulfed
into
• Phagocytic vacuoles
Phagocytic – The granules contain
vacuole
• Various proteases
• Antimicrobial antibiotics
(defensin)

Jul 16, 2022 Leukocytes 20

 Functions (neutrophils)
Intracellular
granules
• NADPH oxidase
Invading
bacteria
enzyme is activated
Bacteria
– To produce toxic O2
engulfed metabolites
• Free radicals
Phagocytic
vacuole
• H2O2
– Powerful bactericidal
activity

Jul 16, 2022 Leukocytes 21

 Functions(neutrophils)
Intracellular
granules • Neutrophil also contain elastase
– Attack collagen
Invading • Help in the destruction of
bacteria
invading organism
Bacteria • Neutrophils also release
engulfed
– Thromboxanes
• Vasoconstrictors
Phagocytic • Platelets aggregator
vacuole
– Leukotrienes
• Increase vascular permeability
• Attract other neutrophils

Jul 16, 2022 Leukocytes 22

 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

Jul 16, 2022 Leukocytes 23

 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
• Factors that affect lymphocytes and other cells
• Prostaglandins
• Clot promoting factors

Jul 16, 2022 Leukocytes 24

 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

Jul 16, 2022 Leukocytes 25

 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

Jul 16, 2022 Leukocytes 26

 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

Jul 16, 2022 Leukocytes 27

 Regulation of Production of WBC
• These growth factors causes
– PHSC to proliferate into committed progenitor
cells
– Committed stem cells to proliferate and mature

Jul 16, 2022 Leukocytes 28

Factors Regulating Haematopoiesis
• Erythropoietin
– From kidneys, Kupffer cells liver
• Cause increased production of RBCs
• Colony Stimulating Factor
• Granulocyte CSF (G-CSF)
– From monocytes, fibroblasts, endothelia cells
• Cause increased production of Neutrophils

Jul 16, 2022 Leukocytes 29

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

Jul 16, 2022 Leukocytes 30

Factors Regulating Haematopoiesis
• Macrophage CSF (M-CSF)
– From monocytes, fibroblasts, endothelial cells
• Cause increase production of monocytes
• Interleukin 1 (IL-1)
– From macrophages, endothelial cells, fibroblasts
• Cause increased production of
– Neutrophils, basophils, Monocytes, Eosinophils,
Megakaryocytes, RBC

Jul 16, 2022 Leukocytes 31

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

Jul 16, 2022 Leukocytes 32

 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

Jul 16, 2022 Leukocytes 33

 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

Jul 16, 2022 Leukocytes 34

• LEUKEMIA • LEUKOPENIA
• Over production of • Under production
WBC of WBC

A clinical condition known as leukopenia, in which the bone

marrow produces very few white blood cells, occasionally occurs.
This leaves the body unprotected against many bacteria and
other agents that might invade the tissues.

Jul 16, 2022 Leukocytes 35

Uncontrolled production of white blood cells can be caused by cancerous mutation of a myelogenous or
lymphogenous cell. This causes leukemia, which is usually characterized by greatly increased numbers of
abnormal white blood cells in the circulating blood.

Types of Leukemia

Leukemias are divided into two general types: lymphocytic leukemias and myelogenous leukemias. The
lymphocytic leukemias are caused by cancerous production of lymphoid cells, usually beginning in a lymph node
or other lymphocytic tissue and spreading to other areas of the body. The second type of leukemia,
myelogenous leukemia, begins by cancerous production of young myelogenous cells in the bone marrow and
then spreads throughout the body so that white blood cells are produced in many extramedullary tissues-
especially in the lymph nodes, spleen, and liver.

Jul 16, 2022 Leukocytes 36