White Blood Cells

Immune Effector cells include:

Granulocytes (polymorphonuclear leukocytes):
neutrophils, basophils, eosinophils
Agranulocytes: lymphocytes and monocytes

Immune response in the tissues is further amplified

by extravascular migration of these cells, as well as
tissue macrophages and mast cells all of these
together defense against tumors, bacterial, viral and
parasitic infections.
 Granulopoiesis
• Uncommitted stem cells
↓IL1,3,6 and GM-CSF,SCF
Myeloblast
↓ IL-5, GM-CSF, G-CSF, IL-3,SCF
Promyelocytes
Eosinophilic Neutrophilic Basophilic
↓ ↓ ↓
Myelocyte proper
Eosinophilic Neutrophilic Basophilic
↓ ↓ ↓
Meta-Myelocyte
Eosinophilic Neutrophilic Basophilic
↓ ↓ ↓
Band cell (Juvenile granulocytes)
↓ ↓ ↓
Eosinophil Neutrophil Basophil
neutrophil eosinophil basophil

monocyte lymphocyte
 Neutrophils, eosinophils, basophils,
monocytes
• White cells function in defence against
infection and other insults
• Neutrophils, eosinophils, basophils and
monocytes are phagocytes
• These phagocytic cells may have other
functions
• Changes in leucocyte numbers commonly
occur in disease
 Common clinical terms
Increased Decreased
Neutrophils Neutrophilia Neutropenia

Eosinophils Eosinophilia Eosinopenia

Basophils Basophilia Basopenia

Monocytes Monocytosis Monopenia

Lymphocytes Lymphocytosis Lymphopenia

1. Neutrophils
 NEUTROPHIL
• Also called polymorphonuclear granulocytes

• Cell size 10-14 micrometer

• Granules are violet or pink colored

• Plenty of fine granules

• Nucleus may have 2-7 lobes

• Percentage of cells in peripheral circulation is around 40-70 in adult.

• “Granulocyte” – each cell has 200-300 granules

• Differentiate in the marrow (5 days)

• Important growth factors: IL-3

• Half life in circulation is 6 hrs

• To maintain normal circulating blood level, it is necessary to produce 100 billion neutrophils per day.
 Neutrophils…
• Function for 5 days in tissues before death

• May be described in “pools” of neutrophils:

– marrow storage pool
– circulating pool
– marginated pool
– tissue pool
 Another typical neutrophil

Multilobulated
Granules nucleus
 Neutrophil function
• Protect against pyogenic (bacterial)
infection
• Move to site of infection by chemotaxis
• Phagocytose microorganisms
– facilitated if bacteria are coated with
antibodies (opsonisation)
– Formation of a phagosome
• Granules fuse with phagosome to kill
microorganisms
 How neutrophils kill bacteria
• Granules contain many cytotoxic substances
– degradative enzymes, lipases, proteases,
lysosymes
– cationic proteins, low pH, myeloperoxidase,
defensins, elastase, metalloproteases
• Granules produce antimicrobial oxygen
metabolites, eg
– superoxide (O2-)
– hydrogen peroxide (H2O2)
– Hydroxyl ions (OH-)
 NEUTROPHIL
• Neutrophils and monocytes provide non-specific or innate immunity and is directed against
bacteria only. They provide immunity by phagocytosis.
The steps in phagocytosis are;
• Margination: Attracted to endothelial surface by cell adhesion molecules (selectins)

• Diapedesis: leave the capillaries between endothelial cells

• Chemotaxis: component of complement system (C5a), leukotrienes, polypeptides from

lymphocytes, mast cells and basophils

• Opsonization: opsonins make bacteria tasty by coating bacteria by IgG and complement
proteins

• Phagocytosis: coated bacteria bind to G-protein coupled receptor on neutrophil cell

membrane

• Digestion: by exocytosis neutrophil granules discharge their contents such as proteases and
antimicrobial protein defensins, NADPH oxidase with production of toxic oxygen metabolites
and proteolytic enzymes

NADPH+ H++ 2O2→NADP+ + 2H+ + 2O2-

O2- + O2- + H+ → H2O2 +O2
 NEUTROPHIL
Neutrophilia:-
• Physiological: exercise, after meals, during pregnancy,
and parturition, physical and mental stress.
• Pathological: acute infections, tonsillitis, appendicitis,
pneumonia etc.

Neutropenia:-
• Physiological; rare and unusual.
• Pathological; typhoid, paratyphoid, viral influenza
depression of bone marrow.
 EOSINOPHIL
• Cell size 10-14 micrometer

• Nucleus purple color

• usually 85% bi-lobed and 15% trilobed

• Granules appear orange-red colored (light pink)

• Coarse and compactly packed granules

• Percentage of cells in peripheral circulation is around

1-6 in adult.
EOSINOPHIL
 Eosinophils
• Fully differentiated granulocytes

• IL-5 is most important growth factor, (IL3 and GM-CSF)

• Half life in blood 18 hrs before entering tissues

• Attracted to endothelial cells by selectins

• Liberate proteins, cytokines, chemokines that produce

inflammation

• Involved in defense against helminthic infections

• Involved in allergic reactions

 Functions
• Mild phagocytosis

• Collect at site of allergic reaction and limit their intensity by

degrading the effect of inflammatory mediators (histamine,
bradykinin) and inhibit mast cell or basophil degranulation

• Abundant in respiratory tract, GIT, UT, where they provide

local mucosal immunity

• Kill parasites by:

– Liberating hydrolytic enzymes from their granulles (modified
lysosymes)
– Very high peroxidase content (histaminase content is very high )
– Highly reactive oxygens
– Highly larvacidal polypeptide called major basic protein
 EOSINOPHIL
Eosinophilia:-
• Allergic conditions: bronchial asthma, urticaria,
hay fever
• Parasitic infestations: hookworm, filariasis, hydatid
disease
• Skin diseases: psoriasis

Eosinopenia:-
• aplastic anaemia,
• ACTH therapy
 BASOPHIL
• Cell size 10-14 micrometer

• Granules are dark blue colored

• Plenty of granules obscure boundary of the

nucleus.

• Nucleus is usually bi-lobed and since the staining

of nucleus and granules is same, most of the time
the nucleus gets masked.

• Percentage of cells in peripheral circulation is

around 0-1 in adult.
BASOPHIL
 Basophils and mast cells
• Least frequent granulocyte in the blood

• Basophils circulate in the blood, mast cells reside in the tissues

• Both mast cell and basophil release heparin into blood preventing blood
coagulation and activates hormone lipoprotein lipase which facilitates
absorption of TG after meals

• Express IgE receptor and participate in immediate type hypersensitivity

reactions

• Granules contain histamine, proteoglycan, bradykinin and serotonin, slow

reacting substance of anaphylaxis and number of lysosomal enzymes
causing local vascular and tissue reactions

• Granules also contain Eosinophil chemotactic factor of anaphylaxis (ECF-A)

• Important in pathogenesis of allergic disorders, asthma, hay fever, rhinitis

to severe anaphylatic shock

• Also important in protection against parasites and some bacteria

 MAST CELLS

• Mast cells are heavily granulated cells of the connective tissue that are
abundant in tissues that come into contact with the external environment,
such as beneath epithelial surfaces.
• Their granules contain proteoglycans, histamine, and many proteases.
• they degranulate when allergens bind to cell-bound IgE molecules directed
against them.
• They are involved in inflammatory responses initiated by immunoglobulins
IgE and IgG
• The inflammation combats invading parasites.
• involvement in acquired immunity,
• release TNF-α in response to bacterial products by an antibody-
independent mechanism, participating in the nonspecific innate immunity
that combats infections prior to the development of an adaptive immune
response
• mast cell degranulation produces clinical manifestations of allergy
including anaphylaxis.
 BASOPHIL
• Basophilia:-
– chronic myeloid leukemia,
– polycythemia,
– chickenpox,
– smallpox,
– TB,
– Influenza
• Basophilopenia:-
– occurs rarely as seen in severe septicemia or aplastic
anemia,
– after administration of glucocorticoids,
– drug induced reactions
 Leucopoiesis

• Pleuripotent stem cell → Lymphoblast

↓ GM-CSF, M-CSF ↓ IL-3
Monoblast Prolymphocyte
↓ ↓IL-2,4,7
Promonocyte Large lymphocyte
↓ ↓
Monocyte Lymphocytes
T cell B cell
 Monocytes and macrophages
• Monocytes in the blood stream are in transit

• Half-life in bloodstream is 1-2 days

• Enter tissues and differentiate into macrophages

• Have granules similar to neutrophils (secrete PG-E,

clot promoting factors)

• Respond to inflammation by chemotaxis

• Phagocytose microorganisms, particulate material,

tissue debris
Monocytes in blood
 Macrophages
• Important in resistance to many infectious
diseases, including
– tuberculosis, leishmaniasis,
– typhoid fever, systemic mycoses

• Resident tissue macrophages have

specialised functions and can live months

• Macrophases are activated by cytokines

released from T lymphocytes
Monocytes
become
tissue
macrophages
• Monocytosis
– Tuberculosis
– Syphilis
– leukaemias

• Monocytopenia
– Hypoplastic bone marrow
 Lymphocytes
• Essential for acquired immunity

• Formed in bone marrow, lymph node, thymus, spleen

• Processed in thymus (T cell) and bursal equivalent (B cell-fetal

liver and bone marrow)

• 2% in peripheral blood rest in lymphoid organs

• B-lymphocytes respond to antigen by transforming to plasma

cells and secreting specific antibody (humoral immunity)

• T-lymphocytes co-operate with antigen presenting cells in the

recognition of antigen

• Activated T-cells proliferate clonally (cell mediated immunity)

 Lymphocytes

Lymphocyte Activated lymphocyte

NK cell Plasma cell

(large granular lymphocyte)
 B- lymphocytes
• Develop in bone marrow
• Produce antibodies (immunoglobulins)
• Differentiate into antibody-secreting
plasma cells
• Memory cells circulate for many years and
“remember” the antigen – ready to
increase production on second exposure
 T- lymphocytes
• Start development in bone marrow and
complete it in the thymus
• Cell-mediated cytotoxic reactions and
delayed hypersensitivity reactions
• Cytokine production and helper activity
for B cells
 Types of T- lymphocytes
a. Cytotoxic (Tc)
– Also known as CD8 cells
– Kill infected body cells, destroys
transplanted cells
– Αβ T cell, γδ T cell and NK cells
b. HelperT (Th)
– Also known as CD4 cells
• Th1 secrete IL-2 and interferron gamma-
cellular immunity
• Th2 secrete IL-4,5- humoral immunity
 Natural killer (NK) cells

• Large granular lymphocytes

• Cytotoxic
• Do not need to be sensitised by
antigen
• Lymphocytosis
– Infections - acute viral (e.g. infectious
mononucleosis) and chronic (e.g. tuberculosis)
– Malignancy - chronic lymphocytic leukaemia, non
Hodgkin’s lymphoma, acute lymphoblastic
leukaemia
• Lymphopenia
– Hypoplastic bone marrow
– AIDs