Hematology

WBCs 1 – Granulocytes
By Aya Mustafa
• WBC: mobile units of the body's protective system.
• Normal count is 4000-11,000 /µL
• Defend body against disease causing agents
• Have a nucleus
• Develop from stem cells in red bone marrow
Types:
• Granulocytes (Polymorphonuclear or "polys"):
• Neutrophils 60 %
• Eosinophils 2 %
• Basophils 0.4 %
• Agranulocytes (mononuclear):
• Lymphocytes 30 %
• Monocytes 5 %
Life span
• Granulocytes: 4-8 hours in blood, 4-5 days in tissues.
• Monocytes: 10-20 hours in blood, months in tissue (tissue macrophages)
• Lymphocytes live for weeks or months.
Granulocytes
1. Neutrophil ( polymorph)
• This cell has a characteristic dense nucleus consisting of between two
and five lobes, and a pale cytoplasm with an irregular outline
containing many fi ne pink – blue (azurophilic) or grey – blue granules.
• The lifespan of neutrophils in the blood is only 6 – 10 hours.
• Neutrophil precursors: These do not normally appear in normal
peripheral blood but are present in the marrow.
2. Monocytes :
• These are usually larger than other peripheral blood leucocytes and
possess a large central oval or indented nucleus with clumped chromatin.
The abundant cytoplasm stains blue and contains many fine vacuoles,
giving a ground - glass appearance.
• Cytoplasmic granules are also often present.
• The monocyte precursors in the marrow (monoblasts and promonocytes)
are difficult to distinguish from myeloblasts and monocytes.
• Monocytes spend only a short time in the marrow and, after circulating for
20 – 40 hours, leave the blood to enter the tissues where they mature and
carry out their principal functions.
3. Eosinophils:
• Th ese cells are similar to neutrophils, except that the cytoplasmic
granules are coarser and more deeply red staining and there are
rarely more than three nuclear lobes.
• The blood transit time for eosinophils is longer than for neutrophils.
They enter inflammatory exudates and have a special role in allergic
responses, defense against parasites and removal of fi brin formed
during inflammation.
4.Basophils:
Th ese are only occasionally seen in normal peripheral blood.
They have many dark cytoplasmic granules which overlie the nucleus
and contain heparin and histamine In the tissues they become mast
cells.
They have immunoglobulin E (IgE) attachment sites and their
degranulation is associated with histamine release
Control of granulopoiesis: myeloid growth
factors
• The granulocyte series arises from bone marrow progenitor cells
which are increasingly specialized. Many growth factors are involved
in this maturation process including interleukin - 1 (IL - 1), IL - 3, IL - 5
(for eosinophils), IL - 6, IL - 11, granulocyte – macrophage colony -
stimulating factor (GM - CSF), granulocyte CSF (G - CSF) and monocyte
CSF (M - CSF).
• Th e growth factors stimulate proliferation and differentiation and
also affect the function of the mature cells on which they act
Phagocytosis
• Definition: Cellular ingestion of the offending
agent.
• Most important function of neutrophils and
macrophages.
• Selective process.
• Phagocytosis is increased if:
• Surface of particle is rough.
• Lacks protective protein coat.
• Binding of antibodies to antigen (opsonization).
 Phagocytosis by neutrophils

• Also called polys: first line of defense in bacterial infections.

• Mature cells that can attack and destroy bacteria even in the
circulating blood.
• Attach to the particle and project pseudopodia around it→
an enclosed chamber that contains the phagocytized particle
which breaks away → free floating phagosome.
• Can phagocytize 3-20 bacteria before it dies.
2nd Year Medicine- IBLS Module May 2008
 Phagocytosis by monocytes
• Immature in blood (1-2 days)
• In tissues → mature and enlarge → tissue macrophages.
• Much more powerful phagocytes than neutrophils.
• Can phagocytize as many as 100 bacteria.
• Can engulf large particles e.g. malarial parasites.
• Can survive after phagocytosis for months.

2nd Year Medicine- IBLS Module May 2008

2nd Year Medicine- IBLS Module May 2008
Neutrophils and monocytes reach the site of
infection by the following mechanisms:

• They squeeze through the pores of the capillaries by

diapedesis.
• They move toward the site of infection by amoeboid
movement.
• Different chemicals released by microbes and
inflamed tissues attract neutrophils and
macrophages→ chemotaxis.
2nd Year Medicine- IBLS Module May 2008
2nd Year Medicine- IBLS Module May 2008
2nd Year Medicine- IBLS Module May 2008
Granulocytes abnormalities
1. Neutrophil leukocytosis An increase in circulating neutrophils to
levels greater than 7.5 × 10 9 /L is one of the most frequently observed
blood count changes;
2. The leukemoid reaction The leukemoid reaction is a reactive and
excessive leukocytosis usually characterized by the presence of
immature cells (e.g. myeloblasts, promyelocytes and myelocytes) in the
peripheral blood
3. Leucoerythroblastic reaction This is characterized by the presence of
erythroblast and granulocyte precursors in the blood (Fig 8.9 ). It is
caused by metastatic infiltration of the marrow or certain benign or
neoplastic blood disorders
4. Neutropenia Th e lower limit of the normal neutrophil count is 2.5 ×
10 9 /L.
• When the absolute neutrophil level falls below 0.5 × 10 9 /L the
patient is likely to have recurrent infections and when the count falls
to less than 0.2 × 10 9 /L the risks are very serious, particularly if
there is also a functional defect
5. Monocytosis A rise in blood monocyte count above 0.8 × 10 9 /L is
infrequent
6. Eosinophilic leukocytosis ( eosinophilia) Th e causes of an increase in
blood eosinophils above 0.4 × 10 9 /L.
• Eosinophilic leukocytosis is most frequently caused by allergic
diseases, parasites, skin diseases or drugs.
• if the eosinophil count is elevated ( > 1.5 × 10 9 /L) for over 6 months
and associated with tissue damage.
7. Basophil leukocytosis ( basophilia) An increase in blood basophils
above 0.1 × 10 9 /L is uncommon. The usual cause is a
myeloproliferative disorder such as chronic myeloid leukemia or
polycythemia
• Defects of function of neutrophils and monocytes may affect their
chemotaxis, phagocytosis or killing.
• Histiocytes are tissue macrophages derived from circulation
monocytes. They may form clonal diseases called Langerhans ’cell
histiocytosis which affect single or multiple organs.
• The hemophagocytic syndrome involves destruction of red cells,
granulocytes and platelets by tissue macrophages.
• Lysosomal storage diseases are caused by inherited defects in the
enzymes responsible for breakdown of glycolipids. Gaucher ’ s disease
is caused by glucocerebrosidase deficiency and is associated with
accumulation of glycolipids in the reticuloendothelial system with
splenomegaly, pancytopenia and bone lesions causing the main
clinical manifestations
Hematology
WBCs 2 – Lymphocytes
By Aya Mustafa
Lymphocytes
• Lymphocytes are the immunologically competent cells that assist the
phagocytes in defense of the body against infection and other foreign
invasion .
• Two unique features characteristic of the immune system are the
ability to generate antigenic specificity and the phenomenon of
immunological memory
• the bone marrow and thymus are the primary lymphoid organs in
which lymphocytes develop
• The secondary lymphoid organs in which specific immune responses
are generated are the lymph nodes, spleen and lymphoid tissues of
the alimentary and respiratory tracts.
Band T lymphocytes
• The immune response depends upon two types of lymphocytes, B
and T cells , which derive from the haemopoietic stem cell.
• B cells mature in the bone marrow and circulate in the peripheral
blood until they undergo recognition of antigen.
• The B - cell receptor is membrane - bound immunoglobulin and after
activation this is secreted as free soluble immunoglobulin. At this
point they mature into memory B cells or plasma cells. The latter
home to the bone marrow and have a characteristic morphology with
an eccentric round nucleus with a ‘ clock - face ’ chromatin pattern
and strongly basophilic cytoplasm.
• T cells develop from cells that have migrated to the thymus where
they differentiate into mature T cells during passage from the cortex
to the medulla
• During this process, self - reactive T cells are deleted (negative
selection) whereas T cells with some specificity for host human
leucocyte antigen (HLA) molecules are selected (positive selection).
The mature helper cells express CD4 and cytotoxic cells express CD8.
• The cells also express one of two T - cell antigen receptor
heterodimers, αβ ( > 90%) or γδ ( < 10%), and recognize antigen only
when it is presented at a cell surface.
Natural killer cells
• Natural killer (NK) cells are cytotoxic CD8 + cells that lack the T - cell
receptor (TCR). They are large cells with cytoplasmic granules and
typically express surface molecules CD16, CD56 and CD57.
• NK cells are designed to kill target cells that have a low level of
expression of HLA class I molecules such as may occur during viral
infection or on a malignant cell.
• NK cells do this by displaying a number of receptors for HLA
molecules on their surface. When HLA is expressed on the target cell
these deliver an inhibitory signal into the NK cell
Lymphocyte circulation
• Lymphocytes in the peripheral blood migrate through post - capillary
venules into the substance of the lymph nodes or into the spleen or bone
marrow.
• T cells home to the perifollicular zones of the cortical areas of lymph nodes
(paracortical areas) and to the periarteriolar sheaths surrounding the
central arterioles of the spleen.
• B cells selectively accumulate in follicles of the lymph nodes and spleen.
• Lymphocytes return to the peripheral blood via the efferent lymphatic
stream and the thoracic duct.
• CD4 helper cells predominate in normal peripheral blood and germinal
centres, but in the marrow and gut the major T - cell subpopulation is CD8
positive.
Immunoglobulins
• These are a group of proteins produced by plasma cells and B
lymphocytes that bind to antigen.
• five subclasses or isotypes: G (IgG), IgA, IgM, IgD and IgE.
• The same cell can switch from IgM to IgG, or to IgA or IgE synthesis
Complement immune response
• is a cascade of plasma proteins that can either lyse cells or coat
(opsonize) them so they are phagocytosed.
• The complement sequence consists of nine major components – C1,
C2 , The most abundant and pivotal protein is C3.
• The early (opsonizing) stages leading to coating of the cells with C3b
can occur by two different pathways:
1 The classic pathway usually activated by IgG or IgM coating of cells
2 The alternate pathway , which is more rapid and activated by IgA
• Macrophages and neutrophils have C3b receptors and they phagocytose C3b -
coated cells.
• One of the most striking features of the immune system is its capacity to produce
a highly specific response. For both T and B cells this specificity is achieved by the
presence of a particular receptor on the lymphocyte surface.
• Naive (or virgin) B and T lymphocytes which leave the bone marrow and thymus
are resting cells that are not in cell division
• Specialized macrophages called dendritic cells process antigens before presenting
them to B and T lymphocytes – they are therefore known as antigen - presenting
cells.
• T and B cells undergo clonal expansion if they meet an APC that is presenting an
antigen that can trigger their antigen receptor molecules. At this stage,
lymphocytes may develop into effector cells (such as plasma cells or cytotoxic T
cells) or memory cells
• T and B cells undergo clonal expansion if they meet an APC that is presenting an
antigen that can trigger their antigen receptor molecules
• At this stage, lymphocytes may develop into effector cells (such as plasma cells or
cytotoxic T cells) or memory cells.
• DCs can be matured by a variety of stimuli such as inflammatory cytokines –
tumour necrosis factor - α (TNF - α ) and interleukin - 1 (IL - 1)
Lymphocytosis
• Lymphocytosis often occurs in infants and young children in response
to infections that produce a neutrophil reaction in adults.
Infectious mononucleosis : This is caused by primary infection with EBV
• Th e disease is characterized by a lymphocytosis caused by clonal
expansions of T cells reacting against B lymphocytes infected with
EBV
• Lymphopenia :
Lymphopenia may occur in severe bone marrow failure.
• Immunodeficiency:
A large number of inherited or acquired defects in any of the
components of the immune system can cause an impaired immune
response with increased susceptibility to infection.
Lymphadenopathy :