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WHITE BLOOD CELLS

AND THEIR BENIGN


DISORDERS
DR. ASAAVA
WBC: DIFFERENTIAL COUNTS
• TWBC: 4-11X109/L
• Neutrophils: 2.5-7.5
• Lymphocytes: 1.5-3.5
• Monocytes 0.2-0.8
• Eosinophils 0.04-0.5
• Basophils 0.01-0.1
NEUTROPHILS: neutrophilia
• Bacterial infections
• Inflammation and tissue necrosis: myositis, vasculitis, MI, trauma
• Metabolic disorders: uraemia, eclampsia, acidosis, gout
• Neoplasms of all types
• Acute haemorrhage/haemolysis
• Steroid therapy
• Myeloproliferative disorders
• Growth factor treatment
Neutrophils: neutropaenia
• Congenital
• Acquired
• Drug induced
• Benign-race/familial
• Cyclical
• Immune: autoimmune, SLE, anaphylaxis
• Infections: viral-hepatitis, influenza, HIV, bacterial infections: typhoid, TB
• Bone marrow failure
• Splenomegaly
EOSINOPHILS: eosinophilia
• Allergy
• Parasitic disease
• Skin diseases
• Drug sensitivity
• Metastatic disease
Monocytosis
• Chronic bacterial infections: TB, brucellosis, typhoid
• Protozoal infections
• Hodgkin disease
Basophilia
• Chronic myeloid leukaemia
• Polycythaemia vera
LYMPHOCYTES
DR. ASAAVA
INTRODUCTION

• Aide phagocytes in immune defence against infection and


foreign substances
• Antigen specificity and immunologic memory
• Disease of lymphoid system and role of lymphocyte in
haematological system
PRIMARY LYMPHOCYTE FORMATION

• Post natal life: bone marrow and thymus primary lymphoid organs in which
lymphocytes develop
• Secondary lymphoid organs: organs in which immune responses develop; lymph
nodes, spleen, lymphoid tissues of respiratory system and alimentary canal
• Types: B and T lymphocytes
• B cells derived from bone marrow stem cells
• T cells derived from bone marrow stem cells and migrate to thymus to
differentiate into mature T cells by passage from cortex to medulla;
• Differentiation of T cells involves deletion/negative selection of self reactive T cells
and positive selection of T cells with specificity for human leucocyte antigen
molecules
• Mature helper T cells express CD4 and cytotoxic cells CD8 and each one of two
antigen receptor heterodimers: αβ >90% or γδ <10%
NATURAL KILLER CELLS

• Are cytotoxic T cell that lack T cell receptor


• Large with cytoplasmic granules, express CD16, CD56 AND CD57
• Kill cells with low level of expression of HLA class I molecules e.g.
in viral infection or malignant cells and also mediate ADCC
LYMPHOCYTE CIRCULATION

• In peripheral circulation they pass to lymph nodes and spleen


• T cells home perifollicular zones/paracortical zones of the lymph
nodes
• In spleen T cells occupy peri-arteriolar sheaths surrounding central
arterioles of the spleen
• B cells home to follicles of the spleen and lymphnode and in the
subcapsular zones of the periphery of the cortex and medullary zones
of lymph nodes
• In peripheral blood and germinal centres CD4 helper cells
predominate; CD8 T cells predominate in the BM and gut lymphoid
tissue
• Blood: T cells 80% lymphocytes; B cells 20% of lymphocytes
IMMUNOGLOBULINS

• Heterogenous group of proteins secreted by B cells and plasma cells upon


reaction with antigens
• Five subclasses: IgG, IgM, IgE, IgA, IgD
• IgG: 80% of serum immunoglobulins; IgG1, IgG2, IgG3, IgG4
• IgM ab produced first and cell later switches to IgG in response to Ag
• IgA is ab of secretions
• IgD and IgE involved in delayed type hypersensitivity
• Two heavy chains (γ in IgG, α in IgA, μ in IgM, δ in IgD and ε in IgE) and
two light chains κ or λ which found in all 5 immunoglobulins
• Specificity is due to highly variable regions in heavy and light chains
• Involved in defence but also in pathogenesis of haematological disorders
IMMUNOGLOBULINS

• Macroglobulinaemia and multiple myeloma: monoclonal population


of plasma cells and lymphocytes secrete specific Ig
• In some cases of multiple myeloma Bence Jones proteins
consisting of monoclonal light chains or light chain fragments (κ or
λ)
• Ig may bind to blood cells to cause a variety of immune disorders
(agglutination, lysis by complement or elimination by macrophages in
RES)
LYMPHOCYTOSIS
• Absolute increase in lymphocyte count above upper reference range
• Benign causes:
• Infections (acute/chronic)
• Thyrotoxicosis
• Malignant causes
• Acute lymphoblastic leukaemia
• Chronic lymphocytic leukaemia
• Non Hodgkin lymphoma
LYMPHOPAENIA
• Decrease in absolute lymphocyte count below lower reference limit
for age/sex/race of patient
• Bone marrow failure
• Irradiation
• Immune deficiency e.g. HIV
• Immune suppression therapy
• Corticosteroid therapy
Haematologic effects of HIV
• Cytopaenia/pancytopaenia: bone marrow suppression (anaemia,
thrombocytopaenia-immune, marrow dysfunction; neutropaenia,
lymphopaenia
• Bone marrow effects
• Normocellular/normal
• Hypocellular-suppression-OI(TB, cryptococcosis, HIV, leishmaniasis,
histoplasmosis), fibrosis, malignancy (metastatic ca, lymphoma,
leukaemia), drugs (AZT, ganciclovir, pentamidine, septrin)
• Hypercellular: plasma cells, lymphocytes
LYMPHADENOPATHY
• Enlargement of lymph nodes
• Discrete/matted
• Localised/generalised
• Clinical history, examination, age, duration, pain, consistency
• Assess size of liver and spleen
• Localised: inflammatory or malignant-LN drains area in which
malignancy is located
LYMPHADENOPATHY: ANCILLARY LAB
TESTS
• FBC/CBC
• PBF
• ESR/C-RP
• Ab/PCR for viral illness: CMV
• Toxoplasmosis
• HIV test
• Lymph node biopsy and FNA
LOCALISED LYMPHADENOPATHY
• Local infection: bacterial, viral, TB
• Malignancy: lymphoma (HL, NHL); metastatic ca-20
GENERALISED LYMPHADENOPATHY
• Infection: viral(EBV, hepatitis), bacterial (TB, salmonella), fungal
(histoplasmosis), protozoal (toxoplasmosis)
• Non-infectious: inflammatory: RA, SLE, connective tissue disease)
• Malignancy: leukaemia, lymphoma, Waldenströms
macroglobulinaemia
• Reaction to drugs and chemicals
Splenomegaly
• Haematological: CML, CLL, ALL, AML, LYMPHOMA, haemolytic
anaemia
• Portal hypertension
• Systemic disease:
• Infections: acute(septicaemia, typhoid, ), chronic (TB, brucellosis,
malaria)

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