Lecture 5 - WBC

Question 1

What are the 3 types of white blood cells

Answer 1

Granulocytes - neutrophils, eosinophils, basophils (polymorphonuclear)
Monocytes (mononuclear)
Lymphocytes - B cells, T cells, NK cells (mononuclear)

Question 2

Describe neutrophils

Answer 2

Pale staining cytoplasm and pink granules (lysozyme & superoxide’s) - segmented nucleus (2-5 lobes)

Question 3

Describe how neutrophils are phagocytic

Answer 3

Recruited by chemokines (IL-8) - receptors on surface, secrete antimicrobials & neutrophil extracellular traps - die 24-72 hrs in tissue

Question 4

What is neutrophilia and neutropenia

Answer 4

Neutrophilia - bacterial infection, inflammation, drug-induced, malignancy (myeloid leukaemia)
Neutropenia (too few) - infection, severe bacterial, immunosuppression, ethnic, increased risk

Question 5

Describe eosinophils

Answer 5

Segmented nucleus (2-3 lobes)
large, refractile, red-orange granules

Question 6

What does the presence of eosinophils mean

Answer 6

Type 1 hypersensitivity & immune defence against parasites (phagocytic)
Eosinophilia - allergic reactions, asthma, parasitic infections, malignant disease of myeloid cells

Question 7

How long do eosinophils live

Answer 7

8-12 hrs in circulation
8-12 days in tissue

Question 8

Describe Basophils

Answer 8

Bi-lobed nucleus & dark purple granules
Contains histamines, leukotrienes, heparin, vasoactive mediators
Weakly phagocytic (inflammatory & allergic)
APC to drive Th2 response, can bind IgE (rare)

Question 9

When would basophils be present

Answer 9

Anaphylaxis
insect/snake venom
blood cancers

Question 10

Describe monocytes

Answer 10

Large cells
kidney shaped nucleus & blue-grey cytoplasm
Differentiate into macrophages in tissue (20-40 hrs in circulation)

Question 11

What is monocytosis

Answer 11

Chronic inflammation or infection - malignancy (myelodysplastic syndrome)

Question 12

What happens when monocytes differentiate to macrophages

Answer 12

become phagocytic
produce pro-inflammatory cytokines
present antigen to T cells
Initiate healing

Question 13

Describe lymphocytes

Answer 13

pleomorphic, non-segmented nucleus and variable cytoplasm - T (60-80%) & B cells (15-30%)
Can’t differentiate type of lymphocyte from morphology

Question 14

Describe lymphocytosis and lymphopenia

Answer 14

Lymphocytosis - normal in children - many infections, malignancy
Lymphopenia - drug therapy (immunosuppressive & cytotoxic agents), AIDS, severe stress

Question 15

Describe Natural Killer cells

Answer 15

Large granular lymphocytes
Activated by low MHC-1/activating receptors, induced apoptosis in target cells
See antigen presented on CD1d - produce large amounts of cytokines

Question 16

What are cluster of differentiation markers

Answer 16

CD34 stem cells
CD45 common WBC marker
CD19 and CD20 B cells
CD3 T cells (CD4 helper and CD8 cytotoxic)
CD16 NK cells
CD14 monocytes

Question 17

What are WBC diseases

Answer 17

Leukopenia - deficiency
Proliferative disorders - reactive (infection), malignant (myeloid, lymphoid neoplasms)

Question 18

What are malignant diseases

Answer 18

Normal cells respond to normal regulatory signal for growth, maturation & death
Uncontrolled growth & fail to die - clonal proliferation
When large enough can replace normal marrow & infiltrate into other tissues, replacing & destroying normal cells

Question 19

Describe blood cancers

Answer 19

Malignant - grow & accumulate in marrow (depend on type of cell affected)
Results in bone marrow failure - replacement of normal marrow spaces and reduced num. of normal cells

Question 20

Describe lymphoid neoplasms

Answer 20

Acute lymphoblastic leukaemia - proliferation of immune, rapidly growing lymphoid cells in bone marrow
Chromic lymphocytic leukaemia - proliferation of mature lymphoid cells in BM
Lymphomas - solid tumours of proliferating lymphocytes (lymph nodes, spleen, blood)

Question 21

Describe myeloid neoplasms

Answer 21

Acute myeloid leukaemia’s - immature rapidly dividing blasts
Myeloproliferative neoplasms - mature cells
Myelodysplastic syndrome -abnormal cells

Question 22

Describe acute leukaemia

Answer 22

Rapid growth of blast cells
Intensive chemotherapy & stem cell transplant - variable prognosis (excellent in children)

Question 23

Describe lymphoblastic leukaemia

Answer 23

Most common in children - immature B or T cells
Cells arrested at early stage of B-cell development - express markers associated with early B cells - CD10 common acute lymphoblastic leukaemia antigen

Question 24

describe chronic myeloid leukaemia

Answer 24

Presence of chimeric BCR-ABL gene - translocation between BC gene on Chr 22 and ABL gene on Chr 9 (Philadelphia chromosome)
Constitutive expression of BCR-ABL tyrosine kinase, drivers proliferation of myeloid precursors

Question 25

Describe CML morphology & clinical features

Answer 25

Splenomegaly - infiltrated with blood cells
Peak age (25-45) - treatment with tyrosine kinase inhibitors

Question 26

Describe follicular lymphoma

Answer 26

Tumour from germinal centre B cells
Incurable but indolent - 30-50% transform to other (<1 yr)

Question 27

Describe morphology of follicular lymphomas

Answer 27

Nodular growth pattern mixed population
centrocytes (sml. lymphoid cells with condensed chromatin & cleaved nuclear outlines)
Centroblasts - larger with nucleoli & more cytoplasm

Question 28

What is the immunophenotype of follicular lymphomas

Answer 28

Resembles germinal centre B cells
Over 90% BCL2+ (antibodies) - oncoprotein antagonizes apoptosis - not normally expressed on follicular B cells, translocation created BCL-2-igH fusion gene, promotes survival of lymphoma cells

Question 29

Describe clinical features of follicular lymphomas

Answer 29

Generalised lymphadenopathy, splenic white pulp & hepatic portal triads involved marrow involvement in 85% of cases
Supportive therapy - low dose chemo immunotherapy if symptomatic