Lecture 5 - WBC Flashcards
What are the 3 types of white blood cells
Granulocytes - neutrophils, eosinophils, basophils (polymorphonuclear)
Monocytes (mononuclear)
Lymphocytes - B cells, T cells, NK cells (mononuclear)
Describe neutrophils
Pale staining cytoplasm and pink granules (lysozyme & superoxide’s) - segmented nucleus (2-5 lobes)
Describe how neutrophils are phagocytic
Recruited by chemokines (IL-8) - receptors on surface, secrete antimicrobials & neutrophil extracellular traps - die 24-72 hrs in tissue
What is neutrophilia and neutropenia
Neutrophilia - bacterial infection, inflammation, drug-induced, malignancy (myeloid leukaemia)
Neutropenia (too few) - infection, severe bacterial, immunosuppression, ethnic, increased risk
Describe eosinophils
Segmented nucleus (2-3 lobes)
large, refractile, red-orange granules
What does the presence of eosinophils mean
Type 1 hypersensitivity & immune defence against parasites (phagocytic)
Eosinophilia - allergic reactions, asthma, parasitic infections, malignant disease of myeloid cells
How long do eosinophils live
8-12 hrs in circulation
8-12 days in tissue
Describe Basophils
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)
When would basophils be present
Anaphylaxis
insect/snake venom
blood cancers
Describe monocytes
Large cells
kidney shaped nucleus & blue-grey cytoplasm
Differentiate into macrophages in tissue (20-40 hrs in circulation)
What is monocytosis
Chronic inflammation or infection - malignancy (myelodysplastic syndrome)
What happens when monocytes differentiate to macrophages
become phagocytic
produce pro-inflammatory cytokines
present antigen to T cells
Initiate healing
Describe lymphocytes
pleomorphic, non-segmented nucleus and variable cytoplasm - T (60-80%) & B cells (15-30%)
Can’t differentiate type of lymphocyte from morphology
Describe lymphocytosis and lymphopenia
Lymphocytosis - normal in children - many infections, malignancy
Lymphopenia - drug therapy (immunosuppressive & cytotoxic agents), AIDS, severe stress
Describe Natural Killer cells
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
What are cluster of differentiation markers
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
What are WBC diseases
Leukopenia - deficiency
Proliferative disorders - reactive (infection), malignant (myeloid, lymphoid neoplasms)
What are malignant diseases
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
Describe blood cancers
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
Describe lymphoid neoplasms
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)
Describe myeloid neoplasms
Acute myeloid leukaemia’s - immature rapidly dividing blasts
Myeloproliferative neoplasms - mature cells
Myelodysplastic syndrome -abnormal cells
Describe acute leukaemia
Rapid growth of blast cells
Intensive chemotherapy & stem cell transplant - variable prognosis (excellent in children)
Describe lymphoblastic leukaemia
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
describe chronic myeloid leukaemia
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
Describe CML morphology & clinical features
Splenomegaly - infiltrated with blood cells
Peak age (25-45) - treatment with tyrosine kinase inhibitors
Describe follicular lymphoma
Tumour from germinal centre B cells
Incurable but indolent - 30-50% transform to other (<1 yr)
Describe morphology of follicular lymphomas
Nodular growth pattern mixed population
centrocytes (sml. lymphoid cells with condensed chromatin & cleaved nuclear outlines)
Centroblasts - larger with nucleoli & more cytoplasm
What is the immunophenotype of follicular lymphomas
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
Describe clinical features of follicular lymphomas
Generalised lymphadenopathy, splenic white pulp & hepatic portal triads involved marrow involvement in 85% of cases
Supportive therapy - low dose chemo immunotherapy if symptomatic
