B3.038 Hematopoiesis Prework Flashcards
why do many neoplasms begin early in a myeloid cell’s lineage?
cells are only actively dividing prior to -blast stage
after -blast stage, less division and more purely morphological changes
what growth factors stimulate differentiation of pluripotent stem cells?
SCF
IL-6
Flt3L
what is meant by fundamental dichotomy?
different disorders/diseases arise from trilineage myeloid stem cells vs. lymphoid stem cells
what happens to the % cellularity of bone marrow after birth?
declines slowly as a patient ages
what organs are involved in hematopoiesis prior to birth?
yolk sac
spleen
liver
bone marrow
what organs are involved in hematopoiesis after birth?
just bone marrow
different locations within the body
what is extramedullary hematopoiesis?
reactivation of hematopoiesis outside bone marrow due to insufficient bone marrow reserve
what can cause extramedullary hematopoiesis to occur?
bone marrow damage
myeloid neoplasm
extreme demand from bone marrow
what are some sites of extramedullary hematopoiesis?
liver
spleen
lymph nodes
soft tissue
what makes up bone marrow?
sinusoids, 50% hematopoietic cells, 50% fat
myeloid:erythroid = 3:1
cells : fat = 1:1 or 100-age = % cells
what are precursors of platelets?
megakaryocytes
what morphological features differentiate neutrophils?
segmented (lobular) nucleus
granules in cytoplasm
primary neutrophilic granule contents
myeloperoxidase lysozyme defensins acid hydrolases neutral proteases
secondary neutrophilic granule contents
lysozyme collagenase lactoferrin plasminogen activator histamine alkaline phosphatase
function of eosinophils
involved in anti-parasitic functions, allergic reactions, and chronic inflammation
eosinophilic granule contents
peroxidase major basic protein eosinophilic cationic protein eosinophil derived neurotoxin last 3: cytotoxic for helminths and protozoans
function of basophils
involved in IgE mediated allergic reactions
basophilic granule contents
histamine
chondroitin sulfate
tryptase
functions of monocytes
cytokine production phagocytosis antigen presentation removal of old or damaged erythrocytes / iron recycling clearance of neoplastic or foreign cells
small monocytic granule contents
lysosomal enzymes
give an overview of the morphological features of T lymphocytes
mature in thymus rearrange TCR genes express CD2, CD3, CD5 CD4+ (helper/inducer) CD8+ (suppressor/cytotoxic)
give an overview of the morphological features of B lymphocytes
mature in bone marrow
rearrange Ig genes
express CD19, CD20, HLA-DR, and surface Ig
mature into plasma cells
what cell type is classified as a lymphocyte along w B and T cells?
NK cells
describe the structure of the TCR
made up of an alpha and beta OR gamma and delta chain pair
variable and constant region on each chain
describe the structure of an Ig
2 heavy chains- made up of G, A, D, E, or M
2 light chains - made up of k or L
V,D,J regions of heavy chain variable regions
all have different possible combos
describe the different developmental stages of B cells and their corresponding migration within the body
precursor B-lymphoblast : bone marrow
naïve B-cell: blood marrow primary follicle
ANTIGEN EXPOSURE
follicular B-blast > centroblat > centrocyte : germinal center
memory B-cell: marginal zone
plasma cell/ extrafollicular B blast: outside of bone marrow
what is Ig somatic mutation
occurs in antigenically stimulated B cells in both heavy and light chain hypervariable regions
- cells with increased affinity for antigen survive
- cells with decreased affinity for antigen removed through apoptosis
how can you detect Ig somatic mutations?
amplification and sequencing of V region and comparison with known germline V genes
cells from germinal center portion of B cell maturation
prognostic significance in some B cell neoplasms
