B3.038 Hematopoiesis Prework

Question 1

why do many neoplasms begin early in a myeloid cell’s lineage?

Answer 1

cells are only actively dividing prior to -blast stage

after -blast stage, less division and more purely morphological changes

Question 2

what growth factors stimulate differentiation of pluripotent stem cells?

Answer 2

SCF
IL-6
Flt3L

Question 3

what is meant by fundamental dichotomy?

Answer 3

different disorders/diseases arise from trilineage myeloid stem cells vs. lymphoid stem cells

Question 4

what happens to the % cellularity of bone marrow after birth?

Answer 4

declines slowly as a patient ages

Question 5

what organs are involved in hematopoiesis prior to birth?

Answer 5

yolk sac
spleen
liver
bone marrow

Question 6

what organs are involved in hematopoiesis after birth?

Answer 6

just bone marrow

different locations within the body

Question 7

what is extramedullary hematopoiesis?

Answer 7

reactivation of hematopoiesis outside bone marrow due to insufficient bone marrow reserve

Question 8

what can cause extramedullary hematopoiesis to occur?

Answer 8

bone marrow damage
myeloid neoplasm
extreme demand from bone marrow

Question 9

what are some sites of extramedullary hematopoiesis?

Answer 9

liver
spleen
lymph nodes
soft tissue

Question 10

what makes up bone marrow?

Answer 10

sinusoids, 50% hematopoietic cells, 50% fat
myeloid:erythroid = 3:1
cells : fat = 1:1 or 100-age = % cells

Question 11

what are precursors of platelets?

Answer 11

megakaryocytes

Question 12

what morphological features differentiate neutrophils?

Answer 12

segmented (lobular) nucleus

granules in cytoplasm

Question 13

primary neutrophilic granule contents

Answer 13

myeloperoxidase
lysozyme
defensins
acid hydrolases
neutral proteases

Question 14

secondary neutrophilic granule contents

Answer 14

lysozyme
collagenase
lactoferrin
plasminogen activator
histamine
alkaline phosphatase

Question 15

function of eosinophils

Answer 15

involved in anti-parasitic functions, allergic reactions, and chronic inflammation

Question 16

eosinophilic granule contents

Answer 16

peroxidase
major basic protein
eosinophilic cationic protein
eosinophil derived neurotoxin
last 3: cytotoxic for helminths and protozoans

Question 17

function of basophils

Answer 17

involved in IgE mediated allergic reactions

Question 18

basophilic granule contents

Answer 18

histamine
chondroitin sulfate
tryptase

Question 19

functions of monocytes

Answer 19

cytokine production
phagocytosis
antigen presentation
removal of old or damaged erythrocytes / iron recycling
clearance of neoplastic or foreign cells

Question 20

small monocytic granule contents

Answer 20

lysosomal enzymes

Question 21

give an overview of the morphological features of T lymphocytes

Answer 21

mature in thymus
rearrange TCR genes
express CD2, CD3, CD5
CD4+ (helper/inducer)
CD8+ (suppressor/cytotoxic)

Question 22

give an overview of the morphological features of B lymphocytes

Answer 22

mature in bone marrow
rearrange Ig genes
express CD19, CD20, HLA-DR, and surface Ig
mature into plasma cells

Question 23

what cell type is classified as a lymphocyte along w B and T cells?

Answer 23

NK cells

Question 24

describe the structure of the TCR

Answer 24

made up of an alpha and beta OR gamma and delta chain pair

variable and constant region on each chain

Question 25

describe the structure of an Ig

Answer 25

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

Question 26

describe the different developmental stages of B cells and their corresponding migration within the body

Answer 26

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

Question 27

what is Ig somatic mutation

Answer 27

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

Question 28

how can you detect Ig somatic mutations?

Answer 28

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