LEUKOCYTE DEVELOPMENT, KINETICS, AND FUNCTIONS Flashcards
book based
relatively colorless compared to red blood cells
Leukocytes
stain used to see leukocytes
Romanowky stain
what type of microscope is used to view wbc
Light microscope
a group of leukocytes whose cytoplasm is filled with granules with different staining characteristics and whose nuclei are segmented or lobulated.
Granulocytes
granules containing basic proteins that stain with acid stains such as eosin.
Eosinophils
granules that are acidic and stain with basic stains such as methylene blue.
Basophils
granules that react with both acid and basic stains, which gives them a pink to lavender color.
due to nuclear segmentation is quite prominent in mature neutrophils.
Polymorphonuclear cells
these cells have nuclei that are not segmented but are round, oval, indented, or folded.
Mononuclear cells
types of mononuclear cells
monocytes
lymphocytes
where does leukocyte develop
hematopoietic stem cell in bone marrow
Typical reference interval of leukocyte for adults
4.5 x 109/L to 11.5 x 109/L
movement of cells through developmental stages
Kinetics
present in peripheral blood in two forms according to whether the nucleus is segmented or still in a band shape.
Neutrophils
a common progenitor with monocytes and distinct
from eosinophils and basophils.
Granulocyte monocyte progenitor (GMP)
major cytokine responsible for the stimulation of
neutrophil production.
Granulocyte colony – stimulating factor (G-CSF)
Three pools of developing neutrophils in the bone
marrow
Stem cell pool
Proliferating pool
Maturation pool
pool that is capable of self-renewal and
differentiation.
Stem cell pool
pool that cells that are dividing and includes common myeloid progenitors.
Proliferating pool
pool that undergoes nuclear maturation that form the bone marrow reserve and at are available for release.
Maturation pool
make up 0% to 3% of the nucleated cells in the bone marrow and measure 14-20 um in diameter
Myeloblasts
has a high nucleus-to-cytoplasm ratio of 8:1 to 4:1. No visible granules when observed under light microscopy with Romanowsky stain.
Type I myeloblast
shows the presence of dispersed primary granules in the cytoplasm (granules does not exceed 20 per cell).
Type II myeloblast
have a darker chromatin and a more purple cytoplasm, and they contain more than 20 granules that do not obscure the nucleus. Rare in normal bone marrows, but they can be seen in certain types of acute myeloid leukemias.
Type III myeloblasts
omprise 1% to 5% of the nucleated cells in the bone marrow. The nucleus is round and is often eccentric. These granules are the first in a series of granules to be produced during neutrophil maturation.
Promyelocytes
make up 6% to 17% of the nucleated cells in the bone marrow and are the final stage in which cell division occurs. The production of primary granules ceases and the cell begins to manufacture secondary neutrophil granules.
Myelocytes
also known as “dawn of neutrophilia” look very similar to the promyelocytes in size and nuclear
characteristics except that patches of grainy pale pink cytoplasm representing secondary granules.
Early myelocytes
slowly spread through the cell until its cytoplasm is
more lavender-pink than blue.
Secondary neutrophilic granules
smaller than promyelocytes, and the nucleus has
considerably more heterochromatin. Nucleoli are difficult to see by light microscopy.
Late myelocytes
constitute 3% to 20% of nucleated marrow cells. The cells are no longer capable of division and the major morphologic change is in the shape of the nucleus. Synthesis of tertiary granules may begin during this stage.
Metamyelocytes
make up 9% to 32% of nucleated marrow cells and 0% to 5% of the nucleated peripheral blood cells. All evidence of RNA is absent, and tertiary granules continue to be formed during this stage.
Bands
the middle ground states that when doubt exists, an elevated band count was thought to be useful in the diagnosis of patients with infections.
Segmented neutrophil
recommends that bands should be included within
the neutrophil count and not reported as a separate
category.
Clinical and Laboratory Standards Institute (CLSI)
make up 7% to30% of nucleated cells in the bone marrow. Secretory granules continue to be formed during this stage. The only morphologic difference between segmented neutrophils and bands is the presence of between 2-5 nuclear lobes connected by thread-like filaments.
Segmented neutrophils
Involves the movement of neutrophils and neutrophil precursors between the different pools in the bone marrow, peripheral blood, and tissues.
NEUTROPHIL KINETICS
loosely localized to the walls of capillaries in tissues such as the liver, spleen, and lung
Marginated neutrophil pool (MNP)
The half-life of neutrophils in the blood
7 hours
significant importance in allowing neutrophils to marginate as well as exit the blood and enter the tissues by a process known as diapedesis.
Integrins and selectin
are removed by macrophages in the spleen, bone marrow, and liver
apoptosis
Spontaneous neutrophil apoptosis is regulated by pro- and antiapoptotic members
B-cell lymphoma 2 family
Activation is facilitated by the rolling of neutrophils on endothelium surfaces
Chemokines
tend to prolong the neutrophil’s life span through antiapoptotic signals
Myeloid cell leukemia-1 and myeloperoxidase
trigger the death and phagocytosis of neutrophils
macrophage-1 antigen
major function of neutrophils
phagocytosis and destruction of foreign material and
microorganisms
three functions of neutrophils
- Phagocytosis and destruction of foreign
materials - generation of NETs
- Secretory function
degrade the extracellular matrix and act as chemotactic agents for extravasation and migration of additional neutrophils to the site of inflammation.
Tertiary granules
extracellular thread-like structures believed to represent chains of nucleosomes from unfolded
nuclear chromatin material. able to trap and kill
gram-positive and gram-negative bacteria as well as
fungi
NETs - neutrophil extracellular nets
unique form of neutrophil cell death that
results in the release of NETs.
NETosis
make up 1% to 3% of nucleated cells in the bone marrow. An absolute number of up to 0.4 x 109 /L in the peripheral blood.
eosinophils
critical for eosinophil growth and survival.
IL-5 and IL-33
characterized by the presence of large, pale, reddish orange secondary granules, along with azure granules in blue cytoplasm.
Eosinophil myelocytes
can be identified cytochemically because of the presence of Charcot-Leyden crystal protein in their primary granules
Eosinophilic promyelocytes
resemble their neutrophil counterparts with respect to their nuclear shape.
Eosinophil metamyelocytes and bands
display a bilobed nucleus. Their cytoplasm contains characteristic refractile, orange-red secondary granules.
Mature eosinophils
The time from the last myelocyte mitotic division to
the emergence of mature eosinophils from the marrow
3.5 days
Third type of granule is generated
secretory granule
eosinophils circulating half life
18hrs
Survival time of eosinophils in human tissues
2 to 5 days
secretory vesicles remove specific proteins from the secondary granules
Piecemeal degranulation
granules fuse together within the eosinophil before fusing with the plasma membrane.
Compound exocytosis
granules move to the plasma membrane, fuse with the plasma membrane, and empty their contents into the extracellular space
Classical exocytosis
full of a large number of previously synthesized proteins, including cytokines, chemokines, growth factors, and cationic proteins.
Eosinophil granules
true leukocytes because they mature in the bone
marrow and circulate in the blood as mature cells
with granules
basophils
evidently capable of synthesizing granule proteins based on activation signals.
Mature basophils
occurs when extracellular intact granules
are deposited during cell lysis.
Cytolysis
precursors leave the bone marrow and use the blood as a transit system to gain access to the tissues where they mature.
mast cell
life span of basophils
60 hours
can induce basophils to produce and release
retinoic acid, a regulator of immune and resident cells in allergic diseases.
Mast cells
the effectors of IgE-mediated chronic allergic inflammation, basophils function as initiators of
the allergic inflammation through the release of
preformed cytokines.
Mast cells
basophils are activated by what interleukins, antiapoptotic pathways are initiated that prolong the basophil lifespan.
IL-3 and IL-25
play a role in angiogenesis through the expression of
vascular endothelial growth factor (VEGF) and its
receptors
mast cells and basophils
They are tissue effector cells of allergic responses and
inflammatory reactions.
MAST CELLS
major cytokine responsible for the growth and
differentiation of monocytes.
Macrophage colony-stimulating factor (M-CSF)
Morphologic stages of monocyte development
Monoblasts
Promonocytes
Monocytes
exists in normal bone marrow are very rare and are difficult to distinguish from myeloblasts based on morphology.
Monoblasts
12 to 18 um in diameter, and their nucleus is slightly indented or folded
Promonocytes
they tend to stick to and spread out on glass or plastic.slightly immature cells whose ultimate goal is to enter the tissues and mature into macrophages, osteoclasts, or dendritic cells.
Monocytes
Monocytes remain in the circulation approximately
3 days
survive far longer than tissue neutrophils.
Resident macrophage
life span measured in hours.
Inflammatory macrophages
recognize a wide range of bacterial pathogens by means of pattern recognition receptors (Toll-like receptors) that stimulate inflammatory cytokine production and phagocytosis. they can phagocytize foreign organisms or materials that have been coated with antibodies or complement components.
Innate immunity
degrade antigen and present antigen fragments on their surfaces.
Adaptive immunity
most efficient and potent of the antigen-presenting cells.
Dendritic cells
they develop in the thymus
T cells
removal of debris and dead cells at sites of infection or tissue damage.
Housekeeping
3 major group of lymphocytes
▪ T cells
▪ B cells
▪ NK cells
make up a small percentage of lymphocytes
and are part of innate immunity
NK cells
play a major role in adaptive immunity
T and B cells
Antibody-producing lymphocytes; they develop in the bone marrow
B lymphocytes
develop in both the bone marrow and the thymus
NK cells
development occurs in the bone marrow and thymus
Antigen - independent lymphocyte
development occurs in the spleen, lymph nodes, tonsils, and mucosa-associated lymphoid tissue such as the Peyer’s patches in the intestinal wall
Antigen-dependent lymphocyte
T lymphocytes develop initially in the thymus—a
lymphoepithelial organ located in
upper mediastinum
develop initially in the bone marrow and go through three stages known as pro-B, pre-B, and immature B cells.
B lymphocytes
produce cytokines that regulate a variety of T cell and antigen presenting cell functions.
B cells
essential for antibody production.they have a role in antigen presentation to T cells and may be necessary for optimal CD4 activation.
B lymphocytes
can be divided into CD4% T cells and CD+ T cells
T lymphocytes
mediate immune responses against intracellular pathogens
TH1 cell
mediate host defense against extracellular parasites, including helminths. They are also important in the induction of asthma and other allergic diseases.
TH2 cells
involved in the immune responses against extracellular bacteria and fungi.
TH17 cells
play a role in maintaining self-tolerance by regulating immune responses
Treg cells
capable of killing target cells by secreting granules containing granzyme and perforin or by activating apoptotic pathways in the target cell.
CD8+ effector lymphocytes
part of innate immunity and are capable of killing certain tumor cells and virus-infected cells without prior sensitization. Modulate the functions of other cells, including macrophages and T cells
NK lymphocytes
major cytokine responsible for mast cell
maturation and differentiation
KIT ligand
