Leukocyte Development, Kinetics, and Function Flashcards
A bacterial infection will most likely cause a dramatic increase in which cell line?
Neutrophils
3 forms of cell production
- Erythropoiesis
- Leukopoiesis
- Megakaryopoiesis
2 forms of leukopoiesis
- Myelopoiesis (monocytes/macrophages, eosinophils, basophils, and neutrophils)
- Lymphopoiesis
Where does hematopoiesis occur in a healthy adult?
BM
This theory suggests that all blood cells are derived from a single progenitor stem cell
Monophyletic Theory
Growth factors and ____ are terms that can be used interchangeably
Cytokines
These are a group of soluble proteins that modulate the functional activities of other cells; responsible for stimulation or inhibition of RBC maturation
Cytokines
An essential cytokine in the early stages of hematopoiesis b/c it stimulates cell proliferation
C-Kit; aka Stem Cell Factor (SCF)
Colony stimulating factors have ____ specificity and are active at ____ concentrations
High; Low
What does GM-csf stand for?
Granulocyte Macrophage
What does Meg-csf stand for?
Megakaryocyte
What does G-csf stand for?
Granulocyte
What does M-csf stand for?
Monocyte
How can colony stimulating factors be used in patient care?
To start production of different cell lines
Cytokines that exhibit multiple biologic activities including regulation of autoimmune and inflammatory reactions and hematopoiesis
Interleukins (IL)
2 examples of interleukins
- IL-3
- IL-6
Interleukin that controls production, differentiation, and function of granulocytes and macrophages
IL-3
Interleukin that stimulates myeloid and lymphoid cell lineages
IL-6
Programmed cell death
Apoptosis
Accidental cell death
Necrosis
As cell matures what two things happen?
- Decrease in cell size
- Decrease in N/C ratio
What specific changes occur in the nucleus during cell maturation?
- Loss of nucleoli
- Decrease in size
- Condensation of chromatin
- Possible shape changes
- Possible nucleus ejections
What specific changes occur in the cytoplasm during cell maturation?-
- Decrease in basophilia
- Increase in amount of cytoplasm
- Granules may appear
Therapeutic applications of cytokines
- Stimulate BM production of hematopoietic cells by using GM-csf, EPO, and interleukins
- Promote maturation of developmentally arrested cells
- Initiate apoptosis
- Slow proliferation
This cell has a nucleus w/ 2-5 nucleoli, moderate basophlia w/ less than 5 granules, and is not present in PB; these are increased in leukemia
Myeloblast
These cells have a round to oval nucleus with 1-3 or more nucleoli, slightly coarser chromatin than myeloblast, basophilic cytoplasm with few red to purple primary granules and no secondary granules; these are not present in peripheral blood under normal conditions
Promyelocyte
Primary granules are composed of ____
Myeloperoxidase (MPO)
Secondary granules are composed of ____
LAP
These cells have a round to oval nucleus that may have one flattened side, nucleoli not ususally visible, coarse chromatin, and is more condensed that promyelo; the cytoplasm is slightly basophilic but starting to turn pink due to granules; these are not present in peripheral blood under normal conditions
Myelocyte
This cell has an indented nucleus, nucleoli are not visible, and chromatin is coarse and clumped; cytoplasm is pink; not found in peripheral blood under normal conditions
Metamyelocyte
This cell has a band shaped nucleus which is constricted but no threadlike filament; cytoplasm is pink; and ______% are found in peripheral blood
Band; 0-6%
This cell’s nucleus has 2-5 lobes connected by thin filaments and is found in the peripheral blood as _______%
Seg; 50-70%
Two neutrophil pools in the BM
- Proliferation (mitotic) pool
- Maturation (storage) pool
A left shift causes cells to be pushed out of the ____ pool first
Maturation
____ stimulates neutrophils in the BM to enter the PB
G-csf
Loosely attached to the endothelial lining of small capillaries or sequestered in the spleen or liver
Marginal pool
Collected in venipuncture in the peripheral blood; neutrophils are split equally b/w the marginal and this pool
Circulating pool
Neutrophils that have migrated into tissues from the PB in response to infection or inflammation
TIssue pool
Part of the innate immune system, no memory against re-exposure
- Major function: phagocytosis of the bacteria
Neutrophils
Neutrophil recruitment to the inflammatory site
Chemotaxis
5 steps of the leukocyte adhesion cascade
- Capture
- Rolling
- Slow rolling
- Firm adhesion
- Transmigration
In this step, chemoattractant activates endothelial cells; draws leukocytes to a position closer to the endothelium of the blood vessel
Capture
In this step, the WBCs transiently adhere to the endothelium and begin to roll
Rolling
Cell adhesion molecule; expressed on the surface of activated endothelial cells
P-selectin
This step requires expression of E-selectin on endothelium and CD18 integrin in lipid bilayer of WBC
Slow rolling
Receptors that mediate attachement b/w a cell and the tissue
Integrins
Process where adhered WBCs escape from the interior of the blood vessel through the endothelium
Transmigration
Half life of neutrophils in the blood is ____ hours before they’re removed by the RES
7
Eosinophil maturation mirrors ____ maturaiton stages
Neutrophil
Ag presenting cells; regulate immune response by controlling mast cell function; increased in parasitic infections; allergic disorders such as asthma and food allergies
Eosinophils
Believed to share a common progenitor cell with eosinophils derived from the CMP; usually only divided in two phases, mature and immature
Basophils
These cells mature in the tissues and are NOT leukocytes; similar to basophils but bigger
Mast cells
What is the main difference between basophils and mast cells if they BOTH originate in the bone marrow and BOTH are major players in allergic inflammation?
Basophils mature in the BM and mast cells mature in the tissue
They share a GMP with neutrophils; originate in the bone marrow; storage pool is in the spleen but like neutrophils they have a circulating and marginal pool
Monocytes
3 stages of monocytes
- Monoblasts (indistinguishable from myelocytes)
- Promonocytes
- Monocytes
Innate immunity (phagocytosis), adaptive immunity (Ag presenting to T and B cells), and housekeeping (remove debris, storage pool of iron for erythropoiesis)
Function of monocyte/macrophage
The storage pool of iron for erythroipoiesis or the erythroblastic island are also known as what?
Nurse cells or sideroblasts
What two types of immunity do lymphocytes provide?
- Innate immunity
- Adaptive immunity
These do not need to be presented with antigen and are part of the innate immunity of lymps
NK cells
These cells are presented with an antigen and have to respond; one provides cellular immunity and one provides humoral immunity
Cellular = T cells Humoral = B cells
B cells develop in the BM and have what 3 stages?
- Pro-B
- Pre-B
- Immature B
What is the primary function of B cells?
Ab production (and can play a role in Ag presentation to T cells)
After immature B cells leave the BM and travel to LNs they’re presented w/ Ag and either become memory B cells or effector B cells, also known as what?
Plasma cells
These develop in the thymus and regulate immune response
T cells
What are the 3 stages of T cell maturation?
- Pro-T
- Pre-T
- Immature T
These develop in the thymus and bone marrow; their PRIMARY function is killing tumor cells and virus-infected cells without prior sensitization because they are a part of the innate immune system
NK cells
BM process of RBC production
Erythropoiesis
Process by which WBCs form and develop in the BM and LNs
Leukopoiesis
Production of BM and of all cells that arise form it; basically all blood cells
Myelopoiesis
Formation and production of lymphs, predominately in the LNs
Lymphopoiesis
Production and development of megakaryocytes, the precursors to platelets in the BM
Megakaryopoiesis
Immune response initiated and mediated by cytokines, NKs, and macrophages; the mechanism of acquired immunity characterized by the dominant role of T lymphocytes
Cellular immunity
Nonspecific immunity (damage host cells and tissues)
Innate immunity
Immune response mediated by B lymphocytes, which produce circulating Abs in reaction to infectious organisms and other foreign Ags
Humoral immunity
After monocytes enter tissues, they can mature into ____, ____, or ____
Macrophages; osteoclasts; dendritic cells
How does movement of neutrophils from one pool to another affect lab results?
- If neutrophils are moving from the circulating pool to the marginal pool → leukocytopenia in the circulating pool
- If patient is exhibiting hepatosplenomegaly → leukocytosis in the marginal pool
