Leukopoiesis Flashcards
Reference Range for WBC
4.5 - 11.5X10^9
Leukocyte distribution
neutrophils=50-70%
lymphocytes=18-42%
monocytes= 2-11%
eosinophils = 1-3%
basophils = 0-2%
Neutrophil Maturation (6 stages)
myeloblast
promyelocyte
myelocyte
metamyelocyte
band neutrophil
segmented neutrophil
Myeloblast
14-20 microns
N/C ratio 4:1
nucleoli open chromatin
no granules
CD34, CD33, CD13, CD38
Promyelocyte
14-20 microns
N/C 3:1 nucleoli
open chromatin basophilic in color
PRIMARY GRANULES
CD33 CD38
Myelocyte
12-18 microns
N/C 2:1 or 1:1
often eccentric nucleus
APPEARANCE OF 2nd (specific) GRANULES primary granules may be present
Metamyelocyte
10-18 microns
N/C 1:1
INDENTED, KIDNEY BEAN nucleus no nucleoli clumped chromatin pink cytoplasm secondary granules beginning of tertiary granules
Band Neutrophil
‘stab cell’, nonsegmented
N/C 1:1
curved nucleus VERY CLUMPED chromatin pink cytoplasm secondary granules and tertiary granules
5% in peripheral blood
Segmented Neutrophil
polymorphonuclear leukocyte, PMN, seg, polys
distinct lobes 2-5 with a thin nuclear filament
no nucleoli
densely packed chromatin secondary & tertiary granules and secretory vesicles
CD15 CD16 CD11b CD18
50-70% in peripheral blood
Neutrophil Lifespan
BM-differentiation, proliferation, maturation (6-7 days)
PB- circulate for a few hours
Tissues- perform their function of host defense (1-5 days in tissues)
Neutrophil Function
- adherence
- migration
- phagocytosis
- bacterial killing
Neutrophil adherence
free flowing in the blood -> endothelium cell is activated by cytokines signal activates neutrophil activated neutrophil rolls to specific endothelium cell moves through blood vessel wall (pseudo pods)
neutrophil migration
chemotaxis- crawling movement gradient of chemicals directs movement neutrophil shape alteration
neutrophil phagocytosis
Ingestion of foreign particles requires large amount of energy
Neutrophil Bacterial killing
antimicrobial granules fuse with the phagosome
oxygen-dependent/oxidative
oxygen-independent/nonoxidative
NETS
Oxygen-dependent/oxidative bacterial killing
phagocytosis with ‘respiratory burst’:
hydrogen peroxide
superoxide anion
hydroxyl radicals
myeloperoxidase
Oxygen-independent/nonoxidative bacterial killing
release of granules:
myeloperoxidase
lysozyme (hydrolyze cell wall of some bacteria)
lactoferrin (directly bactericidal)
hydrolases (digests microbes)
NETs
neutrophil extra cellular traps neutrophils release granule proteins and chromatin that forms fibers that bind the bacteria kills bacteria
Eosinophils General
develop from CFU-GEMM and CFU-Eo
same 6 stages of maturation
distinguish from neutrophils by prominent granules (orange/pink)
granules will not obscure nucleus
Eosinophil granules
major basic protein (MBP)
eosinophil peroxidase (EPO)
eosinophil cationic protein (ECP)
eosinophil-derived neurotoxin (EDN)
Major basic protein (MBP)
eosinophil granule cytotoxic for protozoa and helminth parasites
release of histamine & heparin
eosinophil cationic protein (ECP)
release of histamine & heparin enhances mucus production in the bronchi
eosinophil-derived neurotoxin (EDN)
inhibits T cell reponses
eosinophil peroxidase (EPO)
cytotoxic for tumor & host cells
stimulates histamine relase
Eosinophil function
host defense against helminth parasites associated with pro-inflammatory cells active in allergic diseases, parasitic infections, chronic inflammation
Basophils General/ Maturation
develop from CFU-GEMM & CFU-Baso
basophilic blast
promyelocyte
basophilic myelocyte
basophilic metamyelocyte
basophilic band basophil
Basophil
Basophil Granules
large, dark blue/purple/black various sizes, unevenly distributed obscure the nucleus!
contain HISTAMINE as well as heparin, platelet activating factor, leukotriene C4, IL-4, IL-13
Mast cells
resident TISSUE ‘basophils’ live from weeks to months similar function to basophil
Basophil Function
poorly understood
mediators in inflammatory response (especially in hypersensitivity) receptors for IgE that cross linked with Ag result in granule release enzymes released are:
vasoactive
bronchoconstrictive
chemotactic
Hypersensitivity steps
- Ag is presented to T helper cells
- stimulates B cell production= produce large # of IgE
- IgE attach to mast cells and basophils = sensitization phase
- exposed to Ag for a 2nd time= activates mast/baso cells and release histamine & cytokines
Monocytes Maturation
CFU-GEMM & CFU-GM
monoblast
promonocyte
monocyte
Monoblast
12-20 microns
N/C ratio 4:1
round/folded/indented nucleus
fine chromatin
vacuoles may be present
no granules
abundant cytoplasm
Promonocyte
12-20 microns
3:1 or 2:1 ratio
irregular/folded nucleus
fine chromatin
vacuoles may be present/granules may be present
Monocyte
12-20 microns
2:1 1:1 ratio
ABNORMAL NUCLEUS
fine chromatin
abundant blue/grey cytoplasm VACUOLES
‘ground glass’ appearance
Macrophages General
matured monocytes in the tissues: cellular enlargement 15-80 microns
round nucleus/ nucleoli appear many vacuoles distinct
granules long lived!
Tissue specific Macrophage names
liver- Kupffer cells
Lungs- alveolar macrophages
skin-langerhans cells
brain-microglial cells
Monocyte/ Macrophage function
ingest & kill microorganisms/cellular debris & foreign matter
phagocytosis is much quicker than neutrophils
antigen presenting cells
Antigen-independent lymphopoeisis
primary lymphoid tissue T & B cells have not reacted with Ag
exit primary lymph tissue
migrate to 2nd lymphoid tissue
antigen-dependent lymphopoeisis
begins with recognition of & interaction with antigens results in formation of:
T cytotoxic
T helper
T regulatory
plasma cells
memory cells
Primary Lymphoid tissue
bone
marrow
thymus
Secondary lymphoid tissue
lymph nodes
spleen
tonsils
Peyer’s patches (intestine)
T Lymphocyte maturation
develop initially in thymus
Pro T
Pre T
Immature T
leave thymus and migrate to 2ndary lymph organs to become activated by Ag
B Lymphocytes
initially develop in BM
Pro B
Pre B
Immature B
once activated -> produces B memory cells or plasma cells
NK cells
form of cytotoxic lymphocyte kill tumor cells & pathogen infected cells
CD16 CD56
Memory Cells
elicit a rapid 2ndary response arise from T & B blast cells
Lymphoblast
4:1 ratio
nucleoli
fine chromatin
no granules
Prolymphocyte
4:1 / 3:1 ratio
fewer nucleoli
slightly condensed chromatin
no/few granules
Lymphocyte categories
small and large lymphocyte
Small Lymphocyte
6-10 microns
4:1 or 3:1 ratio
deeply condensed chromatin
very small amount of cytoplasm
Large lymphocytes
11-18 microns
3:1 ratio
round/oval nucleus
variable nucleoli
colorless to blue cytoplasm
Reactive Lymphocytes
‘atypical’ ‘variant’ ‘transformed’ ‘stimulated’ ‘actiavted’
commonly seen in viral infections
enlarged nucleus
round/lobulated/folded/elongated/stretched irregular nucleus
chromatin patterns vary may have vacuoles
membrane may be indented by surrounding RBCs
Plasma Cells
B cells that have transformed to produce antibodies
not normally found in the PB
reside in lymph nodes, BM, GI tract
9-20 microns
ECCENTRIC nucleus
Clumped chromatin
DEEPLY BASOPHILIC CYTOPLASM
Flame Cells
morphological variation of plasma cell reddish/purple cytoplasm
red tinge due to glycoproteins
purplish due to ribosomes
Mott Cells
‘grape cells’ filled with globules containing Ig (russell bodies)
B cell precursor CD markers
CD10 CD19 CD21 CD22 CD24
T cell precursor CD markers
CD1 CD2 CD3 CD5 CD7
