LEUKOCYTE DEVELOPMENT, KINETICS, AND FUNCTIONS Flashcards by Kyra Catedral

• Relatively colorless compared to red blood cells.

LEUKOCYTES (WBC)

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• CLASSIFIED ACCORDING TO:

• Granularity
• Nuclear Segmentation
• Function

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Function of WBCs

mediating immunity

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• 3 Body Compartments

Bone Marrow
Peripheral Blood
Tissues

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• TYPICAL REFERENCE INTERVAL:

4.5 X 10^9/L - 11.5 x 10^9/L

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WBCs with granules and different staining characteristics

GRANULOCYTES

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• - granules containing basic proteins
• - granules that are acidic
• - granules that react with both acid and basic stains

EOSINOPHIL

BASOPHIL

NEUTROPHILS

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MONONUCLEAR CELLS
• Categorized into (2)

monocytes and lymphocytes

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• Cells have nuclei that are not segmented

Mononuclear cells

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NEUTROPHIL: DEVELOPMENT

• Occurs in the______
• __________
• Share common progenitor with monocytes
• Distinct from eosinophil and basophil

bone marrow

GRANULOCYTE MONOCYTE PROGENITOR (GMP)

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3 POOLS OF DEVELOPING NEUTROPHILS IN THE BM

Stem cell pool
Proliferation (mitotic) pool
Maturation (storage) pool

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Stem cell pool

Proliferation pool

Maturation pool

HSC

CMP
GMP
Myeloblast
Promyelocyte
Myelocyte

Metamyelocyte
Band
Neutrophil

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Neutrophil

• Earliest morphologically identifiable granulocyte precursor

MYELOBLAST

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Neutrophil

• Thin rim of basophilic cytoplasm
• No granules
• Lacy chromatin pattern
• Two or more nucleoi

MYELOBLAST

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MYELOBLAST

• High N:C ratio (____)
•_____ um
•_____ in the normal bone marrow
• NOT FOUND IN PERIPHERAL BLOOD

6:1

14-20um

0-3%

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MYELOBLAST

• Fine nuclear chromatin and slightly basiphilic cytoplasm
• 2-4 visible nucleoli
• Have NO VISIBLE GRANULES

TYPE I MYELOBLAST

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MYELOBLAST

• Presence of less than twenty primary granules in the Cytoplasm

TYPE II MYELOBLAST

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MYELOBLAST

• Darker chromatin and more purple cytoplasm
• More than twenty granules in the cytoplasm

TYPE III MYELOBLAST

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PROMYELOCYTE
• Comprise____ of the nucleated cells in the BM
•____ um in dm

1-5%

16-25

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• NUCLEUS: round to oval and is often eccentric
• Paranuclear halo or “hof” = seen in normal but not in malignant cells
• Chromatin clumping maybe visible
• 1-3 nucleoli can be seen but maybe obscurec by the granules

PROMYELOCYTE

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• CYTOPLASM: basophilic and full of primary (azurophilic) granules
• 1st in a series of granules to be produced
• NOT SEEN IN PERIPHERAL BLOOD

PROMYELOCYTE

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• Make up 6-17% of the nucleated cells in the BM
• FINAL STAGE OF MITOSIS OCCURS
• Primary granules => ceases
• Secondary granules(specific) => begins to manufacture

MYELOCYTE

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Divided to 2 myelocyte
•_______ - look similar to promyelocytes
• Patches of grainy pale pink cytoplasm
• SECONDARY GRANULES begin to be evident “DAWN OF NEUTROPHILIA”

• _______- smaller the promyelocyte (15-18 um)
• NUCLEUS: more heterochromatin
• Nucleoli: difficult to see

Early myelocyte

Late myelocyte

• Constitute 3-20% of nucleated marrow cells
• NO LONGER CAPABLE OF DIVISION
• SIZE: 14-16 um
• NUCLEUS: indented

• Chromatin - increasingly clumped
• Nucleoli - Absent
• TERTIARY GRANULES - begin during this stage

METAMYELOCYTE

• CYTOPLASM: contains very little residual RNA • Little to no basophilia • ***SEEN IN PERIPHERAL BLOOD OF NEWBORNS***

METAMYELOCYTE

• Make up 9-32% of nucleated marrow cells • 0-5% of the nucleated peripheral blood cells • Pale - blue pink cytoplasm • RNA is absent • Curved, band-shaped nucleus which has not developed a threadlike filaments • ***TERTIARY GRANULES: continue to be formed***

BAND CELL or STAB CELL

• ***SECRETORY GRANULES*** (aka: secretory vesicles) - begin to form • ***Greatest source of variation and discrepancy*** in leukocyte morphology

BAND CELL or STAB CELL

MATURE NEUTROPHIL •_________ granules • Course, clumped chromatin •_____ lobes •_____ um

Pink to rose-violet specific 3-5 9-15

MATURE NEUTROPHIL • LIFESPAN:____ •_____ in the bone marrow • IN THE PERIPHERAL BLOOD •_____(Relative Count) •________ (absolute count)

9-10 days 7-30% 50-70% 2.3-8.1x10^9/L

KINETICS • BONE MARROW • Transit time from HSC to myeloblast • Not measured • Transit time from myeloblast to myelocyte •_____ • Transit time through maturation pool •______

6 days 4-6 days

NEUTROPHIL KINETICS • BLOOD •_________ • Freely floating in the bloodstream •__________ • Adhering to the blood vessel wall • Stays for____ hours in the blood • TISSUE • Dies after doing its function

CIRCULATING NEUTROPHIL POOL MARGINAL NEUTROPHIL POOL 7

NEUTROPHIL KINETICS • EXTRAVASATION

• ROLLING • ADHESION • CRAWLING • TRANSMIGRATION

NEUTROPHIL GRANULES PRIMARY SECONDARY TERTIARY

PRIMARY GRANULES Myeloperoxidase Elastase Proteinase-3 Cathepsin G Defensins SECONDARY GRANULES Collagenase Lactoferrin NADPH oxidase TERTIARY GRANULES Gelatinase Plasminogen activator Acid hydrolase

NEUTROPHIL FUNCTIONS • INNATE IMMUNE SYSTEM • PHAGOCYTOSIS (4)

• Recognition and Attachment • Ingestion • Oxygen-Dependent Killing • Oxygen Independent Killing

FUNCTIONS • INNATE IMMUNE SYSTEN • PHAGOCYTOSIS • Phagocyte receptors bind to certain foreign molecular patterns and opsonins such as antibodies and complement components • Pseudopodia formation to engulf the pathogen • Respiratory burst through production of H202 (primary ROS) and hypochlorite (secondary ROS) • Other enzymes

• Recognition and Attachment • Ingestion • Oxygen-Dependent Killing • Oxygen Independent Killing

NET

NEUTROPHIL EXTRACELLULAR TRAPS

EOSINOPHIL • EOSINOPHIL DEVELOPMENT Cytokines

• IL-3,IL-5 and GM-CSF • TF(GATA-1, PU.1 and c/EBP) • GATA-1 and PU.1=MBP

EOSINOPHIL _______ • Microscopically the same as neutrophil •_______ • Microscopically the same as neutrophil promyelocyte but cytochemically different because of ***CHARCOT-LEYDEN CRYSTAL PROTEIN***

MYELOBLAST PROMYELOCYTE

EOSINOPHIL •_______ • Same nuclear characteristics with neutrophil myelocyte but contains large, pale, reddish-orange secondary granules •________ • Secondary granules increase in number • Secretory vesicles appear • Lipid bodies and small granules appear

MYELOCYTE METAMYELOCYTE AND BANDS

EOSINOPHIL • Make up 1-3% of nucleated cells in the bone marrow and peripheral blood • Usually with BILOBED NUCLEUS • Cytoplasm contains refractile, orange-red secondary granules

• MATURE EOSINOPHIL

EOSINOPHIL KINETICS • Transit time from last myelocytic division to release of mature eosinophils is______ • HALF LIFE:____ in the circulation • Survival in tissue:____ • Tissue destination: • Columnar epithelial surface in the respiratory, gastrointestinal and genitourinary tract

3.5 days 18 hours 2-5 days

EOSINOPHIL FUNCTION • EOSINOPHIL DEGRANULATION

• CLASSICAL EXOCYTOSIS • COMPOUND EXOCYTOSIS • PIECEMEAL DEGRANULATION • CYTOLYSIS

EOSINOPHIL FUNCTION • EOSINOPHIL DEGRANULATION • Granules fuse with plasma membrane • Granules fuse with each other then with the plasma membrane • Secretory vesicles remove specific protein from granules then fuse with plasma membrane • Eosinophil sombrero vesicles • Spilling of cellular contents • Second most common observed mode of degranulation

• CLASSICAL EXOCYTOSIS • COMPOUND EXOCYTOSIS • PIECEMEAL DEGRANULATION • CYTOLYSIS

EOSINOPHIL FUNCTIONS • Pleiotropic Multifunctional Leukocyte

• Allergy • Immune regulation • Adaptive Immunity • Acute and Chronic Allograft Rejection • Poor phagocytes • Plasma Cell Survival • Viral Infections • Platelet-eosinophil interaction

EOSINOPHIL FUNCTION • IgE response is physiological response to helminth infection • IgE axis evolved to counter metazoan parasites (worms and parasitic arthropods) which are too large to be phagocytosed • Allergy is misdirected anti-parasite response in hypersensitive people

• PARASITE KILLING

GRANULOCYTES BASOPHIL • BASOPHIL DEVELOPMENT Cytokines?? • Staging is not done

• IL-3, TSLP • IgE dependent (IL-3) • Non-IgE dependent (TSLP)

• Round to lobulated nuclei • Slightly condensed chromatin • Cytoplasm is blue and contains large blue-black secondary granules

• IMMATURE BASOPHIL

• Lobulated nucleus often obscured by granules • Clumped chromatin • Colorless cytoplasm with large blue-balck granules • Granules are water soluble

MATURE BASOPHIL

BASOPHIL KINETICS • POORLY understood of their rarity in the bone marrow and circulation • LIFE SPAN:_____ • IL 3 and 25 are anti-apoptotic

60 hours

Basophil Granules Secondary Granules

Histamine Platelet-activating factor Leukotriene Ca Interleukin-4 Interleukin-13 Vascular endothelial growth factor A Vascular endothelial growth factor B Heparan sulfate

FUNCTION • ALLERGY • Initiator of allergy • Adaptive Immunity • antigen presentation

BASOPHIL

• Poor Phagocytes • Angiogenesis • Helminthic Infection • Lymphocyte-mediated delayed hypersensitivity

BASOPHIL

GRANULOCYTES • Kit-Ligand • Microscopically ***similar to basophil (but bigger)*** • Progenitors originate in the bone marrow and spleen • Has ***longer life span than basophil***

MAST CELLS

Granulocyte Contains protease, peptidoglycan and cytokines in its granules

MAST CELL

MAST CELL FUNCTION

• Allergy • Inflammation • Antigen presentation • Anti-inflammatory • Immunosuppression • Immunologic gatekeepers