- Granulocytes - Mononuclear cells

Leukocyte Development, Kinetics, and Functions Flashcards by Janaine Balagot Pesiao

Two categories

Granulocytes
Mononuclear cells

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are a group of leukocytes whose cytoplasm is filled with granules with differing staining characteristics and whose nuclei are segmented or lobulated.

Granulocytes

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categorized into MONOCYTES and LYMPHOCYTES. These cells have nuclei that are not segmented but are round, oval, indented, or folded.

Mononuclear cells

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The number of circulating leukocytes vary depending on:

• Sexandage
• Activity andethnicity
• Timeofday
• Differs according to whether or not the leukocytes are reacting to stress, being consumed, orbeing destroyed, and whetheror not they are being produced by the bone marrowinsufficient numbers.

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NormalValues:

Adult:
Children:
Newborn:

Adult: 3.6– 10.6 x 10³/µL or 3.6 x10.6x10⁹/L Children: 5.0– 17.0 x 10³/µL or 5.0–17.0x 10⁹/L Newborn:8.0–24.0x10³/µL or 8.0–24.0x10⁹/L

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Overall function of leukocytes is in mediating immunity:

• Innate
• Adaptive

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Neutrophils in two forms:

Segmented
Band shape

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Major cytokine responsible for the stimulation:

Granulocyte Colony-Stimulating Factor (G-CSF)

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also known as colony-forming units granulocyte, erythrocyte, monocyte and megakaryocyte(CFU-GEMMs)

CMP

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consists of HSCs that are capable of self-renewal and differentiation.

Stem cell pool

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consists of cells that are dividing

Proliferation pool

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consists of cells undergoing nuclear maturation that form the marrow reserve and are available for release

Maturation pool

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(Maturation pool)

Releases:

metamyelocytes, band neutrophils, and segmented neutrophils

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Proliferation pool releases

Myeloblast
Promyelocytes
Myelocytes

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is characterized by:
• A high N:C ratio of 8:1 to 4:1;
• Slightly basophilic cytoplasm;
• Fine nuclear chromatin; and
• Two to four visible nucleoli.
• It has no visible granules when observed under light microscopy with Romanowsky stain.

Type 1 myeloblasts

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Shows the presence of dispersed primary (azurophilic) granules in the cytoplasm which does not exceed 20 per cell

Type II Myeloblast

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• Have a darker chromatin and a more purple cytoplasm
• Rare in normal bone marrows, but they can be seen in certain types of acute myeloidleukemias

Type III myeloblasts

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It has been proposed to combine Type II and Type III blasts into a single category of

granular blasts

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• Comprise 1% to 5% of the nucleated cells in the bonemarrow.
• Relatively larger than the myeloblast cells and measure16 to25 µmindiameter.

Promyelocyte

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• Nucleus: round to oval and is often eccentric.
• A paranuclear halo or “hof” is usually seen in normal promyelocytes but not in the malignant promyelocytes of acutepromyelocytic leukemia.
• Chromatin clumping may be visible, esp. around the edges of the nucleus.
• One to three nucleoli may be seen but may be obscured by thegranules

Promyelocyte

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• The cytoplasm is evenly basophilic and full of primary (azurophilic) granules. These granules are the first in a series of granules to be produced during neutrophil maturation

Promyelocyte

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• Make up 6% to 17% of the nucleated cells in the bone marrow
• Final stage to whichmitosis occurs
• Cell begins to manufacture secondary (specific) neutrophil granules.

Neutrophil myelocytes

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may look very similar to the promyelocytes in size and nuclear characteristics except that patches of grainy pale pink cytoplasm representing secondary granules begin to be evident in the area of the Golgi apparatus, referred to as “dawn of neutrophilia”. The granules eventually turn more lavender-pink than blue.

Early myelocytes

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measures 15– 18 µm, and the nucleus has considerably more heterochromatin. Nucleoli are difficult to see by light microscopy.

Late myelocytes

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• Consists of 3% to 20% of nucleated marrow cells. • The nucleus is indented (kidney bean shaped or peanut shaped), and the chromatin is increasingly clumped. • Synthesis of tertiary (gelatinase) granules may begin during this stage. • Cytoplasm contains very little residual RNA and therefore little or no basophilia

Neutrophil metamyelocytes

• Makes up 9% to 32% of nucleated marrow cells and 0% to 5% of the nucleated peripheral blood cells. • Evidence of basophilia is absent • Secretory granules, also known as secretory vesicles, may begin to be formed during this stage. • Nucleus is highly clumped and nuclear indentation that began in the metamyelocyte stage now exceeds one half the diameter of thenucleus.

Neutrophil band

• Make up 7% to 30% of nucleated cells in the bone marrow. • Secretory granules continue to be formed • The only morphologic difference between segmented neutrophils and bands is the presence of between two and five nuclear lobes connected by threadlike filaments. • Present in highest numbers among the leukocytes in adults.

Segmented neutrophils

• Formed during the promyelocyte stage • Last to be released through exocytosis

PRIMARY (AZUROPHILIC) GRANULES

• Formed during the myelocyte and metamyelocyte stage • Third to be released through exocytosis

SECONDARY (SPECIFIC) GRANULES

• Formed during metamyelocyte and band stages • Second to be released

TERTIARY GRANULES

• Formed during band and segmented neutrophil stages • First to be released (fuse toplasma membrane)

SECRETORY GRANULES (Secretory Vesicles)

Involves the movement of neutrophils and neutrophil precursors between the different pools in the bone marrow, the peripheral blood, and tissues.

Neutrophil kinetics

The transit time from myeloblast through myelocyte has been estimated to be roughly _____, and the transmit time through the maturation pool is approximately _____.

- 6 days - 4-6 days

Half-life of neutrophils:

approximately 7 hours

Onceinthe peripheral blood, neutrophils are divided randomly into a

CNP and MNP

_____ ______are of significant importance in allowing neutrophils to marginate as well as exit the blood and enter the tissues by the process known as ______

- Integrins and selectins - diapedesis

Major function of neutrophil

PHAGOCYTOSIS and DESTRUCTION of foreign material and microorganisms.

*Neutrophil* Steps of phagocytosis

1. Recognition and Attachment 2. Attachment and Engulfment 3. Killing and Digestion 4. Formation of Neutrophil Extracellular Traps (NETs)

The term has been used to describe the unique form of neutrophil cell death

NETosis

These cells are “acid loving” that causes them to appear brick red after staining with eosin.

Eosinophils

Eosinophils arise from

CMP

Eosinophilic promyelocytes can be identified cytochemically due to the presence of _______ in their primary granules.

Charcot-Leyden crystal protein

The first maturation phase that can be identified as eosinophilic using light microscopy and Romanowsky staining is the

Early myelocyte

Characterizedby the presence of large, pale, reddish-orange secondary granules, along with azure granules in blue cytoplasm.

Eosinophil myelocyte

Eosinophil Metamyelocytes and Bands Secondary granules increase in number, and a third type of granule is generated called

Secretory granule or secretory vesicle

Eosinophil Metamyelocytes and Bands Electron microscopy indicates the presence of two other organelles:

lipid bodies and small lysosomal granules

• Usually display a bilobed nucleus. • The cytoplasm contains characteristic refractile, orange-red secondary granules.

Mature eosinophils

Eosinophil primary granules

Charcot-leyden crystal protein

The time from the last myelocyte mitotic division to the emergence of mature eosinophils from the marrow is about

3.5 days

The mean turn over if eosinophils is approximately _____ cells/kg per day

2.2 x 10⁸

Eosinophil in the marrow:

9 and14 x10⁸ cells/kg

Once in the circulation, eosinophils have a circulating half-life of roughly ______ but it is prolonged wheneosinophilia occurs.

18 hours

Eosinophil survival time in human tissues ranges from

2-5 days

Ways of eosinophils to degranulate

- CLASSICAL EXOCYTOSIS - COMPOUND EXOCYTOSIS - PIECEMEAL DEGRANULATION

(Eosinophil degranulation) granules move to the plasma membrane, fuse with the membrane, and empty their contents into the extracellular space.

CLASSICAL EXOCYTOSIS

(Eosinophil degranulation) is a second mechanism in which granules fuse together within the eosinophil prior to fusing with the plasma membrane.

COMPOUND EXOCYTOSIS

Third method, in which secretory vesicles remove specific proteins from the secondary granules. These vesicles then migrate to the plasma membrane and fuse to empty the specific proteins into the extracellular space.

PIECEMEAL DEGRANULATION

Eosinophils also regulate mast cell function through the release of ______ that causes mast cell degranulation as well as cytokine production

major basic protein (MBP)

is a hallmark of allergic disorders

Eosinophilia

is capable of destroying tissue-invading helminths through the secretion of major basic protein and eosinophil cationic protein as well as the production of reactive species

Eosinophil

Are the least numerous WBCs that make up between 0% and 2% of circulating leukocytes and less than 1% of nucleated cells in the bone marrow.

Basophils

Lifespan of a mature basophil

60 hours

Functions as initiators of the allergic inflammation through the release of preformed cytokines.

Basophils

Also involved in helminth infections and also paly a nonredundant role in mediating acquired immunity against ticks.

Basophils

Mast cell progenitors (MCPs) originate from the

bone marrow and spleen

The major cytokine responsible for mast cell maturation and differentiation

KIT ligand (stem cell factor)

_____ is the major cytokine responsible for the growth and differentiation of monocytes.

Macrophage Colony Stimulating Factor (M-CSF)

Morphologic stages of monocyte development are

monoblasts, promonocytes, and monocytes

Monocytes are slightly immature cells whose ultimate goal is to enter the tissues and mature into

macrophages, osteoclasts, and dendritic cells

The nucleus may be round, oval, or kidney shaped, but more frequently is deeply indented (horseshoe shaped) or folded on itself.

Monocytes

Monocytes chromatin pattern is looser than other leukocytes and is sometimes described as

“lacelike or stringy”

Monocyte cytoplasm is blue-gray, with fine azure granules often referred to

azure dust or ground-glass appearance

• Liver – • Lungs – • Brain – • Skin – • Spleen – • Intestines –

–Kupffer cells –alveolar macrophages –microglia –Langerhans cells –Splenic Macrophages – intestinal macrophages

• Peritoneum – • Bone – • Synovial macrophages – • Kidneys – • Reproductive organ macrophages • Lymph node –

–peritoneal macrophages –osteoclasts –type A cell –renal macrophages • Reproductive organ macrophages –dendritic cells

Monocyte/Macrophage Functions

- Innate Immunity - Adaptive Immunity - Housekeeping functions

LYMPHOCYTES Divided into three major groups:

• T cells • B cells • Natural Killer (NK) Cells

play major role in the adaptive immunity

T cells and B cells

B and T cell development can be subdivided into:

Antigen-independent and Antigen-dependent phases

B lymphocytes develop initially in the bone marrow and go through three stages known as

pro-B, pre-B and immature B cells

Immature B cells, also known as

Hematogones

Effector B cells are antibody producing cells known as

- plasma cells (top) - plasmacytoid lymphocytes (bottom)

responsible for immunological memory

Memory cells

are produced much faster, are more prolonged, and are more effective than the events of the primary response

Secondary humoral responses

T cells are subdivided into major categories:

CYTOTOXIC (KILLER) T CELLS HELPER T CELLS REGULATORY T CELLS–

- are CD8+ and specialize in killing virus-infected, cancer, or foreign graft cells. Releases toxic chemicals called PERFORINS and GRANZYMES from its granules.

CYTOTOXIC (KILLER) T CELLS

also called CD4+ T cells; produce cytokines that promote differentiation of B cells into plasma cells, activate macrophages to become phagocytic, activate cytotoxic T cells, and induce many parts of inflammatory reaction

HELPER T CELLS

–areCD4+CD25+and play a crucial roles in allowing immune tolerance, maintaining unresponsiveness to self-antigens and suppressing excessive immuneresponse; produce peripheral tolerance which backs up the central tolerance emerging from the thymus

REGULATORY T CELLS

- cells mediate immune response against intracellular pathogens - cells mediate host defense against extracellular parasites, and also involved in induction of asthma and other allergic disease. - cells are involved in the immune responses against extracellular bacteria and fungi. - cells play a role in maintaining self-tolerance by regulating immune response.

• TH1 • TH2 • TH17 • Treg

are capable of killing target cells by secreting granules containing granzyme and perforin or by activating apoptotic pathways in the target cells

CD8+ effector lymphocytes

Also referred to as cytotoxic T lymphocytes.

CD8+ effector lymphocytes

are capable of killing certain tumor cells and virus-infected cells without prior sensitization

NK cells

Leukocyte Development, Kinetics, and Functions Flashcards

(91 cards)