Maturation Process of All Cell Lines Flashcards
Leukocyte Life Cycle
Differentiate, proliferate, mature in BM (Except T lymphocytes - Thymus)
Develop from the pluripotential HSC
Growth factor stimulation
Stem cell proliferates and differentiates
Various types of leukocytes develop
Mature Leukocyte Life Cycle
Are stored in the BM, or Released in the peripheral blood Circulate briefly Move into the tissues when stimulated Perform function of host defense primarily in the tissues
Leukocyte Normal Ranges
Newborn: WBC count is high, 9-30 x 103/μL
Left-shifted (immature) granulocytes cells are found in circulation
Childhood: Gradually decreases through childhood, 4.5-18 x 103/μL
Adult: 4.5-11 x 103/μL
Neutrophil Life Cycle
Lifespan spent in 3 areas
BM – development and storage
Peripheral blood – circulate for a few hours
Tissues – perform their function of host defense
Neutrophil Normal Ranges
Children: 1.5-8.5 x 103/ul, relative 35-45%
Adult: 1.8-7 x 103/ul, relative 40-80%
Neutrophil Maturation Stages
Myeloblast Promyelocyte Myelocyte Metamyelocyte Band neutrophil Segmented neutrophil
Neutrophil Maturation Characteristics- Nucleus
Entire size of cell slightly decreases Nucleus Chromatin condenses N:C ratio decreases Nucleoli disappear Nucleus indents and segments
Neutrophil Maturation Characteristics- Cytoplasm
Loses basophilia, becomes neutral/pink
Production of purple/dark primary granules
Lose visibility as cell matures
Production of secondary granules
Increasingly occurs in the later stages of maturation
Give neutrophils their characteristic pink color
Myeloblast Characteristics
Nucleus: High N:C ratio, Usually round or oval, Lacy/evenly stained chromatin pattern, Nucleoli are usually visible
Cytoplasm: Small amount of basophilic agranular cytoplasm, Sometime shows light area adjacent to the nucleus, Golgi apparatus
Promyelocyte Characteristics
Nucleus: High N:C ratio, Chromatin pattern still fine, But more coarse than a blast, Nucleoli are usually visible
Cytoplasm: Basophilic, Prominent purple primary granules
Myelocyte Characteristics
Nucleus: Round or oval, Decreasing N:C ratio, Fairly condensed chromatin pattern, Nucleoli usually not visible, Last stage capable of mitosis
Cytoplasm: Variable
Early myelocyte: Basophilic cytoplasm, Scattered primary granules
Later myelocyte: Neutral to pink cytoplasm, Few primary granules, Becomes pink as secondary granules are produced
Metamyelocyte Characteristics
Nucleus: Coarse and clumped chromatin, No nucleoli, Nuclear indentation begins, Kidney bean shape, Indentation cannot exceed half the width of a theoretically round/oval nucleus
Cytoplasm: Neutral pink color, May retain slight basophilic tinge, Due to predominance of secondary granules, Primary granules lose visibility, With an infection, Primary granules may be seen, Known as toxic granulation
Nuclear Indentation Criteria
Myelocyte: The nucleus is round, oval, or slightly flattened on one side.
Metamyelocyte: The nucleus is beginning to indent but does not exceed the half-way point of a theoretical round nucleus
Band: The nucleus is indented beyond the half-way point of a theoretical round nucleus
Band Neutrophil Characteristics
Nucleus: Coarse and clumped chromatin, No nucleoli, Indentation exceeds half the diameter of the theoretically round/oval nucleus
Cytoplasm: Neutral pink color, Due to predominance of secondary granules, Primary granules lose visibility, With an infection, Primary granules may be seen, Known as toxic granulation
Segmented Neutrophil Characteristics
Nucleus: Coarse and clumped chromatin, No nucleoli, 3-5 segments connected by a thin nuclear filament, Barr body sometimes visible (Females only- An expression of inactive X chromosome)
Cytoplasm: Neutral pink color, Due to predominance of secondary granules, Primary granules lose visibility
-With an infection, Primary granules may be seen, Known as toxic granulation
Neutrophil Granules- Primary
Also known as: Azurophilic granules, Non-specific granules; Dark, purple, Prominent, Lose the ability to stain with maturation
Exception: toxic granulation
Contents: Cytotoxic compounds, Myeloperoxidase (MPO), Encased by phospholipid membrane
Neutrophil Granules- Secondary
Also known as: Specific granules
Small, sand-like, Gives cytoplasm a characteristic pink/neutral color
Contents: Peroxidase negative, Pro-inflammatory and chemotactic factors, Encased by a phospholipid membrane
Neutrophil Function
Part of the innate immune system (Does not require activation)
One of the first responders to inflammation
Phagocytosis and destruction of bacteria
Release of chemotactic factors
Neutrophil Activity
Circulate: ½ neutrophils circulate freely
OR
Marginate: ½ neutrophils slowly roll on the endothelial surface
Upon stimulation- Move to site, kill invading cell or bacteria
4 steps
Adherence
Migration
Phagocytosis
Bacterial killing
Neutrophil Invasation
Adherence: Activated by inflammatory cytokines, Neutrophils interact with vascular endothelial cell
Arrest: Neutrophils are bound more tightly to endothelium
Diapedesis: Squeezes through endothelial cells into tissues
Migration: Once in the tissues, Neutrophils migrate by following cytokines, Known as chemotaxis, Crawling motion to infected site
Neutrophil Phagocytosis
Recognition of pathogen: Enhanced by opsonized organisms
Pseudopods: Surround and internalize the organism
Phagosome: Fusion of granules/lysosomes with the ingested object, Formation of phagolysosome, Organism is killed and digested
Respiratory Burst
Requires large amounts of energy
Oxygen-dependent- Generates larges amounts of cytotoxic reactive oxygen species (ROS), Rapid release of ROS into phagolysosome, Oxidation, disruption, and death of microorganism
Production of ROS is catalyzed by MPO- MPO is contained in primary granules, Catalyzes a reaction during the respiratory burst to produce hypochlorous acid
Eosinophil Maturation
Same 6 stages as neutrophil maturation Myeloblast Promyelocyte Eosinophilic myelocyte (First recognizable stage) Eosinophilic metamyelocyte Eosinophilic band Segmented eosinophil
Mature Eosinophil Characteristics
Nucleus: 2-3 lobes
Cytoplasm:,Filled with large eosinophilic granules, Red-orange, Larger than neutrophil granules, Uniform size, evenly distributed, Contains proinflammatory cytokines
Eosinophil Function
Degranulation: Allergies, Parasitic worms
Capable of phagocytosis
Basophil Maturation
Same 6 stages as neutrophil maturation Myeloblast Promyelocyte Basophilic myelocyte Basophilic metamyelocyte Basophilic band Segmented basophil
Mature Basophil Characteristics
Segmented nucleus, Large purple-black granules, Unevenly distributed throughout the cytoplasm (May obscure the view of the cytoplasm and nucleus)
Contains: Histamine (Vasodilation, Increases vascular permeability), Tryptase (An inflammatory enzyme), Heparin (An anticoagulant)
Basophil Function
Known as a mast cell when in the tissues
IgE-mediated allergies
IgE binds to mast cells
Degranulation occurs when IgE binds antigen- Causes immediate hypersensitivity reactions: Allergic rhinitis, Asthma, Urticaria (hives), Anaphylaxis
Monocyte Characteristics
Produced in BM
Closely related to the granulocytes (Several similar functions)
More specialized functions
Bipotential progenitor cell (CFU-GM)
Monocyte Maturation
3 stages of monocyte maturation
Monoblast: Monoblasts cannot be microscopically differentiated from other blasts (In practice, we DO NOT microscopically differentiate blasts), The characteristics are generally the same (Just call it a blast)
Promonocyte: A mix between a blast and a mature monocyte, Fine chromatin pattern, visible nucleoli
Monocyte Physical Characteristics
Largest mature cell in circulation
Nucleus: Variable shapes, Commonly horseshoe or bean shaped, Loose chromatin pattern
Cytoplasm: Blue-gray cytoplasm, Commonly vacuolated, Very fine sand-like granules, Small amounts of peroxidase
Macrophage Characteristics
Also known as Histiocytes
The tissue form of monocytes- Monocyte enters tissues, Matures into macrophage, Lives for months
Description: Becomes progressive larger
Nucleus: Round appearance, Nucleoli appear
Cytoplasm: Blue-gray with ragged edges, Many vacuoles, May see ingested material
Macrophage Function
Innate immunity
Phagocytic scavengers: Cellular debris, Denatured proteins, Aged RBCs, recycle iron
Acquired immunity
A professional antigen presenting cell (P-APC): Innate phagocytosis of infectious agent, Presents antigen via MHC Class II to T-helper cells, Production of cytokines, Stimulate hematopoiesis, Chemotactic factors for more immune cells
Professional APCs
Macrophages
B-cells
Dendritic cells
While in the tissues: Ingest and process antigens, Migrate to secondary lymphoid tissues, Present antigens to T-helper (Th) cells via MHC Class II
Non-professional APCs
Most nucleated cells through the body
When virally infected or cancerous- Process and present viral/cancer antigens to cytotoxic T (Tc) cells via MHC Class I, Apoptosis is induced by Tc cells, Cancer/virus is eliminated
Lymphocyte Life Cycle
Continuously move in and out of lymphoid tissues and circulation
95% of all lymphs are in lymph nodes and spleen
Long lifespan: 80% of lymphs have life span from months to years, Most other leukocytes only live a few days, Develop into memory cells, Proliferate upon re-activation
Lymphocyte Types
All originate in the BM Identical, but functionally different T cells B cells Natural killer (NK) cells
T and B lymphopoiesis
Antigen-independent lymphopoiesis: Takes place in primary lymphoid tissue
B cells: Remain in the BM
T cells: Quickly move to the thymus
T and B cells: Become immunocompetent, Do not interact with antigens, Are considered naive, Exit primary lymphoid tissues, Migrate to secondary lymphoid tissue
Antigen-dependent lymphopoiesis
Takes place in secondary lymphoid tissues- Spleen, Lymph nodes
Professional APCs present antigens
Recognition of and interaction with antigens
T and B cells proliferate
Perform their unique role, or become memory cells
Mediate the acquired immune response
T Cells
Function: cell-mediated immunity
Tc cells: Recognize antigen presented via MHC Class I, Induce presenting cell to undergo apoptosis
Th cells: Recognize antigen presented via MHC Class II, Proliferate and quickly activate the acquired immune system, Stimulate B-cells to become antibody-producing plasma cells, Enhance the function of phagocytes, Produce cytokines, Orchestrates immune response, Activation and recruitment of more immune cells
B cells
Professional APCs, Humoral immunity (Activated B cells become plasma cells, Produce antigen-specific antibodies, Neutralizes or opsonizes the antigen)
NK Cells
Same function as Tc cells but with important differences
Does not require antigen/MHC presentation to become activated
Major component of the innate immune system
Lymphocyte Maturation
3 stages of maturation
Lymphoblast: Lymphoblasts cannot be microscopically differentiated from other blasts (We DO NOT microscopically differentiate blasts)
Prolymphocyte: Look like a regular small lymphocyte, Prominent nucleolus
Lymphocyte: Highly variable
Large Lymphocyte
Up to twice the size of a RBC
Nucleus: Lower N:C ratio, Chromatin can be more dispersed, May see nucleolus
Cytoplasm: Lighter blue, Azurophilic granules may be present
Reactive Lymphocytes
Also known as: Variant lymphocytes, Atypical lymphocytes
Nucleus: Lower N:C ratio, Variable shapes, Chromatin more dispersed, May see nucleoli
Cytoplasm: Azurophilic granules, Sometimes small vacuoles, May show indentation by surrounding RBCs, Darkened cytoplasmic borders
Few may be seen in healthy individuals
Increased reactive lymphs often indicates viral infection
Plasma Cells
The terminally differentiated form of B-cells, Antibody-producing cells, Round or oval shape
Nucleus: Eccentric placement, Nucleoli are not present
Cytoplasm: Golgi apparatus is apparent, Clearing near the nucleus, Deeply basophilic rim, May have azurophilic granules
