Leukocytes and Their Functions

Leukocytes l

• Leukocytes are also known as white blood cells
• They are derived from being colorless compared to red blood cells
• They are the main component of the buffy coat, which appears white in color
• There are at least 10 different types of leukocytes

Function

• Their major function is a defense mechanism
• They are part of the innate (non-specific) immune system
• They can activate the complement system
• Their major function is phagocytosis and destruction of foreign materials and microorganisms
• This process involves seeking (chemotaxis, motility, and diapedesis) and destruction (phagocytosis, digestion)

Leukocyte Staining

• Granulocytes are a group of leukocytes with cytoplasmic granules and lobulated or segmented nuclei
• Eosinophils are acidic granules that stain with acid stains (eosin)
• Basophils have acidic granules that stain with basic stains (methylene blue)
• Neutrophils have granules that react with both acidic and basic stains, resulting in a pink to lavender color

Mononuclear cells/Agranulocytes

• Mononuclear cells/agranulocytes have round, oval, indented, or folded nuclei

Leukocyte Population

• Factors influencing leukocyte population include sex, age, activity, time of day, and ethnicity
• White blood cells (WBCs) react to stress, being consumed, or being destroyed
• There needs to be enough production

Granulocytes

• Granulocytes are a group of leukocytes characterized by their granules, which are cytoplasmic
• They have lobulated or segmented nuclei

Neutrophils

• Neutrophils contain nonspecific granules
• Red blood cells (RBCs) are shown in the image for comparison

Kinetics

• Once in the blood, neutrophils are divided into circulating neutrophil pool (CNP) and marginated neutrophil pool (MNP)
• MNP neutrophils are loosely localized to the walls of capillaries in tissues such as the liver, spleen, and lungs
• MNP and CNP neutrophils are roughly equal in number and exhibit no difference in function
• Neutrophils in the blood have a half-life of 7 hours
• MNP can enter tissues through diapedesis, while those that don't migrate will undergo apoptosis and be removed by splenic macrophages, which is dependent on whether they respond to infection or inflammation
• In response to infection or inflammation, the neutrophils have a longer lifespan, otherwise, they have varying half-lives measured in hours

Eosinophils

• Eosinophils have a circulating half-life in the blood of roughly 18 hours
• Their tissue destination is the underlying, epithelial surfaces in the respiratory, gastrointestinal, and genitourinary tracts
• In tissues their life span can range from 2 to 5 days
• They have multiple functions, including compound exocytosis, piecemeal degranulation, acting as antigen-presenting cells (APCs), and inducing Type 1 or 2 immune responses
• Eosinophils regulate mast cell formation through the release of major basic protein (MBP)
• They destroy tissue-invading helminthes and prevent reinfection
• They're associated with asthma, and inflammation of the airways

Basophils

• Basophil kinetics is difficult to understand due to their low numbers
• A mature basophil has an estimated lifespan of 60 hours, governed by anti-apoptotic pathways
• They've been historically categorized as less important than mast cells in allergic reactions, but they share some similarities, including IgE receptors, and they do contain histamine in their secondary granules
• Basophils participate in controlling helminth infections in conjunction with eosinophils

Mast Cells

• Mast cells are not leukocytes but tissue effector cells in allergic and inflammatory responses
• They share phenotypic and functional similarities with basophils and eosinophils
• They develop in peripheral blood and tissues
• Mast cells have anti-inflammatory and immunosuppressive functions

Agranulocytes/Mononuclear Cells

• These cells include white blood cells (WBCs) with no visible granules and single or multiple nuclei
• Examples include lymphocytes, monocytes and macrophages

Monocytes/Macrophages

• Promonocytes may experience two mitotic divisions within 60 hours to produce approximately 4 monocytes
• When there's a high demand, 16 monocytes can form within 60 hours.
• Monocytes circulate for roughly 3 days before entering tissues and differentiating into macrophages.
• Their size reaches between 40 and 50 micrometers in diameter
• The lifespan of macrophages varies based on whether they're responding to inflammation or infection, or are acting as "resident" macrophages, such as Kupffer cells or alveolar macrophages, which may live longer in their tissues
• Monocytes/Macrophages functions include innate immunity, adaptive immunity, and housekeeping functions

Innate Immunity

• Monocytes/Macrophages recognize many bacterial pathogens, stimulating an inflammatory response, releasing cytokines, and phagocytosing items
• They produce nitric oxide, which is cytotoxic to viruses, bacteria, fungi, protozoa, helminths, and tumor cells
• They possess Fc receptors to phagocytosing foreign materials coated with antibodies (Abc) or complement

Adaptive Immunity

• Both macrophages and dendritic cells are responsible for presenting antigens and fragments (APCs) for activating T and B lymphocytes that initiate adaptive immune responses, where dendritic cells are most efficient
• They are capable of degrading antigens for immune response activation

Housekeeping Functions

• Monocytes/Macrophages remove dead cells, debris, and dead cells from areas of infection and tissue damage
• They destroy senescent red blood cells (RBCs)
• They synthesize and maintain a variety of proteins, including coagulation factors, complement components, cytokines, growth factors, and enzymes

Lymphocytes

• Lymphocytes are divided into three major groups: T cells, B cells, and NK cells
• T and B cells are key players in adaptive immunity, while NK cells are part of innate immunity
• Lymphocytes are not end cells, but resting cells that can multiply into memory and effector cells to respond to stimulation
• They recirculate between the bloodstream and tissues
• B and T cells can modify antigen receptor segments to create a variety of antibodies and surface receptors
• T and NK cells develop and mature outside the bone marrow (BM)
• Lymphocyte functions and kinetics are part of immunology

WBC Anomalies and Leukemia

• Morphological abnormalities in WBCs can indicate conditions like leukemia.

Morphological Abnormalities

• Normal morphology examples of various white blood cell types (WBCs): Lymphocyte, Monocyte, Basophil, Eosinophil, Neutrophil are shown with diagrams and micrographs
• Pelger-Huet Anomaly: neutrophils with hypolobulated, rounded nuclei, condensed chromatin; thin chromatin strands may connect the lobes to make a pinch-nez (spectacle) or, a wider bridge gives the appearance of a peanut
• Hyper-segmented Neutrophil: neutrophils with more or higher number of nuclear lobes that are abnormal
• Drumsticks: inactive X chromosome in females

Alder-Reilly Anomaly

• Recessive disease.
• Cytoplasmic deposition of mucopolysaccharides (lipids)
• Appears as metachromatic granules

Chediak-Higashi Syndrome

• Rare autosomal recessive trait
• Abnormally large, peroxidase-positive lysosomes are seen in neutrophils and other cells
• Result in albinism

May-Hegglin Anomaly

• Rare autosomal dominant condition
• Presence of large Dohle-body-like formations (combination of rods and granules that are ribosomally derived).

Dohle Bodies

• Small blue-gray inclusions in neutrophil cytoplasm, often at the margins
• Composed of rough endoplasmic reticulum and glycogen granules
• Associated with inflammatory disorders and burns

Toxic Granulation

• Larger, more basophilic granules than normal are present in neutrophils
• Common in severe bacterial infections, burns, malignancies, and drug reactions.

Reed-Sternberg Cells

• Large cells with multi-lobed, characteristic "mirror-like" nuclei
• Seen in Hodgkin's lymphoma

Hand-mirror cells

• T cell characteristic with a 'hand-mirror' shape within T-cell acute lymphocytic leukemia

Sezary Cells

• Lymphocytes with convoluted/folded nuclei
• Seen in advanced mycosis fungoides

Smudge Cells

• Fragile lymphocytes rupturing during preparation
• Nuclei spread out, with hazy borders

Atypical Lymphocytes

• Large lymphocytes with foamy or vacuolated cytoplasm
• Irregular nuclei; commonly seen in viral infections like Herpes and HIV
• Basophilic cytoplasm and coarse chromatin

Activated Monocytes

• Associated with inflammatory reactions, like bacteremia
• Increased granulation

Auer Rods

• Red, needle-like structures of primary granules
• Characteristic of acute myeloid leukemia (AML)