Occupies the buffy coat portion of a centrifuged blood sample (along with platelets). Main function: defense

Pluripotent stem cell becomes progenitor cells (Colony-Forming Unit-Megakaryocytes (CFU- Meg), Colony-Forming Unit-Granulocytes, Monocytes (CFU-GM)) based on the right factors (Cytokines/interleukins).

Normal values for WBC count -cytosis = above normal (leukocytosis); while - penia = below normal (leukopenia)Total WBC5,000 10,000 per mL

Neutrophils40-75%

Lymphocytes20-45%

Monocytes2-6%

Eosinophils1-4%

Basophils0-1%

INFLAMMATION reaction of the BVs to foreign cells Causes accumulation of fluid and WBC inextravascular tissue (aka edema) Pus may or may not be present in inflammation Triggers the beginning of repair (chemokines)EVENTS AT SITES OF INFLAMMATIONSOffending organism enters tissue that produces cytokines (CHEMOTAXIS) Vasodilation blood vessel circumference increases thus more blood flows through blood vessel Increased permeability of capillaries so WBCs can move from vessel to extravascular tissue Destruction of pathogens by phagocytosisSigns of inflammation NOTE: signs = symptoms!o Signs = what doctor can observeo Symptoms = what the patient feels Rubor/redness due to blood vessel dilation Calor/heat due to blood vessel dilation Tumor/swelling from extra fluid and cellaccumulation Dolor/pain nerves impinged by the swollen part

STEPS OF INFLAMMATION

1. Capture - WBC in vessel is initially flowing in the middle of the vessel, and not close to endothelium. Chemoattractants >> Come from the tissueActivate endothelium >> bait the WBCsWBC sticks to attractants on endothelium P-selectin on endothelial cell attaches to: PSGL1(p selectin glycoprotein ligand 1) on WBC(neutrophil/eosinophil/monocytes) Initial change of velocity

2. Rolling - Further change of velocity (slowing down) once the WBC is capturedThe more sticking, the higher the attachments.

3. Slow rolling P selectin: triggers slowing down Activated by surface-bound chemoattractants and through adhesion molecule-based signaling Although slow rolling makes leukocyte recruitmentmuch more efficient, it is not strictly required, because high concentrations of chemo-attractants can also arrest fast-rolling leukocytes Slow-rolling leukocytes do not stop abruptly, but show a gradual decrease of their rolling velocity before becoming adherent.4. Firm adhesion E-selectins - role in converting to firm adhesionabsent E selectin >> less firmly adherent leukocytes in response to local chemoattractants or cytokine stimulationCytokines labeled Integrins: Neutrophils 1. CD-18- integrin important leukocyte recruitment o Absent CD-18- defective leukocyte adhesion and T cell activation= leukocyte adhesiono LAD Type 1 deficiency >> lethal2. LFA 1- for firm leukocyte adhesion: important neutrophil activation and phagocytosis

5. TransmigrationEndothelial activation - increased transcription and protein synthesis >> increased expression of adhesion molecules in response to locally produced cytokines and inflammatory mediators from site of injuryIL-8 (interleukin 8) - stimulates transmigrationRoles of ICAM-1; cadherin, CD11/18; VLA-4 for transmigrationVLA-4 (4 integrin) = binds endothelium for transmigration

PHAGOCYTOSISSteps involved in phagocytosis:1. Chemotaxis and adherence of microbe to phagocyte2. Ingestion of microbe to phagocyte3. Formation of a phagosome4. Fusion of the phagosome with a lysosome to forma phagolysosome5. Digestion of ingested microbe by enzymes6. Formation of residual body containing indigestiblematerial7. Discharge of waste materials

Bactericidial agents released by phagocytes superoxide; hydroxyl radicals toxic nitrogen free radicals (nitric oxide) antimicrobials - defensins enzymes = lysozyme, acid hydrolases

E. CLINICAL CORRELATIONS Neutrophilia (neutrophil predominance)Neutrophil count >75% (10,000 cells)Indicates bacterial infectionIf count >50,000 cells, assuming the cells are normal-looking, leukemoid reaction.

Leukopenia Bone marrow produces very few WBCs, leaving the body vulnerable to foreign pathogens and opportunistic organisms. Causes: too much irradiation, exposure to chemicals/ drugs containing benzene or anthracene nuclei Symptoms: ulcers in the mouth and colon Treatments: antibiotics to ward off infection, bone marrow transplants

Leukemia Uncontrolled production of WBC Lymphocytic leukemia: usually beginning in a lymph node, and subsequent migration of malignant lymphoid cells Myelogenous leukemia: proliferation of myeloidcells in the bone marrow. Cells may have undergone different levels of differentiation; undifferentiated cells produce acute conditions, while more differentiated cells produce chronic conditions.

Effects: metastasis to the spleen, lymph nodes, liver and other vascularized regions; development of infection; severe anemia; bleeding (caused by lack of platelets), metabolic starvation

Macrophages - Mature monocytes in tissues Much more powerful phagocytes than neutrophils After digesting particles, macrophages can extrude/spit residual products and often survive and functions for many more months Exits the blood vessel via diapedesis and move through the tissues via ameboid movement Many different chemical substances in the tissues cause macrophages to move toward the source ofchemical: CHEMOTAXISLocationMacrophage

BonesOsteoclast

Skin and subcutaneous CTHistiocytes

SkinLangerhans cells

LiverKupffer cells

LungsDust cells/Alveolar macrophages

BrainMicroglia

KidneysMesangial cell/Kidney macrophage

PlacentaHofbauer cells (in the chorion villi)

SpleenRed pulp macrophages

Lymph nodesTissue macrophages

Monocyte-Macrophage Cell System (Reticuloendothelial System) o The total combination of monocytes, mobile macrophages, fixed tissue macrophages, and a few specialized endothelial cells in the bone marrow, spleen and lymph nodesGeneralized phagocytic system located in all tissues, especially in those tissue areas where large quantities of particles, toxins, and other unwanted substances must be destroyed.

Function

NEUTROPHILSPhagocytosisFormed in the bone marrow, function in the tissues

Circulate in the blood for 10-24 hours Migrate into tissues for 1-2 daysPurple-stained cells (using Wright stain)

Granules contain enzymes that degrade microbes (know these!) Antimicrobial peptides (AMPs) Alpha defensins Azurocidin Cathepsins Lactoferrin Lysozyme Proteinase-3 Gelatinase Collagenase ElastaseContain adhesion molecules, to attach and move out of the endothelium (movement called diapedesis)Factors within the tissues produced by other phagocytic cells, to delay apoptosis so that neutrophils can do their job better.IL-1, IL-2, IL-4, IL-5Interferon- G-CSF, GM-CSF, LPS Cleared by macrophages and dendritic cells found within the tissue Removed by liver, spleen and bone marrow. There is always a turnover (rate of replacement) of neutrophils at any given time.Formation enhanced by IL-1, IL-3, IL-6. Lifespan enhanced by IL-5 and IL-3.

LYMPHOCYTES

MONOCYTESImmature macrophage in the bloodForms in the bone marrow and migrate to tissue to be called macrophageNo visible granulesPale blue cytoplasmEnters tissue (macrophage) and swell 5 times in size Monocytes are the mobile macrophages that circulatein the blood Become part of the monocyte-macrophage cell system After monocytes enter tissues and becomemacrophages, they attach to tissues and remains attached for months or years until they are called via chemotaxis and become mobile macrophages again

EOSINOPHILSAllergicReactions

Parasitic infection. Can helpneutrophil phagocytose parasites.Life cycle Matures in 5-6 days Circulate in blood 8-12 hours Migrate to tissues then remain for up to 4 days Respond to cytokines: IL-3, IL-5, GM-CSFRed-staining(acidophilic)Granules: Histamine exposure to allergens causes degranulation, causes rashes in the body. Peroxidase Ribonuclease Lipases Plasminogen Major basic protein (MBP) binds with parasite proteins for phagocytosis Eosinophil cationic protein (ECP) Eosinophil derived neurotoxin (EDN)

BASOPHILSAllergic reactionsResponse to certain antigens and inflammation along with mast cells

few hours-few daysHas azurophilic and specific granules

When attached to IgE, basophils rupture and release large quantities of histamine and heparin, bradykinin, serotonin and slow-reacting substances of anaphylaxis and lysosomal enzymesMain source of cytokine: IL-4Percentage in blood: 0-0.7%Basophils are similar to mast cellsBoth Basophils & Mast cells liberate heparin in the blood that prevent blood coagulationBoth Basophils & Mast cells release histamine as wellas smaller quantities of bradykinin & serotonin. Heparin (anti-coagulant) and histamine (vasodilator) -> increase blood flow to site of infection to facilitatetransport of more leukocytes Heparin & histamine: source of IL-4 which stimulatesB lymphocytes which produce IgE to attract moreleukocytes