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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 (CFUMeg), 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 WBC
5,000 10,000 per
mL
Neutrophils
40-75%
Lymphocyte
20-45%
s
Monocytes
2-6%
Eosinophils
1-4%
Basophils
0-1%
INFLAMMATION reaction of the BVs to
foreign cells
Causes accumulation of fluid and WBC in
extravascular tissue (aka edema)
Pus may or may not be present in
inflammation
Triggers the beginning of repair
(chemokines)
EVENTS AT SITES OF INFLAMMATIONS
Offending 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 phagocytosis
Signs of inflammation NOTE: signs =
symptoms!
o Signs = what doctor can observe
o 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 cell
accumulation
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 tissue
Activate endothelium >> bait the WBCs
WBC 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 captured
The 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
recruitment
much more efficient, it is not strictly required,
because high concentrations of chemoattractants 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
adhesion
absent E selectin >> less firmly adherent
leukocytes in response to local
chemoattractants or cytokine stimulation
Cytokines labeled Integrins: Neutrophils
1. CD-18- integrin important leukocyte
recruitment
o Absent CD-18- defective leukocyte adhesion
and T cell activation= leukocyte adhesion
o LAD Type 1 deficiency >> lethal
2. LFA 1- for firm leukocyte adhesion:
important neutrophil activation and
phagocytosis

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

PHAGOCYTOSIS
Steps involved in phagocytosis:
1. Chemotaxis and adherence of microbe to
phagocyte
2. Ingestion of microbe to phagocyte
3. Formation of a phagosome
4. Fusion of the phagosome with a lysosome
to form
a phagolysosome
5. Digestion of ingested microbe by enzymes

6. Formation of residual body containing


indigestible
material
7. 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 infection
If count >50,000 cells, assuming the cells are
normal-looking, leukemoid reaction.

Myelogenous leukemia: proliferation of


myeloid
cells 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

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

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 of
chemical: CHEMOTAXIS
Location
Macrophage
Bones
Osteoclast
Skin and
Histiocytes
subcutaneous
CT
Skin
Langerhans cells
Liver
Kupffer cells
Lungs
Dust cells/Alveolar
macrophages
Brain
Microglia
Kidneys
Mesangial cell/Kidney
macrophage
Placenta
Hofbauer cells (in the chorion
villi)
Spleen
Red pulp macrophages
Lymph nodes
Tissue 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 nodes
Generalized phagocytic system located in all
tissues, especially in those tissue areas where
large quantities of particles, toxins, and other
unwanted substances must be destroyed.

NEUTROPHILS

LYMPHOCYTES
MONOCYTES

EOSINOPHILS

Function
Phagocytosis
Formed in the
bone marrow,
function in the
tissues

Immature
macrophage in
the blood
Forms in the
bone marrow
and migrate to
tissue to be
called
macrophage
Allergic
Reactions
Parasitic
infection. Can
help
neutrophil
phagocytose
parasites.

BASOPHILS

Allergic
reactions
Response to
certain antigens
and
inflammation
along with mast
cells

Circulate in the
blood for 10-24
hours
Migrate into
tissues for 1-2 days

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, IL5, GM-CSF
few hours-few days

Purple-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 Elastase

Contain 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 sothatneutrophilscandotheirjobbetter.IL-1, IL-2, IL4, IL-5
Interferon- 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.

No visible granules
Pale blue cytoplasm

Enters tissue (macrophage) and swell 5 times in size


Monocytes are the mobile macrophages that circulate
in the blood
Become part of the monocyte-macrophage cell system
After monocytes enter tissues and become
macrophages, they attach to tissues and remains attached for
months or years until they are called via chemotaxis and become
mobile macrophages again

Red-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)

Has azurophilic and specific


granules

Main source of cytokine: IL-4


Percentage in blood: 0-0.7%
Basophils are similar to mast cells
Both Basophils & Mast cells liberate heparin in the blood that
prevent blood coagulation
Both Basophils & Mast cells release histamine as well
as smaller quantities of bradykinin & serotonin.
Heparin (anti-coagulant) and histamine (vasodilator) -> increase
blood flow to site of infection to facilitate
transport of more leukocytes
Heparin & histamine: source of IL-4 which stimulates
B lymphocytes which produce IgE to attract more
leukocytes

When attached to IgE,


basophils rupture and
release large quantities of
histamine and heparin,
bradykinin, serotonin and
slow-reacting substances of
anaphylaxis and lysosomal
enzymes