Hem 4 - Leukocytes Flashcards
what are the two major classes of WBC broken into
granulocyte, mononuclear cells
where do WBC go after they leave the bloodsteam
WBC are transported to sites of infection/injury where
they leave the bloodstream and perform immune and
defense functions against pathogens and tissue damage
lifespan of WBC and how often they need to be replenished
Although numbers are much lower than RBC (1/1000th as
many), they have a much shorter lifespan in circulation and
need to be continuously replenished.
what do changes in WBC numbers, type and morphology reflect
Changes in WBC numbers, morphology and cell types within
blood reflect systemic changes (eg. infection) - the distribution
of the various WBC types often reflects the nature and
severity of those stressors (bacterial, viral, parasitic)
evaluation of the leukon - what to look at to count and characterize cells in blood
Count and Characterize the cells in blood (normally done
as part of the CBC):
* Total WBC count (per μl or ml of blood)
* Differential WBC count (% of WBC of each type)
* Blood smear (morphology of WBCs)
what is:
Leukocytosis, Leukopenia, and Pathological vs Physiological
Leukocytosis: Increase in the total number of WBCs.
Leukopenia: Decrease in the total number of WBCs.
In either case the task is then to determine whether the
change is:
* Pathological: Processes such as infection, inflammation
tissue damage, cancer or other underlying disease alter
WBC numbers and distribution.
* Physiological: Hormones such as cortisol, epinepherine
can also alter WBC numbers and distribution.
To make these determinations, we first need to understand
the biology of the different cell types.
circulating WBC - branches and types within the branches
granulocytes, agranulocytes
granulocytes = neutrophils (65-75%), eosinophils (2-5%), basophils
agranulocytes = lymphocytes (20-25%), monocytes (3-8%)
Neutrophils - what type of cells are these, what do they do, circulation pattern, what are the granules responsible for and their names
Major phagocytic cells in the innate immune response
- “First responders” at sites of infection, tissue damage.
- Continually circulating- binding and releasing from
vascular endothelia - Granules in the cytoplasm responsible for killing
microbes - Primary granules
- Secondary granules
intramedullary phase: neutrophols and their precursors in bone marrow (pools and what is in this)
pool 1 = proliferative/mitotic pool = myeloblasts, promyelocytes, myelocytes
pool 2 = maturation pool = metamyelanocytes, band cells
pool 3 = storage or reservation pool = band cells, mature neutrophils
intravascular phase: neutrophils in circulation (pools and what is happening with them, normal lifespan, what affects the lifespan)
circulating pool = neutrophils in circulation
marginal pool = neutrophils marginated along capillary
Normal neutrophil lifespan in the bloodstream (both pools) is
less than 24 hours.
* This can be dramatically decreased by infection etc. when the
transit time becomes much shorter.
tissue phase: neutrophils leave circulation and enter tissue
Normally neutrophils enter the tissues by diapedesis
through the intercellular junctions of vascular endothelium.
- Stimulated by chemotactic factors secreted by bacteria,
other WBC, damaged cells in tissue. - This is a one-way process – once in tissues, neutrophils
perform their functions and ultimately die after 24 – 48 h. - Neutrophil migration to the tissues depends on severity
and duration of tissue injury. - Neutrophil influx into tissue is maintained by new cells
entering blood from bone marrow.
what is the order of events for a neutrophil to go from ciruculation to do its job in tissue
pavementing, emigration, chemotaxis , phagocytosis
will you ever see recirculation of neutrophils that have emirgrated
never, it is a one way street
examples of what happens when neutrophils accumulate in large numbers at tissue sites
pyothorax, pyometra
steps in neutrophil responses to pathogens (phagocytosis)
- Bacterium becomes attached
to membrane evaginations
called psueudopodia - Bacterium ingested in the
phagosome - Phagosome fuses with
lysosome - Lysosomal enzymes
digest captured material - Digestion products are
released from the cells
immaure neutrophils in circulation: band cells/band neutrophils – what do they look like, what is an increased amount called and what does it indicate, what other conditions can cause it
Band cells or band neutrophils have
unsegmented nuclei and is the stage immediately preceding the mature neutrophils
An increased proportion of bands in the peripheral blood is often referred to as a ‘left shift’, and may indicate the presence of infection.
Other conditions, such as hypoxia
and shock, can also cause a left shift
changes in blood neutrophil counts can be caused by changes in one or more of the following what?
- The rate of neutrophil production (granulopoiesis)
- The extent of neutrophil influx from the marrow pool to the
blood - A shift of neutrophils between the circulating and marginal
pools - The intravascular life span of neutrophils
- The rate of efflux from the blood to tissue
what are the responses to infection and inflammation and what happens during them?
Initial Response: Decrease in circulating neutrophil numbers due to increase margination and migration into the tissues
Intermediate Phase: Neutrophils from the marrow reserve are released into the vasculature causing an increase in neutrophil numbers
Progressive Phase: As the inflammation progresses, both marginal and circulating pools increase due to increased granulopoiesis and release of newly formed cells into the vasculature.
neutropenia - what is it characterized by, what is the classification of it, what % do they make up
Characterized by an abnormally low number of neutrophils
- Neutrophils usually make up 50-70% of circulating white
blood cells and serve as the primary defence against infections by destroying bacteria in the blood - Neutropenia can be acute or chronic depending on the duration of the illness
what causes a decrease in neutrophil numbers?
Increased efflux to tissues (early phases of infection)
- Decreased granulopoiesis or release from the marrow
(leukemia, myelofibrosis, chemotherapy) - Decreased cell survival in vascular compartment
are there differences in appearance of neutrophils in species
yes
toxic changes in neutrophils - what happens with development, term for the change, what are toxic changes, what do they look like
When neutrophils develop and mature at an accelerated rate in
the presence of significant infection or tissue damage, their
appearance is altered by the presence of TOXIC CHANGES.
- These are morphologic abnormalities acquired during
maturation under conditions that intensely stimulate neutrophil
production and shorten the maturation time in marrow. - Most of the toxic changes reflect accelerated granulopoiesis
and release from the marrow – incomplete chromatin
condensation and ribosomal proteins remaining in cytoplasm (in
many ways analogous to reticulocytes when RBC maturation
and release is accelerated in response to anemia). - Usually (but not always) the changes are observed in band
cells, as these are quickly released into circulation in times of
increased demand (left shift).
apperance of toxic change in the three sections
- Normal segmented (A) and late
band neutrophils (C), have white
cytoplasm with pink granules,
long and fairly narrow nuclei and
tightly condensed chromatin. - Segmented (B) and band
neutrophils (D) with toxic change
have less condensed chromatin
than their normal counterparts
and bluer cytoplasm due to
retention of ribosomal RNA. - Doehle body (ribosomal protein
aggregate – arrow) in Band Cells
is considered toxic change (E)
stress leukograms - what happens when animals are stressed, why does it happen, what is it accompanied by, what induces it
Often in cases where an animal is stressed by exercise or
the act of restraint/blood collection, the numbers of mature
neutrophils increases in the blood. (Neutrophilia without a
left shift).
- This is due to mobilization of the “marginated” pool of
neutrophils in the blood vessels – there is no increase in the
band cells present and no toxic changes. - It is usually accompanied by a decrease in the numbers of
lymphocytes and an increase in the numbers of monocytes. - It is thought to be induced by cortisol and epinepherine and
is considered to be a normal or non-specific change in many
cases
life cycle of monocytes and macrophages - circulation and %, why does a monocyte convert, what are monocytes attracted to, can macrophages divide and how do they adapt
Monocytes circulate in the bloodstream and represent ~5% of
WBC numbers. Like neutrophils, they are ultimately destined to
leave the blood and enter tissue to act as resident immune cells
or in response to infections or tissue damage.
- When a monocyte enters damaged tissue through the
endothelium of a blood vessel, it undergoes a series of changes
to become a macrophage - Monocytes are attracted to a damaged site by chemical
substances (cytokines, chemokines) through chemotaxis - Macrophages are unable to divide, they perform differentiated
functions related to pathogen clearance and removal of dead
cells and debris
macrophage life cycle - attraction process, how long is the life span, when do they fuse
The stimuli that attract monocytes include damaged cells, pathogens, histamine released by mast cells and basophils, and cytokines released by macrophages already at the site
- Unlike short-lived neutrophils, the life span of a macrophage ranges from months to years
- Sometimes macrophages fuse to form giant cells, commonly seen in tuberculosis and other granulomatous diseseases (Actinobacillus, Actinomyces)
functions of macrophages - (5) and components involved
Phagocytosis (essentially like neutrophils) and Microbicidal Activity
- Scavenger Role – Cellular remnants, apoptotic cells, lipids, etc.
- Regulation of immune response (“presents” antigens to lymphocytes to activate the immune response).
- Cytotoxicity – Direct killing of tumor and infected cells (perforins etc.) (Degranulation)
- Secretory Role – cytokines, granule contents, clotting factors (Degranulation).
resident macrophages in tissues - where are alveolar macrophages, microglia, kuffer cells, histiocytes and osteoclasts located
lungs
brain
liver
connective tissue
bone
eosinophils - % present, primary role, other tasks they have been associated with
Comprise 1-4% of total WBC numbers.
- Primarily appear responsible for combating parasitic infection in the body
- They have also been widely implicated in allergy and asthma as their granules, when released, cause some of the associated respiratory and skin signs (edema, itching, congestion)
eosinophil granules - two branches and then if they have subsets within
histamine and proteins
proteins include: major basic protein, RNAse, DNAse, plasminogen, lipase
functions of eosinophils - two categories and details within
Phagocytosis and Bactericidal Activity
* Eosinophils can phagocytose wide variety of substances,
including bacteria, yeast, antibody coated RBCs, mycoplasma
and mast cell granules
- Eosinophils are less efficient in phagocytosis and killing of
bacteria compared to neutrophils
Parasiticidal Activity
PARASITICIDAL ACTIVITY
* Direct phagocytosis of parasites by eosinophils is not involved,
instead, eosinophils release granule contents when in contact with the antibody coated (opsonized) parasites. Kill by oxidation of parasite membranes.
- Protective antiparasitic immunity by esoniophils has been observed against numerous different parasites
eosinophelia - when is it seen, how is it occasionally observed
Typically seen in cases with a parasitic infestations
- Also found in some cases of rheumatoid arthritis, extensive
skin diseases, and with the use of certain drugs such as
penicillin. - Occasionally observed as an idiopathic infiltrate in muscle
(eosinophilic myositis) or lung (pulmonary infiltrate with
eosinophils)
eosinopenia - what is it, when does it occur, reason for drop in numbers, what is it also a feature of
Eosinopenia is a decrease in eosinophil number.
- Occurs when glucocorticoids are administered or rise endogenously (Cushing’s, Stress)
- The reason for drop in numbers is a redistribution of eosininophils into capillary beds with longer term
decreases in production - Eosinopenia is also a feature of hyperadrenocorticism because of increased endogenous corticosteroid concentration
basophils - how common, what do they store, recruitment
Basophils are the least common of the granulocytes, representing about 0.5% to 1% of circulating leukocytes. Specific roles not well understood.
- Store histamine, which causes some of the symptoms of an
allergic/anapylactic reaction. Similar in many ways to Mast Cells in tissue. - Like all circulating granulocytes, basophils can be recruited out of the blood into a tissue when needed
functions of basophils - what role do they play, what are the granules rich in, what do they recruit to inflammed sites
- Basophils play a role in immune mediated inflammation,
especially in analphylaxis and cutaneous hypersensitivity - Granules of basophils are rich in histamine, heparin, sertonin and hyaluronic acid
- Basophils produce eosinophilic chemotactic factor that attract eosinophils and neutrophils to inflammed sites
basophilia - how common, associated with what, what is it also associated with in dogs, why is basopenia not recognized
Increase in basophil numbers are rarely numerically dramatic
- Basophilia is associated with the diseases causing increased IgE production
- In dogs, basophilia is commonly associated with heartworm infestation
- “Basopenia” is not recognized because normal numbers are so low that absence on a CBC is not
notable
