Neutrophils Flashcards
What is the primary function of neutrophils?
phagocytosis and bactericidal action
What processes are necessarry for the phagocytotic and bactericidal functions of neutrophils?
stickiness for emigration through vessel walls; chemotaxis - motile response toward an attractant in tissue; ingestion/degranulation; bacteriocidal action
What may neutrophil function be compromised by?
deficiency of various humoral/cellular components; drug actions; toxic bacterial products
What are the secondary functions of neutrophils?
secretion of endogenous pyrogen when exposed to bacteria/bacterial products; contribute to pathology of certian conditions - ex. immune complex glomerulonephritis, rheumatoid arthritis
Define septecemia.
Bacteria in the bloodstream.
Define bacteremia.
Bacteria in the bloodstream.
Define diapedesis.
the process of a neutrophil passing through the endothelium of the blood vessels and into the tissues of the body
What is the fourth stage of neutrophil production?
myelocyte
What is the third stage of neutrophil production?
promyelocyte
What is the second stage of neutrophil production?
myeloblast
What is the progenitor cell type for neutrophil production?
stem cell
What are the three types of myelocytes?
neutrophillic, eosinophillic, basophilic
How are the three different types of myelocytes identified?
The three types of myelocytes are identified by the presence of specific granules in the cytoplasm
What is the fifth stage of neutrophil production?
metamyelocytes
What is the sixth stage of neutrophil production?
neutrophilic band
What is the seventh stage of neutrophil production?
neutrophilic segmenter
What is the first stage that a neutrophil cell line progenitor can be distinguished?
myelocyte
How many divisions occur during neutrophil production?
five points of division - myeloblast (one division), promyelocyte (one division), and myelocyte (about three divisions)
How many days supply of neutrophils does the body store?
In health there is about a five day supply of neutrophils in storage.
What is a neutrophilic left shift?
A neutrophilic left shift occurs during periods of increased need. When mature neutrophils in stroage are depleted, progressively younger cells are released into the blood.
WHat are the mechanicms for increased neutrophil production?
increased stem cell input; increased effective granulopoiesis in proliferation/maturation
When does increased stem cell input occur?
at the earliest demand for neutrophils
How many days from increased stem cell input until a difference is seen in blood neutrophil numbers?
4-5 days
What steps are taken to increase effective granulopoiesis in proliferation and maturation?
additional divisions; normal myelocyte attrition decreased
When may a sustained neutrophilia be noticed?
2-3 days after initial stimulus
What is neutrophil production regulated by?
granulopoietin
What is another term used to refer to granulopoietin?
CSF - colony stimulating factor
Where is granulopoietin produced?
granulopoietin is produced in the bone marrow by bone marrow macrophages
What is the stimulus for granulopoietin stimulus?
presence of bacterial products
What is the function of granulopoietin?
it is absolutly required to stimulate the mitosis of stem cells, and affects the number of divisions of any cell in the maturation series
What is neutrophil release from the bone marrow promoted by?
plasma factor or leukocytosis-inducing factor - LIF
What is LIF concentration increased by?
LIF is increased by bacterial products and in certian neutropenic disorders (origin unknown)
What is the reason for rapid neutrophilia (<2 days)?
increased rate of release
In health what are normal neutrophil kinetics?
neutrophils move slower than red blood cells and plasma through venules resulting in uneven distribution, and they hesitantly adhere to the endothelium of the vessels. these cells are not included in WBC count
What is the marginal neutrophil pool?
neutrophils adhered to the endothelium of the vessels and not included in the WBC count
What is the circulating neutrophil pool?
cells moving with the red blood cells and plasma - the neutrophil count in WBC count
In the dog, how much of the total neutrophil supply is in circulation?
about half - CNP = MNP
In the cat, how much of the total neutrophil supply is in circulation?
1/4 - MNP is about 3x> CNP
What is the average neutrophil transit time?
10 hours
How often is the body’s neutrophil supply replaced?
about 2.5 times a day
How are neutrophils lost in health?
through secretions, excretions and mucous membranes
What is an epinephrine induced neutrophilia caused by?
An epinephrine induced neutrophilia is caused by mobilization of the MNP cells
What is physoilogic neutrophilia caused by?
epinephrine (stress)
What is the transit time of an epinephrine induced neutrophilia?
20-30 minutes after the release of epinephrine
What are some things that can cause stress that results in a physiologic neutrophilia?
fear, exercise, excitement, rough handling, strange surroundings, hypertension, seizures, parturition
Can a physiologic neutrophilia be seen in healthy animals?
yes
What types of neutrophils are not increased in a physiologic leukogram?
band neutrophils
What are the characteristics of a corticosteroid induced neutrophilia?
transit time in circultion increased, bone marrow release rate increased
Are immature forms of neutrophils seen in corticosteroid induced neutrophilia?
If the body’s storage pool is adequate immature forms are not released
Why do corticosteroids cause a neutropilia?
Corticosteroids decrease neutrophil stickiness and an increase in the percentage of CNP.
What induces the release of corticosteroids?
pain, anesthesia, surgical manipulation, trauma, noninflammatory cachetic disorder, neoplasia and hyperadrenocorticism (Cushing’s)
What may be an indicator of stress accompanying an inflammitory disorder?
lymphopenia
How long does it take a dose of exogenous corticosteroids to cause a corticosteroid neutrophilia?
within 4-8 hours of a single dose
How long does it take for the leukogram to return to normal after the administration of exogenous corticosteroids?
12-24 hours
In patients who have been administered corticosteroids long term, how long does it take to return to a normal leukogram following the cessation of treatment?
48-72 hours
What is the magnitude of neutrophilia in inflammitory disease determined by?
magnitude is determined by the balance between the rate of bone marrow release and the rate of tissue emigration
If the rate of bone marrow release is highter then the rate of tissue emigration, what is the result?
neutrophilia
What is the result of a rate of tissue emigration that is higher then the rate of bone marrow increase?
neutropenia
What is the appropriate physiologic response to increased tissue demand for neutrophils?
a “left shift” as progressively more neutrophils enter the blood
What results indicate that tissue demand is exeeding supply?
immature neutrophls >/= mature neutrophils
What can a left shift without neutrophilia indicate?
tissue demand may be overwhealming
How can overwhelming tissue demand be adequately accomidated by the body?
increased bone marrow production and release rate
What does the magnitude of an inflammitory neutrophilia vary with?
species, location of inflammation, virulence and inciting cause
Which inflammation location elicits a greater response?
localized purulent inflammation elicits a greater response then generalized inflammation ex. pyymetra>septicemia
What causes can cause a greater response?
pyrogenic agents and tissue necrosis
Occasionally neutrophilia persists following removal of the inciting cause - why?
bone marrow response hasn’t yet decreased but the tissue demand is eliminated
Define excessive usage neutropenia.
neutropenia caused by overwhealming tissue demand for phagocytes
What are characteristics of an excessive usage neutropenia?
neutropenia is marked - transit time decreased due to the tissue emigration rate being greater than the bone marrow release rate
What form of neutrophils comprise the highest proportion of all PMNs in circulation?
immature neutrophils
What is the usual cause of an excessive usage neutropenia?
peracute pyogenic bacterial infections
Define decreased production neutropenia.
neutropenia caused by granulopoietic hypoplasia
What are characteristics of a decreased production neutropenia?
decreased bone marrow production/release with normal emigration
What is the usual cause of a decreased production neutropenia?
Disorders of insidious onset and prolongued course.
usually serious disorders/secondary infection likely
Define neutroenia caused by ineffective granulopoiesis.
neutropenia in the presence of myeloid hyperplasia
What is an example of a disease causing neutropenia caused by ineffective granulopoiesis?
FeLV positive cat
Define sequestration neutropenia.
a neutropenia of sudden, transient occurance. The neutrophils marginate, decreasing the circulating neutophil population and increasing the marginal neutrophil population.
How are monocytes distributed in the body?
Monocytes are derived from the bone marrow and circulate briefly before becoming macrophages in the tissues.
How can macrophages be distinguished from monocytes?
Macrophages contain more granules and proteolytic enzymes.
What are some characteristics of macrophages?
Macrophages survive long periods in the tissue and are capable of division. They are functioning phagocytes.
What are some examples of monocyte-derived macrophages?
Macrophages or histiocytes of exudates Pleural/peritoneal macrophages Pulmonary alveolar macrophages CT histiocytes Macrophages of spleen, LN’s, bone marrow Kupffer cells of liver
What are the functions of macrophages?
Macrophages are responsable for phagocytosis/diestion of particulate and cellular debris, synthesis of certian substances, processing foreign substances to a more antigenic form, and cellular immunity via delayed hypersensitivity.
What are some examples of substances synthesized by macrophages?
endogenous pyrogen, interferon, colony stimulating factor
Where does monocytopoiesis take place?
Monocyte precursors are derived from a stem cell, and are released into circulation directly from the promonocyte pool in the bone marrow.
What are normal monocyte kinetics in health?
In health, monocytes may be unevenly distributed. Average blood transit time is unknown in animals, 12 hours in man.
What are the causes of monocytosis?
Monocytosis can be corticosteroid-induced, or caused by disorders characterized by tissue demand for phagocytosis or conditions in which cellular immunity is potentiated.
How is a corticosteroid-induced monocytosis identified?
It is recognized by its associated with neutrophilia without left shift, lymphopenia and eosinopenia
How do monocytes respond to exogenous corticosteroids?
They respond the same as with endogenous c-steroids but return to normal within 24 hours post-tx.
When else may a monocytopenia be observed?
A monocytopenia may be observed during decreased production neutropenia.
Is monocytopenia a clinically useful feature of leukograms?
no
What are some examples of causes of monocytosis?
painful episodes; hyperadrenocorticism, supperation (body cavities, necrosis, internal hemorrage, hemolytic disease, immune mediated diseases, granulomatous disorders, and decreased production neutropenia
What is the function of eosinophils?
Eosinophils are attracted by the chemical mediators of immediate-type allergic or anaphylactic hypersensitivity and inhibit the function thereof.
When are the chemical mediators of immediate-type hypersensitivity?
These mediators are released from mast cells sensitized by an antibody during contact with a specific antigen?
What is the role of the eosinophil?
To restrain and modulate the response of chemical mediators being released by mast cells that have been sensitized by an antibody during contact with a specific antigen?
Where are eosinophils produced?
Eosinophils are produced in the bone marrow in a process very similar to that of neutrophil production.
What are normal eosinophil kinetics?
The blood transit time of eosinophils is 24-35 hours. Eosiniophilic stem cells are responsive to CSF, which is dependant on sensitized lymphocytes.
When is eosinophilia seen?
In cases of parasitism and in cases of probably Ag-Ab interaction in tissues rich in mast cells.
What are some examples of tissues rich in mast cells?
skin, lung, GI tract, female genital tract
When does eosinophilia occur in cases of parasitism?
Eosinophilia occurs in cases of parasitism where sensitization has occurred or the host/parasite contact is long and intimate.
What is eosinopenia generally attributed to?
Eosinopenia is generally attributed t the effects of corticosteroids.
What are the functions of basophils?
Basophils degranulate when antigen complexes with antibodies on their surfaces, a source of mediators of immediate-type hypersensitivity, and a source of heparin and plasma lipemia clearing agents.
What leukocyte produces heparin?
the basophil
How are basophils produced?
Basophil production parallels that of neutrophils.
What are normal basophil kinetics?
Basophils are sparse in most animals.
When may a basophilia might be seen?
Basophilia may be seen in cases of hyperlipemia or alongise eosinophilia during disorders of long-standing Ab stimulation for example, chronic heartworm disease.
What are characteristics of lymphocytes?
Only about 10% of lymphoctyes ever appear in blood. These cells are recirculated and most are t-lymphocytes. The vast majority remain in lymphoid tissue. Lymphocytes are long lived, capable of division and transformation to more active forms.
What are the two categories of lymphocytes?
The two categories of lymphocytes are t-lymphocytes and b-lymphocytes.
What are the characteristics of t-lymphocytes?
T-lymphocytes are emoryologically derived from the thymus and provide cell-mediated immunity.
What are the characteristics of B-lymphocytes?
B-lymphocytes are embryologically derived from bone marrow and provide humoral (antibody) immunity.
What are lymphocyte kinetics?
Lymphocytes recirculate
