Leukocytes Flashcards
What 2 types of information does a leukogram give? What do abnormalities identify?
- WBC count
- WBC morphology
pathological processes without specific diagnosis
Leukocyte morphology:
MONOCYTES: large nucleus
NEUTROPHIL: segmented horseshoe nucleus
What is the leukon?
all WBC types in an animal including precursors and those in the blood, lymphatics, and tissue
What are the 2 types of mature WBC types? Where are the precursors found?
- polymorphonuclear - neutrophils, eosinophils, basophils
- mononuclear - monocytes, lymphocytes
(+ mast cells)
bone marrow
What is leukopoiesis? What are the 2 stem cell lines?
generation of WBCs from pluripotent hematopoietic stem cells of the bone marrow
- myelopoiesis (granulopoiesis) - derived from myeloid stem cells and give rise to eosinophils, basophils, neutrophils, and monocytes
- lymphopoiesis - derived from lymphoid stem cells to give rise to B and T lymphocytes
What do neutrophils contain? What are 2 characteristics of their morphology?
neutrally staining granules
- pale pinky cytoplasm
- constricted, multilobulated nucleus
What are heterophils? What do they look like?
neutrophil equivalents found in birds, rabbits, and reptiles
contain rod-shaped orange-pink granules
Neutrophils are relatively consistent across species. How are bovine and feline neutrophils unique?
BOVINE = brighter pink cytoplasm
FELINE = contain Dohle bodies, angular blue cytoplasmic inclusions
Feline neutrophil:
light blue Dohle bodies
What cytokines stimulate stem cells in the bone marrow to become myeloblasts? What are the 5 major steps to neutrophil maturation?
TNF-α and TNF-γ
- promyelocyte
- myelocyte (last mitotic division)
- metamyelocyte
- band neutrophil
- segmented neutrophil
What are the 4 neutrophil pools?
- proliferative pool (20% of bone marrow) - myeloblast, progranulocyte, myelocyte
- maturation and storage pool (80% of bone marrow) - metamyelocyte, band neutrophil, neutrophil)
- circulating and marginating pool - measured on CBC and adhered to endothelium
- tissues
From what neutrophil pool does a CBC measure?
circulating neutrophil pool
What makes a good approximation of the circulating neutrophil pool?
circulating neutrophil pool + differential count
What 2 neutrophil pools are not counted in the CBC?
- marginating neutrophil pool
- tissue netrophils
What is the general rule of marginating neutrophil pool count in dogs, horses, calves, and cats?
DOGS/HORSES/CALVES - MNP = circulating neutrophil pool
CATS - circulating neutrophil pool = 3x MNP
How can corticosteroids affect neutrophils?
causes neutrophils to be released from the marginating pool, which downregulates adhesion molecules responsible for margination and has the potential to double the mature neutrophil count
- stress leukogram!
What is the predominant leukocyte of health in most species? Ruminants?
neutrophils
lymphocytes
What is the half-life of neutrophils? How long do they survive in tissue? How are they destroyed?
5-10 hours in circulation, then egresses into tissue
24-48 hours
undergo apoptosis and are broken down by macrophages in the spleen, liver, and bones marrow
When are band neutrophils released into circulation? What is their morphology like?
in cases of overwhelming inflammation once the storage pool of segmented neutrophils is depleted
similar cytoplasm to mature neutrophils, but has a U- or S-shaped nucleus with few constrictions
What is the function of neutrophils/heterophils?
phagocytosis and defense against microorganisms using bactericidal granules
What is the normal morphology of eosinophils?
round cell with red-pink cytoplasm granules and multilobulated nucleus with constrictions
How does the morphology of eosinophils in cats, horses, and sighthounds differ?
- CATS = rod-shaped granules
- HORSES = large round granules
- SIGHTHOUNDS = gray granules
What species is this blood smear from? What are the arrows pointing to?
bird
- TOP = heterophil
- BOTTOM = eosinophil
What cytokines stimulate the maturation of eosinophils from stem cells in the bone marrow? What are the 5 stages of development?
IL-5 and IL-3 from mast cells, macrophages, and lymphocytes
- promyelocyte
- eosinophilic myelocyte
- eosinophilic metamyelocyte
- eosinophilic band
- eosinophil
How long do eosinophils remain in the blood? How long do they stay in tissue?
marginated and circulating pools remain in blood from minutes to an hour
last weeks and die in tissue
What is the rarest leukocyte in circulation in avian species?
eosinophils
What tissue do most eosinophils reside in? What is their function? What kind of hypersensitivity are they responsible for?
GI mucosa
helminth defense by releasing major basic proteins and generating toxic oxygen radicals
Type I hypersensitivity allergic reactions
What is the morphology of basophils?
contain granules that are round and dark purple, along with a multilobulated nucleus that is thin and ribbon-shaped
How do equine/bovine and cat basophils differ? What is true about dog and cat granules?
- EQUINE/BOVINE = numerous dark purple granules
- CATS = gray to lavender granules
more sparse granules compared to large animals
How many basophils are usually in circulation? What is their half-life like? What promotes their migration to tissue?
very low numbers
6 hours
inflammatory cytokines - survives around 2 weeks in tissue
What is contained in the granules of basophils? What is their function? What cytokines activate them?
most histamine measured in the blood
similar to mast cells - protective immunity against helminths
IL-3, IL-5
What are the 2 types of mononuclear cells?
- lymphocytes
- monocytes
What is the morphology of lymphocytes like? What can they contain in their cytoplasm? How do equine/bovine ones compare?
small round cells with large round nucleus and a high nuclear-to-cytoplasmic ratio
pink granules
larger, with more cytoplasm
What 3 cells do lymphoid progenitor cells give rise to? What are the source of most lymphocytes in adult mammals?
- B lymphocytes
- T lymphocytes
- natural killer cells
secondary lymphoid tisses: tonsils, LNs, spleen, BALT, GALT
What 3 things can happen to lymphocytes in tissues?
- blastogenesis
- return to blood via lymphatics
- die
How are lymphocytes able to recirculate? What is their half-life like?
leave lymph nodes via efferent ducts and enter blood via the thoracic duct
30 mins
What are the 2 major pools of lymphocytes
- circulating pool - only 2-5% of lymphocytes circulate in blood; 50-75% T, 10-40% B, 5-10% NK
- marginating pool
What is the general lymphocyte function? T-lymphocytes? B-lymphocytes?
defense against viruses and tumor cells, immunosuppression
cellular immunity - Th1, Th2
humoral immunity - produces antibodies
What are the largest WBCs? What is their morphology like?
monocytes - 2 to 4 times larger than mature RBC in diameter
light blue to gray cytoplasm with vacuoles and butterfly/kidney bean-shaped nucleus
What cytokines induce the maturation of monocytes? What are the 3 major steps? What are the reserves like in bone marrow?
IL-1, IL-3, IL-6
- monoblast
- promonocyte
- monocyte
faster production compares to granulocytes, but have little reserves in the marrow
What do monocytes do once they reach tissue? What are 5 examples?
differentiate into macrophages
- LIVER = Kupffer cells
- LUNGS = alveolar macrophages
- JOINTS = Type A synoviocytes
- CNS = microglial cells
- SKIN, LYMPHOID ORGANS = dendritic cells
What is the circulating half-life of monocytes? How long do they survive in tissue?
0.5-3 days
3 months - Langerhans cells in the skin can survive more than a year
What are 4 functions of monocytes/macrophages?
- phagocytosis of microorganisms, like fungi, helminths, and protozoa, RBCs, and extracellular material
- antigen presentation to T-lymphocytes
- source of cytokines (IL-1, IL-3, TNF) involved in inflammation and hematopoiesis
- tissue repair and remodeling
What is the morphology of mast cells like?
similar to basophils, with round, purple cytoplasmic granules, but have a circular (not multilobulated) nucleus
What cells are not routinely reported on CBC leukogram? What does this presence on a blood film indicate?
mast cells
pathology (inflammation or neoplasia) - enteritis, pleuritis, peritonitis, hypersensitivity reactions
Where do mast cells reside? Where do they mature> What are 2 functions they have?
sub-epithelial locations, like dermis, GIT submucosa, and in any tissues
tissues —> liver, spleen LN
- promote inflammatory reactions (hypersensitivity)
- fibrosis
What is neutrophil toxicity? What does it indicate? 4 examples?
morphological changes caused by increased neutrophil production and shortened maturation time in the bone marrow —> inflammation
- cytoplasmic basophilia
- cytoplasmic vacuolation (foamy)
- Dohle bodies
- ring form nuclei
What is happening in these blood smears?
A and C = normal mature and band neutrophil; white cytoplasm with pink granules, long and fairly narrow nuclei and tightly condensed chromatin
B and D = toxic change - less condensed chromatin and bluer cytoplasm due to retention of rRNA
What is happening in this blood smear?
neutrophil toxicity - Dohle bodies, blue cytoplasmic inclusions of remnant rER associated with left shift
- commonly seen with toxic granulation
What is the Pelger-Huet anomaly? In what 2 animals is this most common?
mutation in lamin B receptor gene leading to hyposegmentation of granulocytes - neutrophils look like bands or less mature forms
- Australian Shepherds
- Arabian horses
How does the CBC leukogram of animals with the Pelger-Huet anomaly present?
increased band or immature neutrophil count, typically with the animals being entirely healthy (doesn’t affect function of neutrophils)
- blood film helpful
What causes the formation of reactive lymphocytes? What 3 changes are seen?
cells proliferate due to antigenic stimulation, usually inflammation
- cytoplasm becomes larger and deeply basophilic with perinuclear Golgi clearing and vacuole formation
- increased cell size
- nucleus becomes variable in shape, less condensed, and may contain nucleoli
What is happening in these blood smears?
reactive lymphocytes - basophilia, visible nucleoli, increased cytoplasm
Ehrlichia in monocyte:
What bacteria are able to infect white blood cells? Monocytic? Granulocytic?
Anaplasmataceae spp.
- MONOCYTIC: Ehrlichia canis
- GRANULOCYTIC: Ehrlichia ewingii, Anaplasma phagocytophilum
How do monocytic Ehrlichia look within the WBC?
form a round morula
- Ehrlichia canis
What yeast commonly infects WBCs? What does it look like?
Histoplasma capsulatum
purple, spherical, clear halo infecting macrophages and monocytes
What are the 2 forms of Cytauxzoon felis that infect blood cells?
- SCHIZONTS in macrophages burst and release the apicomplexan protozoa
- MEROZOITES in RBCs
What is the characteristic morphology of Hepatozoon spp. infecting leukocytes?
capsular gamont
What forms of Toxoplasma spp. infect leukocytes?
can infect all warm-blooded animals with cats as DH and IH
tachyzoites infect host cells, causing it to burst and allow free tachyzoites to disseminate and reach other blood cells or tissue