5. Hematopoiesis
Hematopoiesis is the process by which multipotent hematopoietic stem cells
differentiate into either myeloid or lymphoid precursor cells and, eventually, into
mature blood cells.
- Myeloid precursor cells develop into erythrocytes, granulocytes, or
megakaryocytes.
- Lymphoid precursor cells develop into lymphocytes or natural killer cells.
6. Hematopoiesis
Location:
- Before birth: yolk sac, spleen, liver.
- After birth: Bone marrow
Potentially spleen and liver, e.g., in the case of severe chronic anemia and
some hematological malignancies (e.g., Hodgkin lymphoma)
11. Granulopoiesis
Definition: the process by which granulocytes develop from myeloid precursor cells.
Location: bone marrow.
Duration: 6 days,
Stages of development
pluripotent hematopoietic stem cell → common myeloid precursor cell → myeloblast →
promyelocyte → eosinophilic, neutrophilic, or basophilic myelocyte → metamyelocyte →
band cell → granulocyte (eosinophil/neutrophil/basophil)l
12. Granulopoiesis
(1) Myeloblast: round/oval nucleus with a very high nuclear-cytoplasmic (NC) ratio (i.e., a
large nucleus) and 2–5 prominent nucleoli. A thin blue cytoplasmic rim is visible.
(2) Promyelocyte: largest cell type that occurs during granulopoiesis; prominent nucleoli.
Dark (azurophilic, violet) granules (primary granules) can be seen in the cytoplasm.
(3) Myelocyte: nucleoli are no longer visible. The primary granules begin to be replaced
by secondary granules, resulting in a lighter cytoplasm.
(4) Metamyelocyte: bean-shaped nucleus. From this stage, secondary granules
predominate.
(5) Banded neutrophil: curved (banded) nucleus. The beginning of segmentation is visible.
(6) Segmented neutrophil: clearly segmented nuclei (held together by filamentous
chromatin bridges)
13. Granulopoiesis
The maturation process of the neutrophil lineage is characterized by:
- reduction in the size of the cell.
- development of granules containing agents essential for their microbicidal
function.
- The nucleus also gradually begins to adopt its characteristic segmented shape
14. Neutrophils
Characteristics:
- Neutrophils are the most common type of white blood cell and make up 54–
62% of all leukocytes in WBC count .
- Diameter: ∼ 12 μm.
- Half-life: 6–8 hours.
- Maturation: Band neutrophils (immature) develop into segmented neutrophils
(mature) over the course of 4–5 days.
- The multilobed nucleus contributes to the extreme elasticity of the cell, which
is important for the cell to make rapid transit from the blood through tight gaps
in the endothelium.
- Neutrophils are so named because of their neutral staining with Wright stain.
- They are also known as PMNs or polys or microphages.
15. Neutrophils
- The blood and bone marrow form an abundant pool of cells and
neutrophils are recruited and called to the sites of infection and
inflammation as and when required on stimulation by a cytokine.
- In the bone marrow, the myeloid precursor cells mature to segmented
neutrophils in about 9 days.
17. Functions of neutrophils
The mature neutrophil is a highly specialized cell specifically equipped for the
destruction of microorganisms.
- Adherence
- Chemotaxis
- Phagocytosis
- Microbicidal activity
- Oxidative Metabolism.
18. Functions of neutrophils
Adherence: When stimulated, the neutrophil interacts with, and sticks to,
substrate (endothelial cells) via specific molecules on the neutrophil and the
endothelial cell.
19. Functions of neutrophils
Chemotaxis — The granulocytes are attracted to the site of microbial insult in
response to specific chemotactic molecules such as complement proteins (C5a).
5-HPETE, LTB4, IL-8, C5a, kallikrein, and platelet-activating factor attract neutrophils
to the site of inflammation.
Phagocytosis — The neutrophil recognizes specific molecules on the bacterial
surface called opsonins (IgG, C3b) and engulfs the organisms via invagination of
the plasma membrane, which encloses the bacterium in a phagosome.
20. Functions of neutrophils
Microbicidal activity- It is of 2 types: intracellular killing and Extracellular killing.
- Intracellular killing: The membrane of the phagosome fuses with those of
cytoplasmic granules, resulting in the discharge of granule contents into the
phagosome, which is now termed a phagolysosome
The antimicrobial systems of the neutrophil include: oxidative ( oxygen free
radicals or lysosomal granules ) and non-oxidative mechanisms that result in
the death of the microorganism
21. Functions of neutrophils
- Extracellular killing: The same enzymes and agents that are discharged into
the phagosome may be secreted into the extracellular microenvironment.
This may contribute to extracellular killing of bacteria, but has the
disadvantage of potential damage to adjacent cells and tissues as many of
these enzymes are histiolytic, such as collagenase, elastase, and the reactive
oxygen species.
Immune mechanisms:
› Ab mediated lysis
› Cell mediated cytotoxicity
23. Absolute Neutrophil Count
Absolute Neutrophil Count (ANC) is the test to measure the number of neutrophils
present in a blood sample.
This test usually detects the total number of white blood cells which includes both mature
and immature neutrophils.
The neutrophil blood count breakdown neutrophils into two categories as segmented or
mature neutrophils and immature neutrophils or bands.
The neutrophil count is commonly conducted to detect abnormalities related to the
increase or decrease in the number of neutrophils.
The abnormal count of neutrophils is often associated with various medical conditions,
which makes this test an essential part of the laboratory examination of many diseases.
24. Absolute Neutrophil Count
ANC= Absolute mature neutrophils + absolute immature neutrophils
This test is performed to detect the presence of different organisms in the
bloodstream and also to detect if the immune system is working correctly.
ANC is usually performed as a part of the complete blood count to measure the
count of different blood cells.
25.
26. Neutrophilia
Neutrophilia: > 65%(An increase in circulating neutrophils does not necessarily
indicate increased production in the bone marrow; it can also result from the
mobilization of neutrophils normally adherent to vascular endothelium.)
Causes :
- Bacterial infections (especially pyogenic, due to, e.g., S. aureus, S.
pneumoniae).
- Inflammation (e.g., in burns, after myocardial infarction)
- Physical stress (e.g., surgery, exercise, generalized seizures)
- Drugs :Glucocorticoids: cause neutrophilia via demargination ,Catecholamines,
- Myeloproliferative neoplasms (e.g., CML)
- Smoking
- Asplenia
