neutrophil.pptx

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1. Neutrophils Presented by : Farah Al-amleh Supervised by : Dr.Izz Aldin Eqtiti

2. Outlines 1- Introduction. 2- hematopoiesis. 3- Neutrophil . 4- Neutrophilia. 5- Neutropenia.

3. Blood components

4. Blood components

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)

7. Hematopoiesis

8. Hematopoiesis

9. Hematopoiesis

10. Growth factors for hematopoiesis

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.

16. Neutrophils

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

22. Functions of neutrophils

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. 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

26. Neutropenia Neutropenia: < 51% or < 1500/mm3 Mild: 1,000–1,500 cells/mm3 Moderate: 500–1,000 cells/mm3 Severe: < 500 cells/mm3 (characterized by severe infections; see “Agranulocytosis”) Causes: Bone marrow damage/suppression (e.g., aplastic anemia, chemotherapy, radiation) Drugs (e.g., carbimazole, clozapine) Autoimmune diseases (e.g., SLE, Crohn disease, granulomatosis with polyangiitis) Rarely: bacterial infection (e.g., typhoid fever, sepsis, postinfectious state) Immune deficiencies (e.g., Kostmann syndrome) Viral infections (e.g., hepatitis, EBV infection) Benign ethnic neutropenia (not pathological)

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