Ministry Of Higher Education Faculty Of Medicine Bani Suef University

: Research On Neutrophils : Prepared By Abdullah Ghareeb -1 Abdulrahman Saad -2 Mohammed Khamis -3 Abdulrahman Shaban -4 Marco Ashraf -5 : Under Supervision Of [Link]

:Contents

Definition -1 2- Characteristics 3- Life Span 4- Chemotaxis 5- Anti-microbial Function 6- References

:Definition

Neutrophils, which are produced in the bone marrow and circulate in the blood, are a type of white blood cell. Neutrophils, are abundant and make up about 50% to 75% of white blood cells. Neutrophils respond to infection and attack bacteria and other foreign invaders directly. Neutrophils are the first type of immune cells to respond to and arrive at the site of infection, often within an hour. Neutrophils will not only respond to infections inside the body, but also on the surface, as in the case of skin infections. Pus, which is one visible sign of a skin infection, contains mainly dead neutrophils, bacteria, and cells. Pus can form internally, as well.( Witko-Sarsat etal., 2000) Neutrophils are the most abundant white blood cells in humans (approximately 1011 are produced daily); they account for approximately 50-70% of all white blood cells (leukocytes). The stated normal range for human blood counts varies between laboratories, but a neutrophil count of 2.57.5 x 109/L is a standard normal range. People of African and Middle Eastern descent may have lower counts, which are still normal . ( Edwards and Steven W., 1994)

: Characteristics
Neutrophil granulocytes have an average diameter of 1215 micrometers (m) in peripheral blood smears. When analyzing a pure neutrophil suspension on an automated cell counter, neutrophils have an average diameter of 89 m. With the eosinophil and the basophil, they form the class of polymorphonuclear cells, named for the nucleus's multilobulated shape. The nucleus has a characteristic lobed appearance, the separate lobes are connected by chromatin. The nucleolus disappears as the neutrophil matures, which is something that happens in only a few other types of nucleated cells. In the cytoplasm, the Golgi apparatus is small, mitochondria and ribosomes are sparse, and the rough endoplasmic reticulum is absent. A minor difference is found between the neutrophils from a male subject and a female subject. The cell nucleus of a neutrophil from a female subject shows a small additional X chromosome structure, known as a "neutrophil drumstick". When circulating in the bloodstream and unactivated, neutrophils are spherical. Once activated, they change

shape and become more amorphous or amoeba-like and can extend pseudopods as they hunt for antigens. ( Edwards and Steven W., 1994)

:Life Span
The average lifespan of (non-activated human) neutrophils in the circulation is about 5.4 days. Upon activation, they marginate (position themselves adjacent to the blood vessel endothelium), and undergo selectin-dependent capture followed by integrin-dependent adhesion in most cases, after which they migrate into tissues, where they survive for 12 days. Neutrophils are much more numerous than the longer-lived monocyte/macrophage phagocytes. A pathogen (diseasecausing microorganism or virus) is likely to first encounter a neutrophil. Some experts hypothesize that the short lifetime of neutrophils is an evolutionary adaptation. The short lifetime of neutrophils minimizes propagation of those pathogens that parasitize phagocytes because the more time such parasites spend outside a host cell, the more likely they will be destroyed by some component of the body's defenses. Also, because neutrophil antimicrobial products can also damage host tissues, their short life limits damage to the host during [Link] will often be phagocytosed themselves by macrophages after digestion of pathogens. ( Pillay J etal., 2010)

:Chemotaxis
Neutrophils undergo a process called chemotaxis, which allows them to migrate toward sites of infection or inflammation. Cell surface receptors allow neutrophils to detect chemical gradients of molecules such as interleukin-8 (IL-8), interferon gamma (IFN-gamma), C5a, and Leukotriene B4, which these cells use to direct the path of their [Link] have a variety of specific receptors, including complement receptors, cytokine receptors for interleukins andinterferon gamma (IFN-gamma), receptors for chemokines, receptors to detect and adhere to endothelium, receptors for leptins and proteins, and Fc receptors for opsonin. (Charles N. Serhan etal., (2010)

:Anti-microbial Function

Being highly motile, neutrophils quickly congregate at a focus of infection, attracted by cytokines expressed by activated endothelium, mast cells, and macrophages. Neutrophils express and release cytokines, which in turn amplify inflammatory reactions by several other cell types. In addition to recruiting and activating other cells of the immune system, neutrophils play a key role in the front-line defence against invading pathogens. Neutrophils have strategies for directly attacking micro-organisms: phagocytosis (ingestion), release of soluble antimicrobials (Degranulation)
A) Phagocytosis

Neutrophils are phagocytes, capable of ingesting microorganisms or particles. For targets to be recognised, they must be coated in opsonins a process known as antibody opsonization. They can internalize and kill many microbes, each phagocytic event resulting in the formation of a phagosome into which reactive oxygen species and hydrolytic enzymes are secreted. The consumption of oxygen during the generation of reactive oxygen species has been termed the "respiratory burst", although unrelated to respiration or energy production. The respiratory burst involves the activation of the enzyme NADPH oxidase, which produces large quantities of superoxide, a reactive oxygen species. Superoxide decays spontaneously or is broken down via enzymes known as superoxide dismutases, to hydrogen peroxide, which is then converted to hypochlorous acid HClO, by the green heme enzyme myeloperoxidase. It is thought that the bactericidal properties of HClO are enough to kill bacteria phagocytosed by the neutrophil, but this may instead be a step necessary for the activation of proteases.
B) Degranulation

Neutrophils also release an assortment of proteins in three types of granules by a process called degranulation. The contents of these granules have antimicrobial properties, and help combat infection.( Segal, AW (2005)) The image source : Barbara Young etal.,) (2006

: References
Barbara Young , James S. Lowe , Alan Stevens , John W. Heath , Philip -1 J. Deakin .Wheater's Functional Histology: A Text and Colour Atlas, 5th Edition 23:164 , 2006

Charles N. Serhan, Peter A. Ward, Derek W. Gilroy -2 (2010). Fundamentals of Inflammation. Cambridge University Press. pp. 5354

Edwards, Steven W. (1994). Biochemistry and physiology of the -3 neutrophil. Cambridge University Press. pp. 6

Pillay J, Borghans JA, Tesselaar K, Koenderman L. In vivo labeling of -4 .a human neutrophil lifespan of 5.4 days. 2010 Jul 29;116(4):625-7

Segal, AW (2005). "How neutrophils kill microbes". Annu Rev -5 .Immunol 9 ((5)): 197223

Witko-Sarsat, V; Rieu P, Lesavre P, Halbwachs-Mecarelli L -6 (2000)."Neutrophils: molecules, functions and pathophysiological .aspects". Lab Invest 80 (5): 61753