PHAGOCYTOSIS

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PHAGOCYTOSIS- History • Introduction • Phases of phagocytosis :- a) Margination b) Diapedesis c) Chemotaxis d) Opsonization or Attachment e) Engulfment orIngestion f) Secretion or Degranulation g) Killing or Degradation • Applied Aspects • Recent Advances

1. PHAGOCYTOSIS DR.NABEEL BEERAN 1 st Year Physiology PG Moderator: Dr. SHANKAR BHAT 1

2. CONTENTS History Introduction Phases of phagocytosis :- a) Margination b) Diapedesis c) Chemotaxis d) Opsonization or Attachment e) Engulfment orIngestion f) Secretion or Degranulation g) Killing or Degradation Applied Aspects Recent Advances 2

3. Who discovered phagocytosis? Ellie Ilya Metchnikoff discovered it in 1882. Received Nobel prize for the same in 1906. Carl Fredrich Claus coined the term Phagocytosis . 3

4. Introduction Phagocytosis is a specific form of endocytosis . Phagocytosis (cellular eating) refers to the process of engulfment and destruction of solid particulate material by the cells. The cells performing phagocytosis are called phagocytes. The cell types mainly are: a) Neutrophils b) Monocytes c) Macrophages 4

5. Phases of Phagocytosis Margination 2. Emigration and diapedesis 3. Chemotaxis 4. Opsonization (attachment stage) 5. Engulfment stage 6. Secretion( degranulation stage) 7. Killing or degradation stage 5

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7. 1) Margination In the area of infection , the neutrophils gets marginated , i.e. get attached towards the capillary endothelium and start rolling along its surface. This process is called margination or pavementing . The margination is caused by binding of selectins (cell adhesion molecules) present on the endothelial cells with the carbohydrate molecules present on the surface of neutrophils . 7

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10. 2) Emigration and Diapedesis The marginated neutrophils are emigrated in large number from the blood to the site of infection. The process, by which neutrophils pass through the capillary endothelial cells to reach the invader in the tissue, is called diapedesis . 10

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12. 3) Chemotaxis Chemotaxis refers to the process by which the neutrophils are attracted towards bacteria at the site of inflammation. The chemical substances are released from the site of inflammation or infection by the infecting organisms or inflammatory cells. These chemical factors attract neutrophils to the site of infection and they are called chemotaxins . Leukotriene B4(LT-B4) and components of complement system(C5) and cytokines are some of the chemotaxins . 12

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15. 4) Opsonization or Attachment stage Opsonization refers to the process of coating of bacteria by the opsonins . The opsonin coated bacteria gets attached to the surface of phagocyte through the opsonin receptors. The principal opsonins are IgG opsonin and C3b opsonin . The attachment of membrane of phagocyte to the membrane of microbe is called adherence. 15

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19. 5) Engulfment or Ingestion The neutrophils project pseudopodia in all directions around the opsonized particle which is bound to the surface of neutrophil . Pseudopodia meet each other on opposite side and fuse; this creates an enclosed chamber with the engulfed material. It breaks away from the membrane forming a phagocyte vesicle. Then the lysosomes of the cell fuse with the phagocytic vesicle to form phagolysosome or phagosome . 19

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24. 6) Secretion or Degranulation stage Once the bacteria is engulfed, the lysosomes release their enzymes into the vesicle and also in interstitial space. This process is called degranulation . 24

25. 7) Killing or Degradation stage Several minutes after phagolysosome formation, the first detectable effect on the microorganism is the loss of the ability to reproduce. Inhibition of macromolecular synthesis occurs sometime later and many pathogenic and non-pathogenic bacteria are dead 10 to 30 minutes after ingestion. The killing mechanisms that phagocytes use can be organized into two broad groups: oxygen-dependent and oxygen-independent mechanisms . 25

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27. a) Oxygen independent killing mechanism Activation of Macrophages synthesizes the following: Lysozyme Defensins Tumor necrosis factor- α (TNF- α ) and Other hydrolytic enzymes 27

28. b) Oxygen dependent killing mechanism Activated phagocytes produce a number of Reactive Oxygen Intermediates (ROI) and Reactive Nitrogen Intermediate(RNI). When exposed to certain stimuli, phagocytes ( neutrophils , eosinophils & macrophages) oxygen uptake increase greatly, some times more than 50 folds; undergoes a series of changes “Respiratory Burst” 28

29. “Respiratory Burst” occurs during: Activation of macrophages during phagocytosis Abrupt rise in oxygen consumption Increase glucose consumption (HMP pathway) Large amount of ROI Activation of NADPH oxidase /phagocyte oxidase 29

30. Applied Aspects Disease Defect of Etiology Clinical consequences Chediak Higashi syndrome Degranulation AR; impaired coalescence of lysosomal granules. Neutropenia , recurrent pyogenic infections, oculocutaneous albinism. Leukocyte adhesion defect Adhesion AR; absence of CD11/18 surface adhesive glycoprotein. Neutrophilia , recurrent bacterial infections without pus. Chronic granulomatous disease Microbial killing AR/XLR defective NADPH oxidase . Recurrent pyogenic infections with catalase positive organisms( eg . S.Aureus ) Amyotrophic lateral sclerosis (ALS) Defective dismutase Genetic mutation of dismutase. Motor system disease; progressive degeneration of spinal motor neurons results in atrophy of skeletal muscles( amyotrophy ) Familial Mediterranean fever Increased cell motility AR; defective protein pyrin . Recurrent fever , serositis , arthritis and amyloidosis . 30

31. Recent Advances 31

32. THANK YOU 32