Phagocytosis Lecture Notes PDF

Immunology HML2053 1 1 LO2: Describe the non-specific defense (innate) mechanism of the host Week 6: Define phagocytosis and describe the process. 2 RECAP  RECAP: Summery of Immunity Innate (natural) Immunity:...

Immunology HML2053 1 1 LO2: Describe the non-specific defense (innate) mechanism of the host Week 6: Define phagocytosis and describe the process. 2 RECAP  RECAP: Summery of Immunity Innate (natural) Immunity: First & second line of defense against infection, born with, always present, non-specific, not dependent on prior exposure, available at short notice to protect from invaders. Acquired (Adaptive) Immunity: Third line of defense, develops slowly, more specialized, produces a specific response to each infectious agent, remembers that agent & can prevent disease later.  2nd Line of defense Pathogens able to penetrate the first line of defense are usually destroyed by non-specific cellular & chemical responses, collectively referred to as 2nd line of defense. These involve: 1. Phagocytosis 2. Inflammation 3. Production of fever 4. Production of interferons 5. Activation of complement system  Phagocytosis Definition: The process of ingestion of a microorganism or any particulate matter by a cell “phagocyte” Phago: eat / -Cyte: cell  from Greek Ingestion of microbes or particles by a cell, performed by phagocytes. How these cells involved: 1. Neutrophils: Phagocytic 2. Basophils: Produce histamine 3. Eosinophils: Toxic to parasites & some phagocytosis 4. Dendritic cells: Initiate adaptive immune response (APC) 5. Monocytes: Phagocytic as mature macrophages Fixed macrophages: in lungs, liver & bronchi Wandering macrophages roam tissues 6. Lymphocytes: Involved in specific immunity  Phagocytosis Three essential features of phagocytic cells are: 1. Actively phagocytic 2. Contain digestive enzymes to degrade ingested material. 3. Important link between innate & acquired immunity. (Antigen Presenting Cells “APC”)  Phagocytosis A) GRANULOCYTES (NEUTROPHILS): B) MONOCYTES / MACROPHAGES: Dominant WBC in bloodstream, Reside in tissues, mature from short-lived, NOT present in normal circulating monocytes that migrate later healthy tissue. into tissue. Large no. in connective tissues specialized ones are: Have three types of granules: 1. Kupffer cells in liver 1. Azurophilic granules 2. Alveolar in lungs (myeloperoxidase, some lysozyme & a family of cationic proteins) 3. Mesangial cells in glomeruli 2. Specific (lactoferrin, lysozyme & a 4. Microglia in brain B12-binding protein) 5. Osteoclasts in bones 3. Tertiary (conventional lysosomes 6. Histiocytes in connective tissue. with acid hydrolysis) 7. Synovial macrophages in joints  Mechanism of phagocytosis Divided into four main phases: Chemotaxis, adherence, ingestion & digestion. http://highered.mcgraw-hill.com/classware/ala.do?isbn=0072965630&alaid=ala_1320899&showSelfStudyTree=tr ue  1. Chemotaxis: It is the chemical attraction of phagocytes to microorganism. Neutrophils come to the site ‘first & fast’ Phagocytic cells must be attracted to the site of infection. How!! By chemotactic factors include: 1. Products of injured tissue 2. Factors from blood (C5a) 3. Substances produced by neutrophils & mast cells (leukotrienes & histamine) 4. Bacterial products (formyl-methionine peptides).  2. Adherence: It is the attachment of the phagocyte’s plasma membrane to the surface of the microorganism or any foreign material. Opsonization: is the coating of particles/ pathogens by substances like immunoglobulin, complement components & fibronectin. Like ‘butter on the bread’ Phagocytic cells both have receptors for Fc portion of certain Ig & C3 component of the complement system. So, recognition & binding of opsonized particles & then ingestion.  3. Ingestion: It is the plasma membrane of the phagocyte extends projections called pseudopods that engulf the microorganism Once the microorganism is surrounded, the pseudopods meet & fuse to form (phagosome). This is accompanied by :↑ glycolysis &↑ synthesis of proteins & membrane phospholipids.  3. Ingestion: Cells undergo metabolic changes with the aid of enzymes: O2 consumption ↑ (respiratory burst) of molecular O2 to high reactive intermediates, e.g. generation of singlet oxygen, superoxide anion (O-2) & release of H2O2. All have microbactericidal activity O2- dependent killing mechanisms.  4. Digestion: Phagosome pinches off from plasma membrane & enters cytoplasm where it contacts lysosomes that contain digestive enzyme & bactericidal substances. Upon contact, phagosome & lysosome membranes fuse & form a singular larger structure “Phagolysosome”  5. Killing Killing is by a: 1. O2-dependent mechanism: superoxide anion, H2O2, singlet O2 & hydroxyl radicals are all microbicidal 2. O2-independent mechanisms: low pH, lysozyme & lactoferrin all microbicidal  6. Exocytosis: Exocytosis: Killed organisms are digested by hydrolytic enzymes & degradation products released to exterior. Summary of phagocytosis  Activity! Define “Phagocytosis”? Draw the process of phagocytosis then label all the main phases?  References Turgeon, Mary Louise. (2018) Immunology and serology in laboratory, 6th ed. ISBN 9780323402873 Levinson, Warren E, (2016). Review of Medical Microbiology and Immunology, 14th ed. McGraw-Hill. ISBN: 9781307198379 Abbas, Abul K./ Lichtman, Andrew H. (2011). Cellular and molecular immunology (with student consult online access) (7th Revised ed./e). Elsevier Health Sciences. ISBN: 9780808924258 Eales, L. J. Immunology for life scientists. John Wiley. 1997. ISBN: 0471962252. Playfair, J. H. I. / Chain, B. H. Immunology at a glance. Blackwell Science. 2001. ISBN: 0632054069. Sompayrac, Lauren M. How the immune system works. Blackwell Science. 1999. ISBN: 0632044136. 800 MyHCT (800 69428) [email protected] www.hct.ac.ae Happiness Center PO Box 25026 Abu Dhabi, UAE HCT_UAE hctuae 20