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IMMUNOLOGICAL ASPECT OF BACTERIAL INFECTION

IMMUNOLOGICAL ASPECT OF BACTERIAL INFECTION. Dr A.Aziz Djamal MSc.DTM&H.SpMK (K). Bacterial Infection. Colonization of pathogenic bacteria on / inside the body which are potentially harmful to our body. Immunosurveillan system of our body will recognize invading bacteria. WHY

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IMMUNOLOGICAL ASPECT OF BACTERIAL INFECTION

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  1. IMMUNOLOGICAL ASPECT OF BACTERIAL INFECTION Dr A.AzizDjamalMSc.DTM&H.SpMK(K)

  2. Bacterial Infection Colonization of pathogenic bacteria on / inside the body which are potentially harmful to our body

  3. Immunosurveillan system of our body will recognize invading bacteria WHY Genetically different. Bacteria contain many structurally non-self substances. Bacteria produce many antigenic products

  4. Bacterial components are excellent activator of Innate Antigen-Non Specific immune response

  5. Direct Activators Lipopolysaccharide (Endotoxin) Lipoarabinomannan. Lipoteichoic acid Glycolipids and Glycopeptide. Polyanions N-formyl peptides

  6. Act as Chemotactants Peptidoglycans fragments Cell Surface activation of alternating pathway of the complement ( C3a and C5a )

  7. Activation of Antibacterial immune Response Peptidoglycanlayer of Gram (+) bacteria and Lipopolysaccharides layer of Gram (-) bacteria Activate the alternative pathway (properdin) of complement in the absence of antibody. Activate the Classical pathway of complement via mannose binding protein (MBP). Recognize by Pattern-recognized receptors including Toll-Like receptors on Macrophage and Dendritic cells—activate the protective immnune response

  8. Lipopolysaccharide – LPS / Endotoxinis a strong activator of :MacrophageB CellsOthers ( endothelials cells)

  9. Activation of Complement ( both pathways ) Very early and important antibacterial immune response Complement activate the inflammatory response Complement can directly kill Gram (-) bacteria.

  10. Activation of complement cascade by Gram (+)/Gram (-) Bacteria provide the following protective immune responses 1.Chemotactic factor (C5a) attract Neutrophil and Macrophage to the infection site. 2. Anaphylatoxin (C3a and C5a) Stimulate releasing of histamin by macrophage – increasing vascular permeability- increase access to the infection site. 3. Opsonin (C3b) bind to bacteria and promote phagocytosis. 5. B-Cells activator (C3d)

  11. Activation of Classical cascade of Complement Usually occur later in bacterial infection and it is activated by the presence of antibody IgM or IgG and it will activate the whole complement system

  12. Other Non Specific Protective Immune Effectors Kinins and Clotting Factors : produced by tissue damage, involve in inflammation, increase vascular permeability and chemotactors for leucocytes. Metabolic Product of Arachidonic acid: Prostaglandin and Leukotriens, mediates every aspect of inflammation

  13. Phagocyte and Phagocytosis The first cells to appear in acute infection : 1.Polymorphonuclear Neutrophils (PMN) 2.Monocyte 3. Eosinophyl ( Occasionally ) Followed later by Macrophage

  14. Neutrophils PMN that provide the antibacterial response. Attracted to the site of infection, phagocytized and killed internalized bacteria. Increase number of neutrophils in blood, body fluid or tissue indicate bacterial infection. Mobilization of neutrophils will followed by “a left shift” accumulation of the immature “band form”

  15. Phagocytosis of Bacteria by Macrophage and Neutrophils involved several process Attachment. Internalization. Digestion

  16. Attachment Receptor for bacterial carbohydrate: Lectin (specific sugar binding protein) Receptors for opsonins (C3b receptor, MBP receptor). Fibronectin receptor , Specific for S. aureus. Fc receptor for antibody.

  17. Internalization After the attachment, the bacteria will be surrounded by a portion of plasma membrane and formation of phagocytic vacuole that surrounding the bacteria

  18. Digestion It is fusion of vacuole containing bacteria with the primary lysosome (Macrophage ) or Granules (PMN) followed by inactivation / destruction of vacuole content. It is a very complex processes involving many factors and substances : Oxygen-dependent Oxygen-independent Depend on antimicrobial release by granules

  19. Digestion will be greatly enhanced by activation of Macrophage by many substances 1.Interferon ( Inf-gamma,the best ). 2.GM-CSF 3.TNF-alpha. 4.Lymphotoxin (TNF-beta)

  20. Oxygen dependent Hydrogen peroxidase (NADPH Oxydase and NADH oxydase. Superoxydase. Hydroxyl radicals (OH). Activated halides ( Cl, I, Br ). Myeloperoxidase Nitrous oxyde.

  21. Oxygen independent 1.Acids Lysozymes ( degrade bacterial peptidoglycan) Lactoferrin ( Chelate iron ). Defensins and other cationic proteins ( damage membrane ). 5. Proteases, Elastases and cathepsin G

  22. If the above non-specific protective immune response succeeded in eliminating the invading bacteria the process is finished If it is failed, the processed will proceed to the specific protective immune response and most of the phagocytic cells especially Macrophage and Dendritic cells will act as Antigen Presenting Cells / APC

  23. The Specific Protective Immune response will be divide into : Humoral Cellular Depend much on the kind of bacteria whether it is extracellular or intracellular bacteria

  24. Extracellular bacteria the clearance will mostly depend on humoral protective immune response Intracellular Bacteria their clearance will mostly decided by the cellular immune response

  25. Thank You

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