immunological aspect of bacterial infection 2
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Immunological Aspect of Bacterial Infection 2Immunological Aspect of Bacterial Infection 2Immunological Aspect of Bacterial Infection 2Immunological Aspect of Bacterial Infection 2Immunological Aspect of Bacterial Infection 2Immunological Aspect of Bacterial Infection 2TRANSCRIPT
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IMMUNOLOGICAL ASPECT OF BACTERIAL INFECTION
Dr A.Aziz Djamal MSc.DTM&H.SpMK(K)
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Bacterial Infection
Colonization of pathogenic bacteria on / inside the body which are potentially harmful to our body
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Immunosurveillan system of our body will recognize invading bacteria
WHY1.Genetically different.2.Bacteria contain many structurally non-self substances.3.Bacteria produce many antigenic products
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Bacterial components are excellent activator of Innate
Antigen-Non Specific immune response
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Direct Activators
Lipopolysaccharide (Endotoxin)Lipoarabinomannan.Lipoteichoic acidGlycolipids and Glycopeptide.PolyanionsN-formyl peptides
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Act as Chemotactants
Peptidoglycans fragmentsCell Surface activation of alternating pathway of
the complement ( C3a and C5a )
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Activation of Antibacterial immune Response
Peptidoglycan layer of Gram (+) bacteria and Lipopolysaccharides layer of Gram (-) bacteria1.Activate the alternative pathway (properdin) of complement in the absence of antibody.2.Activate the Classical pathway of complement via mannose binding protein (MBP).3.Recognize by Pattern-recognized receptors including Toll-Like receptors on Macrophage and Dendritic cells—activate the protective immnune response
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Lipopolysaccharide – LPS / Endotoxinis a strong activator of :MacrophageB CellsOthers ( endothelials cells)
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Activation of Complement ( both pathways )
1. Very early and important antibacterial immune response
2. Complement activate the inflammatory response
3. Complement can directly kill Gram (-) bacteria.
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Activation of complement cascade by Gram (+)/Gram (-) Bacteria provide the following
protective immune responses1. 1.Chemotactic factor (C5a) attract Neutrophil
and Macrophage to the infection site.2. 2. Anaphylatoxin (C3a and C5a) Stimulate
releasing of histamin by macrophage – increasing vascular permeability- increase access to the infection site.
3. 3. Opsonin (C3b) bind to bacteria and promote phagocytosis.
4. 5. B-Cells activator (C3d)
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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
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Other Non Specific Protective Immune Effectors
1. Kinins and Clotting Factors : produced by tissue damage, involve in inflammation,
increase vascular permeability and chemotactors for leucocytes.
2. Metabolic Product of Arachidonic acid: Prostaglandin and Leukotriens, mediates
every aspect of inflammation
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Phagocyte and Phagocytosis
The first cells to appear in acute infection :1. 1.Polymorphonuclear Neutrophils (PMN)2. 2.Monocyte3. 3. Eosinophyl ( Occasionally )Followed later by Macrophage
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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”
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Phagocytosis of Bacteria by Macrophage and Neutrophils
involved several process
1. Attachment.2. Internalization.
3. Digestion
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Attachment1. Receptor for bacterial carbohydrate: Lectin
(specific sugar binding protein)2. Receptors for opsonins (C3b receptor, MBP
receptor).3. Fibronectin receptor , Specific for S. aureus.4. Fc receptor for antibody.
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Internalization
After the attachment, the bacteria will be surrounded by a portion of
plasma membrane and formation of phagocytic vacuole that surrounding
the bacteria
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DigestionIt 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-independentDepend on antimicrobial release by granules
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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)
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Oxygen dependent
Hydrogen peroxidase (NADPH Oxydase and NADH oxydase.Superoxydase.
Hydroxyl radicals (OH).Activated halides ( Cl, I, Br ).
MyeloperoxidaseNitrous oxyde.
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Oxygen independent1. 1.Acids2. Lysozymes ( degrade bacterial
peptidoglycan)3. Lactoferrin ( Chelate iron ).4. Defensins and other cationic proteins ( damage membrane ).5. Proteases, Elastases and cathepsin G
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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
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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
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Extracellular bacteria the clearance will mostly depend on humoral protective immune response
Intracellular Bacteria their clearance will mostly decided by the cellular immune response
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Thank You