Transcript 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
1. Genetically different.
2. Bacteria contain many structurally non-self
substances.
3. Bacteria produce many antigenic products
Bacterial components are
excellent activator of Innate
Antigen-Non Specific immune
response
Direct Activators
Lipopolysaccharide (Endotoxin)
Lipoarabinomannan.
Lipoteichoic acid
Glycolipids and Glycopeptide.
Polyanions
N-formyl peptides
Act as Chemotactants
Peptidoglycans fragments
Cell Surface activation of alternating pathway of
the complement ( C3a and C5a )
Activation of Antibacterial immune Response
Peptidoglycan layer of Gram (+) bacteria and
Lipopolysaccharides layer of Gram (-) bacteria
1. 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
Lipopolysaccharide – LPS / Endotoxin
is a strong activator of :
Macrophage
B Cells
Others ( endothelials cells)
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.
Activation of complement cascade by Gram
(+)/Gram (-) Bacteria provide the following
protective immune responses
1. 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)
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
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
Phagocyte and Phagocytosis
The first cells to appear in acute infection :
1. 1.Polymorphonuclear Neutrophils (PMN)
2. 2.Monocyte
3. 3. Eosinophyl ( Occasionally )
Followed later by Macrophage
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”
Phagocytosis of Bacteria by
Macrophage and Neutrophils
involved several process
1. Attachment.
2. Internalization.
3. Digestion
Attachment
1. 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.
Internalization
After the attachment, the bacteria
will be surrounded by a portion of
plasma membrane and formation of
phagocytic vacuole that surrounding
the bacteria
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
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)
Oxygen dependent
Hydrogen peroxidase (NADPH Oxydase and
NADH oxydase.
Superoxydase.
Hydroxyl radicals (OH).
Activated halides ( Cl, I, Br ).
Myeloperoxidase
Nitrous oxyde.
Oxygen independent
1. 1.Acids
2. Lysozymes ( degrade bacterial
peptidoglycan)
3. Lactoferrin ( Chelate iron ).
4. Defensins and other cationic proteins
( damage membrane ).
5. Proteases, Elastases and cathepsin G
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
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
Extracellular bacteria the clearance
will mostly depend on humoral
protective immune response
Intracellular Bacteria their
clearance will mostly decided by
the cellular immune response
Thank You