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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

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.

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

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

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

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