8.

1 Sequence of Inflammatory
Events and their role in the
Initial Response to Invasion

 Antigens are normally

introduced into the body
across the mucosa or the
epithelia.
Acute inflammatory
response is often the first
response to the invasion.

1.Activation of vascular
endothelium in breached
epithelieal layer.
2.Cytokines and other
inflammatory mediators are
released in the area as a result
of tissue damage.
3.Included are the expression of
selection-type adhesion
molecules on endothelial cells.

4. Neutrophils are the first cells

to bind to the inflamed
epithelium and extravasate
into the tissues, peaking at 6
hours.
5. Monocytes, macrophages, and
eosinophils may arrive 5 6
hours later in response to
neutrophil-released mediators.

 Remaining inaccessible to the

8.2 Role of Microbia
host immune system
Varying or shedding antigen
Resisting innate immune
defenses
Preventing T cell activation or
impairing effective T cell
antimicrobial responses by
specific or non-specific
immunosuppression

9.1 Mechanism and

Chemoattractive Molecules involved
in phagocytic extravasation

 Extravasation of
phagocytes in the area
requires four sequential
steps:
Rolling
Activation of
chemoattractants
Arrest and adhesion
Transendothelial migration

 Rolling
Phagocytes attach loosely to
endothelium by low-density selection
carbohydrate interactions
E-selection molecules on the
endothelium bind to mucin-like
adhesion molecules on the phagocyte
membrane
Because of blood flow, detachment and
reattachment occurs, rolling phagocyte
along endothelial surface until stronger
binding forces can be elicited

 Activation of
Chemoattractants
Chemokines released in
the area (e.g. IL-9)
complement split product
C5a and N-formyl peptides
produced by bacteria, bind
to receptors on phagocyte
surface and trigger a Gprotein mediated activated

 Activation of
Chemoattractants
Signal causes
conformational change in
integrin molecules in the
phagocyte membrane that
increases their affinity for
Ig-superfamily adhesion
molecules on the
endothelium

 Arrest and adhesion

Interaction between
integrin and Ig-superfamily
cellular adhesion
molecules (Ig-CAMS)
stabilizes adhesion of the
phagocyte to the
endothelial cells.

 Transendothelial
migration
Phagocyte extends
pseudopodia through the
vessel wall and
extravasates into the
tissues

Chemoattractiv Origin
e Molecules
Chemokines (IL-8) Tissue, mast cells,
platelets,
neutrophils,
monocytes,
macrophages,
eosinophils,
basophils,
lymphocytes
Complement split Endothelial
product C5a
damage
activation

Chemoattract Origin
ive Molecules
Fibrinopeptides Endothelial damage
activation Hageman
factor thrombin fibrin
clot degradation
Leukotriene B4 Membrane phospholipids
of macrophages,
monocytes, neutrophils,
mast cells arachidonic
acid cascade
lipoxygenase pathway
FormylReleased from
methionyl
microorganisms