Vascular Changes , External manifestation of acute inflammation , CARDINAL SIGNS. Chemotaxis , Steps of Mechanism, features of acute and chronic inflammation Opsonization, Vascular and cellular events of acute inflammation , CHANGE IN VASCULAR FLOW AND CALIBER , OUTCOMES OF VASCULAR CHANGES , Phagocytosis , CHEMOTAXIS OFLEUKOCYTES ,OPSONINS , SEQUENTIAL STEPS of phagocytosis , Receptors, Engulfment, Killing and degeneration, Reactive Oxygen Species[ROS] , Reactive Nitrogen Species , Granules Enzymes & other proteins , Fate of Acute Inflammation

2. Topics to present
Vascular Changes
Chemotaxis
Opsonization
Phagocytosis

3. Definition
Inflammation is a response of
vascularized(vascular) tissues to
infections and tissue damage that
brings cells and molecules of host
defense from circulation to sites
where they are needed, to eliminate
the offending agents.
Note
 Inflammation is not harmful but it’s a
natural, protective response.
 But in some cases; excessive, defective or
misdirected inflammation results in
complexities.

4. External manifestation
The external manifestations of inflammation (acute) are called
CARDINAL SIGNS.
Heat
Pain
SwellingRedness
Loss of
function

5. Working Agents
Steps of Mechanism
I. Recognition of injurious
agent
II. Recruitment of Leukocytes
III. Removal of agents
IV. Response regulation(control)
V. Resolution[Repair]
CELLS
• MACROPHAGES, DENTRITIC CELLS, MAST CELLS, NEUTRO-PHILS etc.
• They secrete molecules( cytokines and other mediators)
MOLECULES
• PLASMA PROTEINS
• They also produce inflammatory mediators.

6. Types
There may be two types of inflammation:
1. Acute Inflammation (Initial, rapid response to
infections or tissue damage)
2. Chronic Inflammation (Prolonged response in which
tissue injury, inflammation and repair coexist in varying
form)

7. Events of Mechanism
Events
2_Cellular
Reactions
Chemotaxis
Opsonization
& Phagocytosis
1_Vascular
Reactions
Vascular
Changes

8. Vascular and cellular events of acute
inflammation

9. CHANGE IN VASCULAR FLOW
AND CALIBER
 VASODILATION is induced by
inflammatory mediators e.g.
histamine.
 Before vasodilation, there is a
transient Vasoconstriction.
 Former involves arterioles and
new capillary beds.
 It increases the blood flow at
inflammation site.
 This is the cause of Heat and
Redness[Erythema]

10. INCREASED VASCULAR PERMIBILITY
(VASCULAR LEAKAGE)
 Vasodilation is quickly followed
by INCREASED PERMIBILITY.
 RETRACTION OF ENDOTHELIAL
CELLS results in the opening of
inter-endothelial spaces which
increase permeability.
 ENDOTHELIAL INJURY results
endothelial necrosis which
further increase it.
 This leaks the fluid, plasma
proteins & leukocytes out.

11.  This escape from vascular
system to interstitium is
known as EXUDATION.
 Extracellular fluid may be:
 EXUDATE has high protein
content and cellular debris.
 TRANSUDATE has low
protein content, cellular
debris & specific gravity.

12. OUTCOMES OF VASCULAR CHANGES
ADVANTAGES
Maximize the movement of leukocytes from
circulation to the site of infection & injury.
Increased diameter,
Loss of fluid
Slow blood flow,
Conc. Of RBCs,
Increased viscosity
Stasis of blood
VASCULAR
CONGESTION,
ERYTHEMA

13. Definition
The locomotion of cells (leukocytes) along the chemical
gradient is called CHEMOTAXIS.
How Gradient forms?
It forms by both exogenous and endogenous
substances acting as CHEMOATTRACTANTS i.e.
Cytokines[chemokines & TNF]
Bacterial Products
Complementary system’s components(C5a)
Leukotriene B4 (LBT 4)
They are produced by microbes or host cells responding
injury or infection during immunological reactions.

14. Mechanism
 After exiting the circulation,
leukocytes reach the action site as,
 Chemo-attractants bind with the
receptor site at leukocyte.
 They roll(selectins), attach
firmly(integrins) on epithelium &
migrate through inter-epithelial
gaps.
 Signaling occurs calcium mobilizes,
assembly of cytoskeletal contractile
elements.
 At leading edge, actin polymerizes
& myosin localizes at back.
 By this leukocytes moves by
extending filopodia at back.

15. Fig. CHEMOTAXIS OF
LEUKOCYTES

16. Features
The nature of leukocytes infiltrate, in chemotaxis, varies
with:
I. Age of inflammatory response
II. Type of stimulus
e.g.(in most cases) during first 6-24 hours, Neutrophils
predominate & over 24-48 hours, monocyte-derived
macrophages dominate as inflammatory infiltrate.
Neutrophils plays great role as they are more in number,
respond to chemokines more rapidly & attach more firmly.
Former have less life span in tissues while macrophages
do proliferate.

17. Definition
The process of making
the microbe or damaged-
tissue cells more vulnerable
to phagocytes to engulf.
OR
An immunological
response to destroy
pathogens by immune
cells.

18. Definition
An antibody or specific
protein that binds to foreign
microbe or damaged cells to
make them more susceptible
to phagocytosis.
Example
• Immunoglobulin G [IgG]
• Complementary protein
C3b
• iC3b (cleavage product of
C3b)

19. Mechanism
Opsonins are attached
to the epitope.
Form a protein coating
around it.
Phagocytes bear cell
surface receptors for
these complements
fragments & express
high affinity for them.

20. Advantages
Help to perform phagocytosis
more readily & easily
Help in microbe recognition for
phagocytes

21. Definition
Phagocytosis is the
process of engulfing
the microbes or cellular
debris at site of
infection or injury.

22. Definition
Phagocytes are the cells
which perform phagocytosis.
Example
e.g.
 Neutrophils
 Macrophages

23. SEQUENTIAL STEPS

24. Mechanism
 Phagocytes have Mannose,
Scavenger & opsins’ receptors.
 Which recognize the chemical
substances just present in
microbial cell wall not that of
host.
 Opsonized microbial cell wall
enhanced phagocytic activity.

25. Receptors

26.  After binding receptors with
particles, cytoplasmic
extension(Pseudopodia) flow
around it.
 Plasma membrane pinches off
to form cytosolic vesicle
(Phagosome)
 Fusion of phagosome with
lysosome.
 Discharge of lysosomal contents.
 During this normal cells may
damage due to granular release.

27. Reactive Nitrogen
Species[ mainly
NO]
Lysosomal enzymes &
Granular enzymes
Reactive Oxygen
Species [ROS]
Elimination of dead cell debris and microbes.
Occurs in Lysosomes or Phagolysosomes.
Accomplished by three ways i.e.

28. Assembly & activation of a
multicomponent enzyme PHAGOCYTE
OXIDASE [ NADPH oxidase],oxidizes
NADPH.
Oxygen reduces to Superoxide anion.
This oxidation reaction , in neutrophils, is
tightly packed with phagocytosis known
as “RESPIRATORY BURST”.
Superoxide dismutate to Hydrogen
Peroxide but its not able to kill microbe
thus converted to HOCl by Superoxide
dismutase & Myeloperoxidase(MPO)
respectively.
Hydroxyl radical is also a powerful
destructive agent.
ROS are produced in phagolysosomes
where they ingest particles.

29. Nitric oxide (NO) is a soluble gas produced by arginine by
action of nitric oxide synthase (NOS)
There are 3 types of NOS:
iNOS kills microbes.
NO reacts with superoxide radical forming highly reactive free
radical Peroxynitrate.
Like ROS , NO highly reactive free radicals damage lipids
protein and nucleic acid of microbes of host cell.
Inducible
NOS
(iNOS)
Endothelial
NOS
(eNOS)
Neuronal NOS
(nNOS)

30. Neutrophils and monocytes have
granules packed with enzymes and
antimicrobial proteins.
They degrades microbes ,dead
tissues and may damage tissue.
There are 2 types of granules:
 Phagocytic vesicle fused with
lysosomal granules also engulf
materials.
1-Azurophil granule
(Primary) 2-Small Specific granule
(Secondary)

31. Fate of Acute Inflammation