1. INFLAMMATION
By
M. Wasif Zafar
Bpd01093-095
5th C
16th December 2011
2. Inflammation:
Definition:
Inflammation is a protective response intended to remove
injurious stimuli as well as the necrotic cells and tissues
resulting from original insert.
5. PROCESS OF INFLAMMATION:
Inflammatory Chemical
stimulus mediators
When the inflammatory Inflammatory response
stimulus is removed these (until
mediators are then injurious stimulus is
dissipated, catabolized or removed)
removed.
6. PLAYERS OF INFLAMMATION:
CIRCULATING CIRCULATING
CELLS PROTEINS
The inflammatory
responses have
many players.
They include
EXTRA
VASCULAR CELLULAR
WALL CELLS MATRIX
7. PLAYERS OF INFLAMMATION:
1. CIRCULATING CELLS:
Bone marrow derived polymorph nuclear leukocytes
e.g., Basophils, Esinophils and Neutrophils.
Lymphocytes
Monocytes
Platelets.
12. Acute Inflammation
“Inflammation, usually of sudden onset, marked by
the classical signs in which vascular and exudative
processes pre-dominate.”
Acute inflammation begins within seconds to
minutes following the injury of tissues. The damage
may be purely physical, or it may involve the
activation of an immune response.
13. Events in Acute Inflammation
Increased blood flow
Increased permeability
Migration of neutrophils
14. Increased Blood Flow and Edema
The first two of the above effects are readily visible
within a few minutes following a scratch that does
not break the skin. At first, the scratch is visible as a
pale red line. Then the surrounding few millimeters
of tissue on both sides of the scratch becomes red
as blood flow increases locally. Finally, the area
swells as additional fluid accumulates in the
interstitial spaces of the region, a condition known
as edema. The increased permeability of the
capillaries occurs because the endothelial cells
separate from one another at their edges.
15. Cell Adhesion Molecules
The first step is the binding of the neutrophils to the
endothelium of the blood vessels. The binding is due to
molecules, called cell adhesion molecules (CAMs),
found on the surfaces of neutrophils and on
endothelial cells in injured tissue.
The binding occurs in two steps.
In the first, adhesion molecules called selectins lightly
bind the neutrophil to the endothelium, so that it
begins rolling along the surface.
In a second step, a much tighter binding occurs
through the interaction of ICAMs on the endothelial
cells with integrins on the neutrophil.
17. Chemotaxis
Once outside the blood vessel, a neutrophil is
guided towards an infection by various diffusing
chemotactic factors. Examples include the
chemokines and the complement peptide
C5a, which is released when the complement
system is activated either via specific immunity or
innate immunity.
18. Eosinophils
In some circumstances eosinophils rather than
neutrophils predominate in acute inflammation.
This tends to occur with parasitic worms, against
which neutrophils have little success, or with a
response involving the antibody IgE. Eosinophils
release several proteins, such as major basic
protein, which are often effective against parasites.
Eosinophils also release several regulatory
molecules that increase endothelial permeability.
19. Inflammatory Paracrines
What causes the characteristic sequence of events in acute inflammation?
Various cells at the site of tissue damage or of a specific immune
response release regulatory molecules that act locally as paracrines.
Macrophages and lymphocytes are important sources of inflammatory
paracrines; macrophages release IL-1 and TNF-alpha, which have
powerful widespread effects.
Also important are mast cells, which are found throughout the
body, especially under epithelia. Mast cells are filled with large vesicles
containing histamine and other inflammatory paracrines (They also
release PG D2, several LTs and TNF-alpha, described below). Factors
associated with tissue damage can trigger the exocytosis. But
sometimes it is a specific immune response that triggers the release of
the inflammatory paracrines.
20. Inflammatory Paracrines
Also, various arachidonic acid derivatives are
important. Both prostaglandins (notably PG D2) and
leukotrienes (LT) can be important, depending on
the tissue.
Complement peptides, C3a and C5a
Various other molecules including nitric
oxide, certain platelet products, kinins, and
serotonin, etc
21. CHRONIC INFLAMMATION:
Chronic inflammation is the inflammation with
prolonged duration usually from weeks to months
and sometimes to years in which active
inflammation, tissue injury and healing process
proceed simultaneously.
23. ORIGIN AND PROCESS:
Chronic inflammation arises from acute
inflammation. This transition takes place if the acute
responses cannot be resolved either because of the
persistence e.g., of injurious stimuli or by
interference of the normal healing process
e.g., peptic ulcer.
Some types of injuries engender responses with
chronic inflammation initially e.g., viral infections.
26. CHRONIC INFLAMMATORY CELLS & MEDIATORS:
1) MACROPHAGES:
Macrophages are white blood cells within tissues, produced by
the division of monocytes.
A majority of macrophages are stationed at strategic points
where microbial invasion or accumulation of dust is likely to
occur. Each type of macrophage, determined by its
location, has a specific name:
In liver Kupffer cells
Spleen and lymph nodes Sinus histocytes
Nervous system Microglial cells
Lungs Alveolar macrophages
28. CHRONIC INFLAMMATORY CELLS & MEDIATORS:
When macrophages become activated they produce different type of
biologically active substances that either cause one of
• Cell injury
• Fibrosis.
31. CHRONIC INFLAMMATORY CELLS & MEDIATORS:
2) LYMPHOCYTES:
Both T- & B-lymphocytes are involved in chronic
inflammation. Their migration is brought about by
specific adhesion molecules and cytokines. The T-
lymphocytes work in reciprocal with B-lymphocytes
in chronic inflammation. The already activated
macrophages release TNF & IL1 and activate the
inactive lymphocytes which then produce different
antibodies that cause destruction of antigens at the
inflammatory site.
32. CHRONIC INFLAMMATORY CELLS & MEDIATORS:
3) ESINOPHILS:
They are usually found in parasitic infections and IgE
mediated allergic reactions. Their migration is
brought about by adhesion molecules produced by
leukocytes and epithelial cells. Esinophils specific
granules contain Major Basic Proteins which is
highly cationic &toxic for parasites.
33. CHRONIC INFLAMMATORY CELLS & MEDIATORS:
4) MAST CELLS:
Mast cells are tissue cells which are like basophils in
shape. They are present in bone marrow and
around blood vessels and do not enter the blood.
They are specifically armed with IgE antibodies
against certain antigens. When these antigens are
encountered, they release histamines and amino
acid metabolites. They cause initial vascular changes
in acute inflammation and also cause anaphylactic
reactions.
35. TYPES OF CHRONIC INFLAMMATION:
1) GRANULOMATOUS INFLAMMATION:
Characterized by aggregates of activated
macrophages that assume a squamous cell like
epithelloid appearance.
GRANULOMA is defined as aggregates of
macrophages formed due persistant response of T-
lymphocytes to particular antigens.
This has a granular cheesy appearance called as
caseous necrosis.
