Professional Documents
Culture Documents
Presented by
K.V.Chalapathi
I MDS
Department of Oral and Maxillofacial Pathology
Vishnu Dental College
Inflammation
Etymology : latin inflammare meaning to set
afire.
Inflammation is an injurious stimuli causing a
protective vascular connective tissue reaction.
Injury can be due to any agent.
It is a body defense reaction in order to
eliminate or limit the spread of the injurious
agent as well as to remove a consequent
necrosed cells and tissues.
Cellular Injury
Acute Inflammation
Healing
Chronic Inflammation
Healing
Granuloma formation
Healing
Agents causing
Inflammation
Physical agents
Infective agents
Chemical agents
Immunological agents.
Historical Highlights
Inflammation was first described in an
Classification
According to the duration:
Acute Chronic (+ subacute, hyperacute)
fibrous tissue)
majority
Specific (e.g. TB)
Acute inflammation
Acute inflammation is a rapid response to an
site.
Intravascular activation of platelets.
PMNs as inflammatory cells.
Chronic Inflammation
Chronic inflammation is considered to be
ACUTE INFLAMMATION
Acute inflammation is a rapid host
Hemodynamic changes
Vascular leakage
Five mechanisms are known to cause the
vascular leakiness.
Histamines, Bradykinins, Leukotrienes : cause an
dependentvasodilator, increases
vascularpermeability, causes dilation of nonvascularsmooth muscle.
Leukotriene B4may play a pivotal role in the
induction of neutrophil-endothelial cell
adherence. Leukotriene B4-induced endothelial
cell hyperadhesiveness for neutrophils depends
on increased CD11/CD18 expression on the
neutrophil surface and possibly a specific domain
of the adhesion molecule CD54 found on
endothelial cells
Bradykinin triggers the production of other
Cellular Events
The processes involving leukocytes in
tissues.
Recognition of microbes and necrotic tissues.
Removal of the offending agents.
to interstitial tissue
extravassation.
transmigration
Emigration of:
Chemotaxis
Adhesion
adhesion.
Other sets of adhesion molecules participate,
such as the integrins.
Ordinarily down-regulated or in an inactive
conformation.
Diapedesis
Transmigration across
Endothelium
Chemotaxis
Chemotaxis: A reaction by which the direction of
Chemotaxis
injury (chemotaxis)
Soluble bacterial products
Complement components (C5a)
Cytokines (chemokine family e.g., IL-8)
LTB4 (AA metabolite)
the signals
Various receptors
Receptors for the microbial products: TLRs
These are present on the cell surface and in the
G protein-coupled receptors:
Found on neutrophils, macrophages and other
Receptors cntd
Receptors for opsonins:
Leukocytes express receptors for proteins that
coat the microbe. This process of coating for
ingestion is called as opsonisation and
substances are opsonins. The substances
include antibodies, complement proteins and
lectins
Receptors for cytokines:
Interferon secreted by natural killer cells. It is
Phagocytosis
It involves 3 sequential steps
Recognition and attachment of the particle to
be ingested by the leukocyte.
phagocytic vacuole.
Oxidative Burst
Reactive oxygen species formed through
phagolysosome.
Hydrogen peroxide broken down to water and
oxygen by catalase.
Dead microorganisms degraded by lysosomal
acid hydrolases.
emphysema)
Eg.:
Acute ARDS, Asthma, Glomerulonephritis, Septic
shock, Vasculitis.
Chronic Arthritis, Asthma, Atherosclerosis, Chronic
lun disease.
Chemical Mediators
Leukotrines, Lipoxins.
Platelet-aggrevating factor (PAF).
Reactive Oxygen Species.
Nitric Oxide.
Cytokines and Chemokines.
Neuropeptides.
Vasoactive Amines
Histamines :
Stored as preformed molecules in cells.
First mediators to be released during inflammation.
Richest source of histamine are Mast cells.
Also in basophils and platelets.
Histamine is released by mast cell degranulation in
response to various stimuli, including physical
trauma; binding of antibodies to mast cells which
underlies allergic reactions; fragments of
complement called anaphylotoxins (C3a,C5a);
histamine releasing proteins derived from
leukocytes; neuropeptides (e.g., substance P); and
cytokines (IL-1, IL-8).
Histamines cntd..
Action
Vaodilatation.
Increased vascular permeability thus
interendothelial gaps in vennules.
Microvascular endothelial cells activation.
Serotonin (5-hydroxytryptamine)
Source is platelets.
Actions similar to histamine.
Release of serotonin from platelets is
endothelial cells.
It increases the activity of synthesis of other
mediators, particularly eicosanoids, by leukocytes.
It causes
Platelet aggregation
Vasodilatation
Increased vascular permeability
Leukocyte adhesion
Chemotaxis
Degranulation
Oxidative burst
Nitric Oxide
These are alo known as endothelium-derived
relaxing factor.
It is produced by endothelium, macrophages,
and some neurons in brain.
NO is synthesized from L-arginine by an enzyme
nitric oxide synthetase (NOS).
It has a dual role in inflammation :
Relaxes the smooth muscle and promotes
In Chronic Inflammation
Chemokines
These are the family of small proteins (8-10kD)
Chemokines
C-X-C chemokines :
Have one amino acid residue separating two conserved
cysteine residues.
They act primarily on neutrophils.
Secreted by activated macrophages, endothelial cells and
causes activation and chemotaxis of neutrophils.
Inducers are microbial products and other cytokines mainly IL1, TNF.
C-C chemokines :
Have the first two conserved residues adjacent.
They act by monocyte chemoattractant protein (MCP-1),
Chemokines
C chemokines :
They lack two ( the first and third) of the four conserved
cysteines.
They act on lymphocytes by lymphotactin.
CX3C chemokines :
These contain three amino acids between two cysteines.
The only known member of this family is fractalkine.
They exists in two forms cell surface bound proteins that
Neuropeptides
These are secreted by sensory nerves and
Complement system
In acute inflammation
Vasodilation, vascular permeability, mast cell
degranulation (C3a, C5a)
Leukocyte chemotaxin, increases integrin avidity (C5a)
As an opsonin, increases phagocytosis (C3b, C3bi)
Kinin system
Clotting System
Cascade of plasma proteases
Hageman factor (factor XII)
Collagen, basement membrane, activated
platelets converts XII to XIIa (active form)
Ultimately converts soluble fibrinogen to
insoluble fibrin clot
Factor XIIa simultaneously activates the
brakes through the fibrinolytic system to
prevent continuous clot propagation
Endothelial activation, leukocyte recruitment
Outcomes of Acute
Inflammation
Complete resolution
little tissue damage
capable of regeneration
Scarring (fibrosis)
in tissues unable to regenerate
excessive fibrin deposition organized into fibrous
tissue
or fungal infections
Progression to chronic inflammation (next)
Outcome of inflammation
Fibrosis / Scar
Resolution
Injur
y
Acute
Inflammation
Chronic
Inflammation
Fungal
Viral
TB etc
Abscess
Ulcer
Sinus
Fistula
Chronic Inflammation
Chronic inflammation is inflammation of
Morphologic features
Infiltration with mononuclear cells, which
Mononuclear/Phagocyte System
Macrophages
scattered all over (microglia, Kupffer cells,
sinus histiocytes, alveolar macrophages)
circulate as monocytes and reach site of injury
within 24 48 hrs and transform
become activated by T cell-derived cytokines,
endotoxins, and other products of inflammation.
T and B Lymphocytes
Antigen-activated (via macrophages and
dendritic cells).
Release macrophage-activating cytokines (in
turn, macrophages release lymphocyteactivating cytokines until inflammatory
stimulus is removed).
Plasma Cells
Terminally differentiated B cells.
Produce antibodies.
Eosinophils
Found especially at sites of parasitic infection,
Granulomatous inflammation
Distinctive chronic inflammation type.
Cell mediated immune reaction (delayed).
Macrophage is the major player
Granuloma is a focal area of inflammation made
Granulomatous inflammation
1. Bacteria
TBC
leprosy
syphilis (3rd stage)
2. Parasites + Fungi
3. Inorganic metals or dust
silicosis
berylliosis
4. Foreign body
suture (Schloffer tumor), breast prosthesis
5. Unknown - sarcoidosis
Systemic effects
Fever
One of the easily recognized cytokinemediated(esp.IL-1, IL-6, TNF) acute-phase
reactions including
Anorexia
Skeletal muscle protein degradation
Hypotension
Leukocytosis
Elevated white blood cell count
Bacterial infection (neutrophilia)
Parasitic infection (eosinophilia)
Viral infection (lymphocytosis)
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