INFLAMMATION

(RADANG)
Introduction
In-flame to set fire. (red, hot, pain)
Inflammation is dynamic response
of vascularised tissue to injury.
It is physiologic, protective response.
Serves to bring defense & healing
mechanisms to the site of injury.
INFLAMMATION
Tissue and cell involvement in inflammatory
event
Inflammation Causes: ..Injury
Physical agents Trauma, radiation,
Infection microbial agents
Chemicals acid, alkali, toxins
Ischemia / Infarction lack of blood..
Immune reaction
Appearance of Inflammation:

Flush: Red spot -
capillary dilatation.
Flare : Red area -
arteriolar dilatation.
Weal : Swelling -
exudation, edema.
Lewis Triple Response: - old!
Cardinal Signs of
Inflammation
Calor : Warm Hyperaemia.
Rubor : Redness Hyperaemia.
Dolor : Pain Nerve, Chemical med.
Tumor : Swelling Exudation
Functio laesa: Loss of function (Virchow 1902)
Celsus, 30 BC - Latin
Calor, Rubor, Dolor, Tumor, Loss of
function.
Surgical wound inflammation:
Calor, Rubor, Dolor, Tumor, Loss of function.
Inflammation - Mechanism
1. Vaso dilatation

2. Exudation - Edema

3. Emigration of cells

4. Chemotaxis

5. Phagocytosis
Mechanisms of
increased
vascular
permeability in
inflammation
Intravascular bloodflow
Mechanism of Inflammation:
Sequence of leucocytic events in
inflammation
Emigration of Leucocytes
Mechanism of
phagocytosis
Mouth Aphthus ulcer
Calor, Rubor, Dolor, Tumor, Loss of function.
Laryngitis:
Calor, Rubor, Dolor, Tumor, Loss of function.
Acute Enteritis:
Calor, Rubor, Dolor, Tumor, Loss of function.
Pneumonia
Inflammation of
lung
Calor, Rubor, Dolor, Tumor, Loss of
function..!
Neutrophil Margination
Lung Normal / Pneumonia
Pneumonia - Exudation
Normal - Meningitis
Heat Redness Swelling Pain Loss Of Func.
The 5 Cardinal Signs of
Chemical Mediators of
Inflammation:
Cellular hormones cytokines.
Released by cells act on same or nearby cells
Each phase of Inflammation is orchestrated
by several chemical mediators cytokines.
Modifying these modifies inflammation
drugs
Endogenous & Exogenous.
Locally produced & Plasma factors.
Chemical Mediators of
Inflammation:
Locally produced
Histamine
Seratonin/5HT
Interleukins.
Prostaglandins*
Leukotrienes*
Plasma derived
Kinins
Complements
Coagulation
system
Plasminolysis
system
Others: H2O2, NO,
O2*rad.
Chemical Mediators of
Inflammation:
Vasodilatation: Histamine, Pgs, Nitric oxide
BV permeability: Hist, bradykinin, C5a, LB4
Leukocyte adhes: IL8, LB4, C5a, TNF
Chemotaxis: LB4, IL8, bacterial toxins, C3, C5.
Pain: Prostaglandins & Bradykinin.
Pengaruh mediator kimia
Vasodilatasi
histamin, bradikinin, prostaglandin
Permeabilitas kapiler
histamin, bradikinin, C3a, C5a, lekotrin, PAF
Kemotaksis
C5a, lekotrin, produk kuman, cytokine
Marginasi lekosit
C4a, lekotrin
Demam
Prostaglandin, pirogen endogen
Rasa sakit
Bradikinin, prostaglandin
Chemical Mediators of
Inflammation:
Vasoactive amines - Histamine, Seratonin
vaso dil.
Complement system C1-9 cytolysis, opsonins.
Kinin System Kallikreins Bradykinin
Clotting system FXII, FX, Fibrin, Plasmin
Arachidonic acid metabolites:
Prostaglandins - (cyclooxigenase) - Pyretic
Leukotrienes (Lipoxigenase) -
Lipoxins anti-inflammatory action also.
Others:
H
2
O
2
, Nitric Oxide, Lysozymes,O2 free radicals
Chemical mediators in inflam.
MEDIATOR OF ACUTE
INFLAMMATION
MEDIATOR VASODILATATION INCREASED PERMEABILITY CHEMOTAXIS OPSONIN PAIN
---------------------------------------------
IMMEDIATE SUSTAINED
--------------------------------------------------------------------------------------------------------------------------------------------------------------
HISTAMINE + +++ _ _ _ _

SEROTONIN(5-HT) + + _ _ _ _

BRADYKININ + + _ _ _ +++

COMPLEMENT 3a _ + _ _ _ _
COMPLEMENT 3b _ _ _ _ +++ _
COMPLEMENT 5a _ ++ _ +++ _ _

PROSTAGLANDINS +++ +++ + ? +++ _ ++
LEUKOTRIENES _ +++ + ? +++ _ _

LYSOSOMAL
PROTEASES _ _ ++ _ _ _

OXYGEN RADICALS _ _ ++ _ _ _
--------------------------------------------------------------------------------------------------------------------------------------------------------------
Arachidonic Acid
Leukotrienes
LTC4, D4, E4
Cyclooxygenase
5-Lipoxygenase
Prostaglandins
Prostacyclins
Cell Damage
Cell Membrane
Phospholipids
5-LO inhibitors
Steroids
NSAID
Types of Inflammation:
Time:
Acute & Chronic
Predominant process:
Suppurative neutrophils - bacterial
Fibrinous - fibrin - immune
Serous fluid - viral
Granulomatous chronic
TB/fungus/Foreign body.
Eosinophilic parasite, immune.
Granuloma, chronic inflammation
ex. TBC
Central necrosis
Epitheloid cells
Langhans type
giant cells
Lymphocytes
Acute upto days.
Vascular changes : Hyperemia &
exudation.
PMNs Neutrophils, Pus/suppuration.
Chronic - Weeks to Months or Years
No Vascular changes.
Fibrosis Scarring.
MNs - Lymphocytes and macrophages
Inflammation Types
Inflammation Outcome
Chronic
Inflammation
Abscess
Sinus Fistula Ulcer
Acute
Inflammation
Healing
Injur
y
THE IMMUNE RESPONSES AGAINST
INFECTION :
UNIQUE INTERACTION BETWEEN HOST AND
PATHOGENS
PROTECTIVE FUNCTIONS OF THE IMMUNE
SYSTEM
NON PATHOGENS - INERT ANTIGEN /
IMMUNOGEN
PATHOGENS - VIRUS
- BACTERIA
- PARASIT
- FUNGI
IMMUNOGENICITY / ANTIGENICITY
SURFACE STRUCTURES OF PATHOGENS
BACTERIA
Gram-positive
Gram-negative
Mycrobacteria
Spirochaete
VIRUSES
Viral proteins
(virion, infected cell membrane)
PARASIT
Surface membrane
Excretory - Secretory (ES Ag)
MECHANISMS OF IMMUNITY
The first line of defence :
Independent on antigen recognition
- barriers (physical, chemicals, mechanical)
- complement, cytokines (TNF, IL-1)
- cells :phagocytes (mononuclear, polymorphonuclear)
NK cells
The second line of defence :
Dependent on antigen recognition
- humoral : antibodies
- cell-mediated : T cells, M
- combination : ADCC
BACTERIAL INFECTIONS : A model for studies
Immunopathogenicity
Natural responses
Against LPS
Complement activation
Phagocytic activity
Adaptive responses
Antibody response
T-cell response
MECHANISMS OF IMMUNOPATHOGENICITY
Toxicity without invasiveness
Invasiveness without toxicity
Ab response
cell-mediated response
Both activities
Ab & cell responses


MECHANISM OF ACTION OF LPS (lipopolysaccharide)
MICROBICIDAL EFFECTS OF PHAGOCYTIC
CELLS
Oxygen - dependent
Oxygen - independent
ROI
RNI
Cathionic protein
Acidification of pH
Lactoferrin, lysozyme
Ab responses
bacterial toxin neutralization IgG, IgM
against attachment
Ab to fimbriae, lipoteichoic acid, some
capsules : IgG, IgM, SIgA
trigger C-mediated lysis
opsonization via Fc and C
3
receptors
neutralize spreading factors, enzymes
(e.g. hyaluronidase)
T cell responses
Tc (CTL) - intracellular pathogens
Against superantigens (staphylococcus, streptococcus,
mycoplasmas)
e.g. T cells / CD
8
+

binds directly to V of Ag receptors
no processing and presentation
Massive cytokine / lymphokine release
Toxic shock syndrome
Ag
EVADE MECHANISMS AGAINST PHAGOCYTE-
MEDIATED KILLING
secret repellents / toxins inhibit chemotaxis
bear capsules / outer coats inhibit attachment
releases molecules (M. tuberculosis) interfere
phagolysosome fusion
secret catalase break down hydrogen peroxide
possess a phenolic glycolipid (M.leprae) scavenges
free radicals
release lipoarabinomannan (Mycobacteria) block
the ability of M in respond to IFN- stimulus
others : anatomic sequestration, antigenic mimicry,
antigenic variation (parasites)
EXCESSIVE RELEASE OF CYTOKINES
CONCLUSION
The immunity to pathogenic agents is primarily
conducted by natural immune responses, and
working in concert with adaptive responses
The successful of pathogens invade to and persist
in the body is pretty much depending on the status
of immunity, the virulence factors of the agents and
their smart evade mechanisms against effector
function of the immune system