This document provides an overview of inflammation. It begins by defining inflammation as the body's response to tissue injury and infection, describing the five classical symptoms. The inflammatory process is then summarized in three steps: 1) vasodilation which increases blood flow, 2) leukocyte emigration from blood vessels, and 3) phagocytosis where pathogens are engulfed and digested. Key players in inflammation that are discussed include histamine, serotonin, bradykinins, arachidonic acid metabolites, complements, and reactive oxygen intermediates. The document notes that while inflammation is beneficial for fighting pathogens, it can also cause collateral host tissue damage.

1. INFLAMMATION
Created by,
Sam Aaseer Thamby
Lecturer, Faculty of Pharmacy
AIMST University
Malaysia

3. INTRODUCTION
 First described by Cornelius Celsus 2000 years ago.
 It is an important non-specific defensive reaction to tissue injury (by
pathogen invasion or wound injury etc.)
 It is the response by which the body not only destroys the invading
pathogens, but also the healthy cells (in the host)
 E.g., Anaphylaxis and RA are due to uncontrolled inflammatory
response.
 Caused by various agents like pathogen infection, burns, physical
injury, chemical injury (acid or alkalies).
 Triggered by a complex set of events induced by pathogen invasion or
tissue injury
 Ruptured cells in infected areas release their cytoplasmic contents
 Increased acidity in the surrounding ECF (↓ed pH)

4.  These changes lead to the 5 Classical Symptoms of Inflammation:
• Rubor (Redness due to vasodilation and hyperemia)
• Calor (Heat; area becomes hot due to excessive blood flow)
• Dolor (Pain due to bradykinins and PGs at the inflamed site)
• Tumor (Swelling due to excess fluid at the site)
• Functio Laesa (loss / reduction of body functions)
THE INFLAMMATORY PROCESS (briefly)
 Breach in the skin ; Bacteria (pathogens) invade the body
 I – VASODILATION ( capillaries enlarged; blood vessels’ diameter
enlarged, causing increased volume of blood flow with decreased
velocity; microcirculation is affected)
 II – Circulation slows down; Margination (blood cells mostly WBCs
adhere to the vascular endothelium); Emigration (neutrophils get out
of the capillaries and enter the inflamed site)
• First 24 hrs – neutrophils are the most predominant;

5. • Later, monocytes also are present;
 III – PHAGOCYTOSIS ( pathogen is engulfed and degraded or digested
within the phagocyte)
• Removal of the necrotic or damaged tissue as well as infective
organisms.
• Large nos. of WBCs also die (the fluid in inflamed site becomes white
and is the main component of Pus)
• Host (our body) cell damage occurs by the inflammatory process.
LOCAL VASODILATATION
• Due to histamine (H1) and serotonin (5HT) release. H1 from the mast
cells and basophils; serotonin from platelets.
• H1 relaxes arteriolar and venular smooth muscles →vasodilatation;
• Vasodilation → increased vol. of blood flow with decreased velocity;
increased capillary permeability → emigration of WBCs

6. LEUCOCYTE EMIGRATION
• Normally, most WBCs and RBCs occupy the central axis of
flowing blood in a blood vessel.
• If the flow velocity is ↓ed, the WBCs and RBCs occupy the
periphery of the flow and would come very close to the vessel
walls (MARGINATION)
• Post-Margination: WBCs stick to the capillary walls (by C5a and
AAMs)
• WBCs emigrate (neutrophils go first and release Chemotactic
factor, which draws out the monocytes); later RBCs also
emigrate
• The emigrated WBCs are drawn towards the invading pathogen
(+ Chemotaxis)
WHAT IS CHEMOTAXIS?????

8. PATHOGEN DIGESTION
• Metabolic activity within the neutrophils → H2O2 forms in
the neutrophils → H2O2 + MPO in the ‘azurophilic granules’
kill the pathogen. (MPO increases the lethal activity of
H2O2)
• MPO = Myeloperoxidase
• Azurophilic granules (1° granules): are lysosomal granules
located within the neutrophils; they contain proteo or amylo-
lytic granules + MPO granules + lysozyme enyme granules
• Metabolic activity within the neutrophils also ↑es the lactic
acid levels in the neutrophil → fall in intracellular pH of
neutrophil and death of the ingested pathogen

10. • Monocytes don’t have MPO. So, monocytes have to kill the
pathogen with H2O2 only.
• Sometimes, the defense mechanisms of the human body
aren’t strong enough as the pathogens are stronger →
infection and inflammation spreads rapidly
• During phagocytosis and pathogen digestion, some
destructive agents like ROIs are released from the
neutrophils → damage and destruction of the host cells.
• After inflammation, the process of repair is initiated (Wound
Healing)

11. HOW DO PATHOGENS SURVIVE???
• M.tuberculosis, M.leprae, L.pneumophila, T.gondii: inhibit
phagosome fusion with lysosomes, preventing exposure to
toxic lysosomal contents
• Trypanosoma cruzi, Listeria monocytogenes, Shigella
flexneri: lyse phagosomal membrane and escape into the
cytoplasm
• Leishmania spp., M.lepramurium, S.typhimurium: resist
inactivation by lysosomal factors
• Coxiella spp.: reproduce inside the phagolysosome

12. BRADYKININS
• Vasoactive amine involved in vasodilatation
• Factor XII (Hageman factor) [present normally in plasma]
• Active Factor XII (β XIIa)
• βXIIa + prekallikrein Kallikrein
• Kallikrein + HMW Kininogen BRADYKININ
COMPLEMENTS
• Proteins by nature; Produced by the liver
• C1, C2, C3 on activation form C1a, C2a, C3a
• Roles: Helps in ….
• Neutrophil (or monocyte)-mediated immunity against the
pathogens (Non-specific immunity)
• Phagocytosis; ↑ing capillary permeability; chemotaxis; Ag-Ab
reaction in lymphocyte-mediated immunity

13. ARACHIDONIC ACID METABOLITES (AAMs)
• Arachidonic acid + polyunsaturared fatty acids
• Belong to the class Eicosanoids
• Can’t be synthesized in the body (essential fatty acids)
• E.g., Classical PGs (PGF2 , PGE2 etc..)
• TXs (TXA2)
• Prostacyclins (PGI2)
• Leukotrienes (LTS) Lipo Oxygenase (LOX)pathway
• PGF2 , PGE2 are powerful vasodilators (local vasodialatation
in inflammation)
• TXA2 is a vasoconstrictor causing platelet aggregation
(hemostasis)
• PGI2 opposes vasoconstriction
Cyclo
Oxygenase
(COX)
PATHWAY

14. FOR YOUR INFO….

15. • Chemotaxis: the cellular movement of WBCs initiated by
chemokines; may be mediated by exogenous (bacterial
products) or endogenous chemoattractants (cytokines;
complement systems; LOX pathway products)
• Chemokines: are a family of small cytokines that induce
chemotaxis.
• Cytokines: are cell signalling molecules that aid cell to cell
communication in immune responses and stimulate the
movement of cells towards sites of inflammation, infection
and trauma.
• Chemotactic agents (CA): also called chemoattractants; e.g.,
C5a, Platelet Factor (PF4); They combine with the receptors on
WBCs; cause + Chemotaxis
• Marginal Pool: Even in the absence of inflammation, some
WBCs marginate. They constitute the Margin Pool
• AAMs: Arachidonic Acid Metabolites; aka Eicosanoids; e.g.,
PGs, Leukotrienes (LTs), Thromboxane (TX), Prostacyclins

16. • Receptor + CA → ↑ed Ca2+ entry into the cells → ↑ed
contraction within the WBCs → ↑ed WBCs locomotion toward
the pathogen → Invasion of the pathogen; Phagocytosis
and digestion of the pathogen.

17. • Complement: Substance normally present in serum; it
combines with Ag-Ab complex to destroy the pathogens
• Bradykinin: Is a peptide formed from protein degradation by
enzymes; is a powerful vasodilator;
• PGs: Hormones produced in many body tissues (brain,
lungs, uterus etc..)
• Reactive Oxygen Intermediates (ROIs): Macrophage
lysosomes contain oxygen-dependent enzymes that produce
ROIs like superoxide radical, H2O2 singlet oxygen and
hypohalite ions. These ROIs are toxic products that cause
damage to the normal cells of the host tissue.
• Prekallikrein: It is cleaved by β XIIa to form plasma
kallikrein.
• Kallikrein: serine protease that activates kinins
• HMW Kininogen: is a circulating plasma protein that is
involved in the initiation of blood coagulation.

18. TO BE CONTINUED …