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INFLAMMATION
Enflammare
Set a fire
Presented by
Anusha Vaddi
MDS
Narayana dental college
1. INTRODUCTION
2. HISTORY
3. CAUSES
4. CARDINAL SIGNS
5. TYPES OF INFLAMMATION
6. ACUTE INFLAMMATION
VASCULAR EVENTS
CELLULAR EVENTS
7. CHEMICAL MEDIATORS
8. MORPHOLOGICAL PATTERNS OF
ACUTE INFLAMMATION
9. CHRONIC INFLAMMATION
10. SYSTEMIC EFFECTS OF
INFLAMMATION
11.REGULATORS OF INFLAMMATION
12. FACTORS DETERMINIG VARIATIONS
IN RESPONSE
Introduction
Defined as
“Local response of living tissues to injury due
to any agent”
 Fundamentally protective response
 Ultimate goal is to get rid of intial cause cell
injury(microbes, toxins)
 Consequence of such injury(necrosis, tissues)
 without inflammation wounds go unchecked, never
heal
HISTORICAL HIGHLIGHTS
3000B.C Egyptians first described
1st century Celsus described cardinal signs
1793 John hunter inflammation not
disease, non specific response
that has salutary effect on host
1839 Conheihm used microscope to
observe changes in vessels
1880 Metchinkoff discovered phagocytosis
Paul ehrlich proposed humoral theory
of immunity
1908 Both got nobel prize
1924 Lewis explained role of chemical
mediators in inflammation
Pioneers of inflammation
EVOLUTION OF INFLAMMATION
Sponges , coelenterates body cavity is filled
with coelum, cells are called coelomocytes
Mollusca , urochordates body cavity is filled
With hemocele, cells are hemocytes
Amebocytes are seen in urochordates
Invertebrates respond to local injury by
Phagocytosis
Encapsulation(similar to granuloma formation)
Neutralization of noxious stimuli by hypertrophy of
cells
Chemical mediators are also seen in some
invertebrates
A F Rowley The evolution of inflammation ; journal of
inflammation vol-5 1996
CAUSES OF INFLAMMATION
LIVING
Bacteria
Viruses
Mycoplasma
Fungi
Protozoa
Parasites
Non living
Trauma - osteomyelitis Heat – burns
Ionizing radiation Uv light, infared
Chemicals , acids, alkalies Foreign body
Idiopathic
GENETIC VARIATIONS
Variations in inherited genes can place them
at risk/ predispose them to inflammatory Disease.
These usually don’t cause disease by themselves
Unless they are challenged by particular trigger
CARDINAL SIGNS OF
INFLAMMATION
Celsus (1St century)
1. RUBOR - redness
2. TUMOR - swelling
3. CALOR - heat
4. DOLOR - pain
FUNCTIO LAESA – loss of function (later added
by galen and virchow in 3rd century)
Rubor
Redness is due to
VASODILATION (DUE TO RELEASE OF MEDIATORS)
INCREASED BLOOD SUPPLY
TRIPLE RESPONSE OF LEWIS(1924)
RED LINE APPEARS IN A
FEW SECONDS
DUE TO VASODILATION OF
CAPILLARIE AND VENULE
FLARE
FLUSH AROUND
RED LINE
APPEARS SLOWLY DUE TO AXON REFLEX
CAUSING DILATION OF
ADJACENT ARTERIOLES
WHEAL
SWELLING
OEDEMA
APPEARS IN MINUTES DUE TO TRANSUDATION OF
FLUID INTO EXTRA VASCULAR
SPACE
CALOR
Due to increase in blood supply
Due to increase in metabolic activity in that area
Appreciation of heat is possible in superficial areas
with heat receptors… e.g : skin subcutaneous tissues
In deeper organs although associated with heat
in the area , it is not associated with perception of
increased heat
Due to release of mediators which stimulate nerve
endings
Occurs only when appropriate sensory N. endings
exists in inflamed area
Type of pain depends on extent of stimulus rather
than type of causative agent
REFERRED PAIN:
 Due to spread of pain stimuli along the
nerves to relevant spinal segment and relay of
pain sensation to other areas served by same
segmental distribution
 E.g Pain of myocardial ischemia referred to
left shoulder
PAIN CAUSED BY
INFLAMMATION OF
CHARACTER
SKIN BURNING , ITCHING
DENSE TISSUES LIKE PERITONIUM
BONE , ENCAPSULATED ORGANS DULL , BORING , ACHING
PROGRESSED TO SUPPURATION THROBBING
PUS REACHES TO SURFACE SHARP , DARTING ,LANCINATING
NERVE TRUNK BORING , TINGLING
TUMOR/SWELLING
Due to increased vascularity
Accumulation of fluid and cells in damaged part
EDEMA- Excess fluid in interstitial / serous cavities
it may be exudate / transudate in nature
PUS: Purulent exudate rich in leukocytes(mostly
neutrophils), debris of dead cells and in many cases
microbes
EXUDATE TRANSUDATE
Edema of inflammed tissues
due to alteration in normal permeability
of small bvs
Ultrafiltrate of blood plasma that results from
osmotic/hydrostatic imbalance across the
vessel wall
Inflammatory edema Non inflammatory edema
High protein(2.5-3.5g/dl) readily coagulates
due to high fibrinogen
Low protein (>1g/dl)mainly albumin
low fibrinogen, no tendency to coagulate
Specific gravity >1.018
ph <7.3
Specific gravity low<1.015
ph>7.3
Glucose is low(<60mg/dl) same as plasma
LDH is high LDH is low
Many cells, inflammatory , parenchymal cells Few cells mainly mesothelial cells and cellular
debris
e.g: purulent exudate such as pus Edema in congestive cardiac failure
TYPES OF INFLAMMATION
Acute inflammation
Rapid response to an injurious agent that serves to
deliver mediators of host defense , leukocytes and
plasma proteins to the site of injury
Chronic inflammation
Inflammation of prolonged duration in which active
inflammation, tissue destruction, and attempts at
repair are proceeding simultaneously
ACUTE CHRONIC
ONSET IMMEDIATE DELAYED
DURATION FEW DAYS UPTO MONTHS, YEARS
CAUSATIVE AGENTS
BACTERIA
INJURED TISSUES
PERSISTENT ACUTE ,
FOREIGN BODY , VIRAL
AUTOIMMUNE
MAJOR CELLS
NEUTROPHILS ,BASOPHILS
MONOCYTESMACROPHAGES
MONONUCLEAR CELLS
MONO,LYMHPHOCYTES
PLASMA CELLS
FIBROBLASTS
PRIMARY
MEDIATORS
VASOACTIVE AMINES EICOSANOIDS
OUTCOMES
RESOLUTION
ABSCESS FORMATION
CHRONIC INFLAMMATION
TISSUE DESTRUCTION
FIBROSIS
NECROSIS
ACUTE
INFLAMMATION
VASCULAR
HEMODYNAMIC
CHANGES
ALTERED
VASCULAR
PERMEABILITY
CELLULAR
EXUDATION PHAGOCYTOSIS
INJURY
TRANSIENT
VAOCONSTRICTI
ON
MILD
3-5SECONDS
SEVERE
5MINUTES
HEMO
DYNAMIC
CHANGES
PERSISTENT
PROGRESIVE
VASODILATION
INCREASED
BLOOD
VOLUME
LOCAL
ELEVATION OF
HYDROSTATIC
PRESSURE
red heat edema
Five mechanisms of increased vascular
permeability
Venules,vasoactiv
mediators
Imm transient
Venules
IL-1, TNF
DELAYED
Persists till
intercellular
junction
forms
Toxins
Chemicals
Imm,
sustained
1.Mediators bind to endothelium
 Activates intracellular signaling pathways
 Lead to phosphorylation of contractile proteins like
myosin
 Imm…….15 to 30 minutes……..so transient
2.Cytokines cause structural reorganisation of
cytoskeleton causing retraction
3. Direct injury……….sustained…….till vessel wall
repaired
4. Neutrophils while migrating secrete proteases, ros
 In places like bbb tight junctions exisist
between endothelial cells
 Cell cytoplasm communicates with exterior
through a process called transcytosis
 Vesicles are formed from cytoplasm
 Called vesiculovacular organelle
 In infl……inc VDGF..............inc in no these
channels…..leadin to inc vas.perm
INCREASED
VASCULAR
PERMEABILITY
ESCAPE
OF
PROTEINS
FLUID
DECREASE
INTRAVAS
CULAR
OSMOTIC
PRESSURE
INCREASED
OSMOTIC
PRESSURE OF
INTERSTITIAL
FLUID
OUT
FLOW
OF FLUID
INCREASED
CONCENTRATION
OF BLOOD CELLS
RAISED
VISCOSITY
SLOWING
STASIS
CELLULAR EVENTS
EXUDATION
The escape of fluid, protein, and blood cells from
vascular system into interstitial tissue/body cavities
Changes leading to migration are
Changes in formed elements of blood
Rolling and Adhesion ,Emigration
Chemotaxis
NORMAL
AXIAL FLOW
• RBC , WBC in the centre
• Peripheral zone of plasma
INFLAMMATION
• Leakage of plasma-narrowing of peripheral zone
• Redistribution of leukocytes to periphery-
MARGINATION
EMIGRATION
• Endothelium is virtually lined by leukocytes –pavementing
• Tumble slowly , adhere transiently –ROLLING ADHESION
• After firm adhesion leukocytes insert pseudopods into
intercellular junctions and escape into extra vascular space
Inflammation
ADHESION MOLECULES INVOLVED IN INFLAMMATION
SELECTINS
3 closely related proteins( P, E , L) function in adhesion
They differ in their cellular distribution
L-SELECTIN/CD62L
Expressed in lymphocytes/other leukocytes
Founds on tips of microvillus projection of leukocytes
Facilitating it interaction with ligands on endothelium
E-SELECTIN
Previously know as endothelial leukocyte
adhesion molecule
Expressed on cytokine activated endothelial cells
P-SELECTIN
Present on secretory granules of platelets
also found in granules of endothelial cells
INTEGRINS
30 structurally homologus proteins
promote cell-cell/cell-matrix interactions
IMMUNOGLOBULIN SUPER FAMILY ADHESION
MOLECULES
ICAM VCAM
Leukocytes express CHOligands for selectins, integrins
These are low affinity reactions
Fast off rate…easily disrupt by flowing blood
As a result bound WBC detach and bind again
roll along endothelial surface
ENDOTHELIAL
MOLECULE
LEUKOCYTE RECEPTOR ROLE
P-SELECTIN SIALYL-LEWIS X ROLLING
E-SELECTIN SIALYL –LEWIS X ROLLING ,ADHESION
ICAM-1 CD 11/CD18 INTEGRINS ADHESION,
TRANSMIGRATION
VCAM-1 ALPHA 4, BETA 1 ADHESION
Inflammation
CHEMOTAXIS
Locomotion oriented along a chemical gradient
Chemokines acts chemoattractants for specific leukocytes
C-X-C Chemokine / alpha chemokine NEUTROPHILS
C-C Chemokine/beta chemokine
Acts On Eosinophils, Basophils, Monocytes, Lymphocytes
e.g: MCP, EOTAXIN
C-Chemokine/gamma LYMPHOCYTES
Chemokines mediate their activities by binding to
seven transmembrane coupled receptor
Receptors are CXCR, CCR, CR
(CXCR-4, CCR-5 act as co receptor for viral envelope
glycoprotein of HIV and thus are involved in entry
and binding of virus)
chemokines stimulate leukocyte recruitment
and control normal migration of cells through various
tissues
Leukocyte activation
Once recruited to site of injury, they must be activated
Stimuli are
 Microbes, Necrotic cells
 Ag-Ab complex
 cytokines
Leukocytes express a number of receptors
on their surface
 Toll like receptors – recognize LPS
 Cytokine receptor
leukocyte activation
PHAGOCYTOSIS
DEFINED AS
Process of engulfment of solid
particulate material by cells
Steps involved are
Recognition and attachment stage
Engulfment stage
Digestion/degradation stage
RECOGNITION AND ATTACHMENT
The process of coating a particle , such as
microbe to target it for phagocytosis is called
OPSONISATION
substances are called opsonins
Main opsonin present in serum are
IGg opsonin(Fc) PMN possess receptor
C3b opsonin
• Tuftsin is a phagocyte enhancing material in serum
• Acts directly on cell to stimulate phagocytosis
• 2 types of disorders
1. congenital an abnormal peptide competitively inhibit
2.deficiency seen in splenectomy
• Due to lack of tuftesin releasing enzyme from spleen.
Engulfment
This is accomplished by formation of pseudopod
around particle due to actin filament beneath cellwall
Eventually complete closure of particle with in a
phagosome created by plasma membrane
Limiting membrane of phagocytic vacuole fuses with
Lysosome - phagolysosome
Inflammation
Inflammation
Oxygen
dependent
Reactive
metabolites
Oxygen
independent
granules of
phagocytic cell
Killing
degrading
Nitric oxide
Oxygen dependent
By production of reactive oxygen metabolites
HOCl , HOI , HOBR , HYDROGEN PEROXIDE, HYDROXYL
NADPH OXIDASE present in cell membrane of
phagosome reduces it to superoxide anion
MPO dependent killing
 MPO acts on hydrogen peroxide in presence of
halides to form hypohalous acid
 This is more potent antibacterial agent
MPO independent killing
 Mature macrophages lack MPO
 They carry out bactericidal actions by
forming hydroxyl ions
Oxygen independent
 Agents released from phagocytic cells
donot require oxygen
 These include
Lysosomal hydrolases
Permeability increasing factors
Defensins
Cationic proteins
Chemical mediators of inflammation
Chemical Mediator Of Inflammation
• Also called permeability factors
• Induce their action by binding to specific
receptors on target cells
• Stimulate target cell to release secondary
effector molecules
Two types:
1. Cell derived
2. Plasma derived
VASOACTIVE
AMINES
ARACHIDONIC
ACID
METABOLITES
LYSOSOMAL
COMPONENTS
PAF
CYTOKINES
NITRIC
OXIDE
CELL
DERIVED
MEDIATORS
Platelets
Neutrophils
Monocytes
Endothelium
Fibroblast
Smooth muscle
Histamine
 First autacoid to be discovered
 Formed from histidine by decarboxylation
 Synthesized in all tissues
 More in skin , lungs , GIT
 Stored in high concentration in mast cells and
basophils
 Involved in inflammation and anaphylactic reactions
HISTAMINE RECEPTORS
RECEPTOR TYPE LOCATION
BIOLOGICAL
EFFECTS
H1 SMOOTH MUSCLE
ENDOTHELIAL CELLS
VD, BRONCHOCONSTRICTION,
ACUTE ALLERGIC RESPONSE
H2 GASTRIC PARIETAL CELLS VD , SECRETION OF GASTRIC
ACID
H3 CNS NEUROTRANSMISSION
MODULATE WAKEFULLNESS
COGNITIVE ABILITY
FOOD CONSUMPTION
H4 MAST CELLS
EOSINOPHILS
T-CELLS
DENDRITIC CELLS
REGULATE IMMUNE
RESPONSE
ROLE IN CHEMOTAXIS
Exocrine glands
salivary , sweat
lacrimal , bronchial secretion
pancreas , gastric
Arterioles , capillaries , venules
Vasodilation , systemic hypotension
Increased permeability(edema)
smooth muscle
Bronchus , uterus, contraction
GIT
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HISTAMINE ANTAGONISTS/ ANTI HISTAMINES
Bovet got nobel prize in 1944
Inhibit action of histamine by blocking receptor
Inhibit enzyme histidine decarboxylase
(atypical antihistamines)
H1 ANTAGONISTS: USED TO TREAT ALLERGY
First generation second generation
Chlorpheneramine Fexofenadine
Diphenhydramine Loratidine
Promethazine, hydroxyzine Levo Cetrizine
serotonin
 Also called 5-hydroxytryptamine(5HT)
 Formed from L-Tryptophan
 Present in platelets and enterochromaffin cells
 Actions are similar to histamine
 Less potent vasodilator than histamine
ARACHIDONIC ACID METABOLITES
 20 CARBON PUFA
 Derived from dietary source
 Conversion of linoleic acid
 Does not occur freely in cell but esterified
in membrane phospholipids
Phospholipase
A2
Cell membrane
phospholipids
Arachidonic acid
PGD2,PGE2,PGF2
PROSTACYCLIN
PGI2
THROMBOXANE
TXA2
PGG2
PGH2+FREE
RADICALS
PHOSPHO
LIPASE A2
Calcium
Various
kinases
Cycloo
oxygenase
Vd
Inhibit
platelet
aggregation
Vasoconstriction
Promotes
aggregation
Vasodilation
Potentiates
edema
Cyclooxygenase
pathway
ARACHIDONIC
ACID
5-HYDROPEROXYEICOSATETRAENOIC ACID
5-HPETE
LEUKOTRIENE A4
LEUKOTRIENE
C4,D4,E4
LEUKOTRIENE
B4
LIPOXIN
A4
LIPOXIN B4
12 LIPO
OXYGENASE
55 LIPO
OXYGEN
ASE
CHEMOTAXIS
5-HETE
VASO,
BRONCHO
CONSTRICTION
INC
PERMEABILITY
CHEMOTAXIS
CELL
ADHESION
VD
Inhibits
CHEMOTAXIS
LIPOOXYGENASE
PATHWAY
MYELOPEROXIDASE
ACID HYDROLASE
NEUTRAL PROTEASE
ELASTASE PROTEINASE
CATHEPSIN
NON SP COLLAGENASE
LYSOZYME
LACTOFERRIN
COLLAGENASE
GELATINASE
HISTAMINASE
PLASMINOGEN
ACTIVATOR
ALKALINE PHOSPHATASE
SMALLER
SPECIFIC
SECONDARY
LARGER
AZUROPHILIC
PRIMARY
LYSOSOMAL COMPONENTS
 Neutral proteases are capable of degrading
various extracellular component
 Collagen, Basement membrane,
 Fibrin, Elastin, Cartilage
 Also cleave C3 and C5 directly releasing
anaphylotoxins
 This results in tissue destruction
Because of its destructive effects ,if initial
leukocyte infiltration if left unchecked results in
tissue damage
PLATELET ACTIVATING FACTOR
Inflammation
IL-1
TNF
ENDOTHELIAL
INCREASED
LEUKOCYTE
ADHERENCE
PGI SYNTHESIS
PROCOAGULANT
ACTIVITY
LEUKOCYTE
EFFECTS
INCREASED
CYTOKINE
SECRETION
IL-1 AND 6
FEVER
INCREASED
SLEEP,ACUTEPHASE
PROTEINS
DECREASED APETITE
NEUTROPHILIA
FIBROBLASTS
INCREASED
PROLIFERATION,
COLLAGEN,PROTEASE
PGE SYNTHESIS
NITRIC OXIDE METABOLITES
 Factor released from ENDOTHELIAL CELLS
 Also called ENDOTHELIAL DERIVED RELAXING
FACTOR
 Also from MACROPHAGES and NEURONS in brain
 Synthesized from L-ARGININE by enzyme
nitric oxide synthetase(NOS)
3 types
eNOS endothelial produced at low levels
nNOS neuronal calcium influx cause rapid production
iNOS inducible (cytokines)
ROLE IN INFLAMMATION
 Potent vasodilator
 Reduces platelet aggregation
 Reduce leukocyte adhesion
 Inhibit several features of mast cell
induced inflammation
 Endogenous regulator for leukocyte recruitment
 No and its derivatives are microbicidal
NO is an endogenous compensatory mechanism
that reduces inflammatory response
Inflammation
kinin
clotting
Fibrino
lytic
comple
ment
PLASMA
DERIVED
COMPLEMENT SYSTEM
 Consists of 20 component proteins and
their cleavage products
 Found in plasma
 Function in both innate and adaptive immunity
 In process of complement activation a number
of components are elaborated that cause
- Increased vascular permeability
- Chemotaxis
- Opsonisation
Inflammation
Inflammation
C3a and C5a
 Stimulate histamine release
 Anaphylotoxins
 They have effects similar to mast cell mediators
C5a
 Activates LOX pathway
 Powerful chemotactic agent
 Role in leukocyte adhesion
C3b
 Acts as opsonin
REGULATION OF COMPLEMENT ACTIVATION
The activation of complement is controlled by
cell associated and circulatory regulatory proteins
Regulation of C3 and C5convertase
 Regulators function by enhancing dissociation
of convertase complex
 E.g: decay accelerating factor
 Proteolytic cleaving of C3b
Binding of active complement components by
specific proteins in plasma
 C1 binding to immune complex is blocked by
C1 INHIBITOR(C1INH)
 Deficiency of C1INH is associated with
HERIDITARY ANGIONEUROTIC EDEMA
Episodic edema in skin, extremities, laryngeal
and intestinal mucosa provoked by stress/trauma
KININ SYSTEM
Hageman factor [XII]
Activated Hageman Factor [XIIa]
prekallikrein activator (fragment of XIIa)
Plasmakallikrein Kallikrein
HMW Kininogen Bradykinin
Contact with
-ve charged
Collagen,Basement
membrane
cofactor for
Activation of
XII
chemotaxis
C5 to C5a
BRADYKININ
 Potent vasodilator
 Increases vascular permeability( lower BP)
 Causes constriction of smooth muscles
 Pain
 But the actions are short lived
 As it is quickly inactivated by kininase
 Any remaining kinin is inactivated by passage of
plasma through lung (degraded by ACE)
SO ACE INHIBITORS PREVENTS
DEGRADATION THERE BY FURTHER LOWERING BP
Ca
PL
FACTOR XIIa
PRE KALLIKREIN KALLIKREIN
PLASMINOGEN PLASMIN FIBRIN FIBRINOGEN
THROMBIN
C3 C3a
KININ
SYSTEM
COMPLEMENT
CLOTTING
SYSTEM
FIBRINOLYTIC
SYSTEM
FACTOR 1 FIBRINOGEN
FACTOR 2 PROTHROMBIN
FACTOR 3 TISSUE FACTOR
FACTOR 4 CALCIUM
FACTOR 5 PROACCELERIN
HMW KININOGEN FITZ GERALD FACTOR
FACTOR 7 PRO CONVERTIN /STABLE FACTOR
SERUM PROTHROMBIN CONVERSION
ACCELERATOR
FACTOR 8 ANTI HEMOPHILIC FACTOR/AHFA
FACTOR 9 PLAS.THROMBOPLASTIN COMP
CHRISTMAS FACTOR / AHB
FACTOR 10 STUART / PROWER
FACTOR 11 PLASMA THROMBOPLASTIN ANTECEDENT
FACTOR 12 HAGEMAN FACTOR
FACTOR 13 FIBRIN STABILISING FACTOR
PRE KALLIKREIN FLETCHER FACTOR
Morphological patterns of acute inflammation
Serous inflammation
 Marked by outpouring of thin fluid
 Derived either from plasma
 Or secretions of mesothelial cells
lining peritoneal, pleural, pericardial cavities
 E.g: skin blister resulting from burn
viral infection causing fluid accumulation
either within or immediately beneath epidermis
Fibrinous inflammation
 Due increased permeability, severe injury large
molecules such as fibrinogen pass vascular barrier
 Fibrin is formed and deposited in extracellular space
 Fibrinous exudates are removed by fibrinolysis,
clearing of debris by macrophages
 If it is not removed it may stimulate ingrowth of
fibroblasts, blood vessels leading to scarring
Suppurative/purulent inflammation
 Characterised by formation of pus
 An accumulation of pus in enclosed
tissue spaces - ABSCESS
 Certain bacteria like staphylococci
produce this localised suppuration
 E.G: Brain abscess
Pyelo nephritis
ULCER
 Is A Break In Continuity Of
Epithelium Due To Necrosis Or
Pathologic Death Of Tissues
Extending Into Submucosa
 Common sites are mucosa of mouth, stomach
 In acute stage infiltration with polymorphs is seen
 In chronic ulcers infiltration by plasma cells,
lymphocytes, macrophages associated with
fibroblastic proliferation
Microbes
Toxins
trauma
ACUTE
INFLAMMATION
RESOLUTION
Clearance of injurious stimuli
, mediators
Replacement of injured cells
Normal function
PROGRESS
HEALING
HEALING
FIBROSIS
Loss of function
LOCALISATION
abscess
HEALING
Chronic inflammation
Angiogenesis
Mononuclear cell
infiltrate
Viral
infections
Persistent injury
Autoimmune
diseases
outcomes
CHRONIC INFLAMMATION
Chronic inflammation is of prolonged
duration(weeks/ months) in which active
inflammation, tissue destruction, and
attempts to repair are proceeding
simultaneously….
CAUSES
1.Persistent infections
 By tubercle bacilli, certain virus, fungi
 These organisms are of low toxicity
 Evoke an immune reaction called
delayed type of hypersensitivity
 Leading to formation of a granuloma
Macrophages
Dendritic cells
critical for induction
of t-h cells
IL-
12
IF
IF-Y
ACTIVATES
MACROPHAGES
CAUSE RELEASE
OF PDGF
FIBROSIS
MECHANISM OF TYPE IV HYPERSENSITIVITY IN FORMATION OF
GRANULOMA
• Antigen binding to mannose receptor(mhc) on
surface of macrophage
• This act as antigen presenting cell
• Ag bearing macrophage(icam-1) interacts with
receptor on t-cells(cd11a cd2)
• Helper t cells - MHC CLASS II
• Cytotoxic t cells – MHC CLASS I
2. Prolonged exposure to potentially toxic agents
Either Exogenous/ Endogenous
 Exogenous : Silica when inhaled for prolonged
periods, results in inflammatory lung disease
SILICOSIS
 Endogenous : Toxic plasma lipid components lead
to inflammatory process of arterial wall
ATHEROSCLEROSIS
3. AUTO IMMUNITY
 Immune reactions develop against individuals own
tissues
 Autoantigens evoke a self perpetuating immune
reaction that results in chronic tissue damage and
inflammation
 E.g: Rheumatoid arthritis
Systemic lupus erythematosus
ROLE OF INFLAMMATION IN AUTOIMMUNITY
Chronic inflammation is characterised by
1. Infiltration with mononuclear cells which include
macrophages, lymphocytes, plasma cells
2. Tissue destruction induced by persistent offending
agent or by inflammatory cells
3. Attempts at healing by connective tissue
replacement of damaged tissue
accomplished by proliferation of blood
vessels (angiogenesis), fibrosis
Mononuclear cell infiltration
 Macrophage is dominant cell in chronic inflammation
 It is component of mononuclear phagocyte
system(MPS)
 Previously called reticuloendothelial system
 Comprises blood monocytes, tissue macrophages
 Half life of blood monocyte is about 1day
 Tissue macrophage is several months to years
Connective tissue(histiocytes)
Spleen(sinusoidal lining cells)
Serous cavity(peritoneal pleural)
Skin(langerhans cells)
Synovia(A cells)
INFLAMMATION
Exudate macrophages
Epitheloid cells
Multi nucleated giant cells
MECHANISM OF MACROPHAGE ACCUMULATION IN
TISSUES ,CONTINUOUS RECRUITMENT FROM
MICROCIRCULATION
STIMULI ARE
CHEMOKINES BY
ACTIVATED
MACROPHAGES
LYMPHOCYTE
MCP-1
C5a
PDGF
TGF-ALPHA
FRAGMENTS FROM
BROKEN COLLAGEN
FIBRONECTIN
CYTOKINES
OXIDISED
LIPIDS
Inflammation
Other cells in chronic inflammation are
 Lymphocytes, plasma cells, eosinophils and mast
cells
 LYMPHOCYTES are involved in both types of immune
reactions(humoral , cell mediated)
 Lymphocytes(B, T) use various adhesion molecules
and chemokines to migrate in to inflammatory sites
 Lymphocytes , macrophages interact in a
bidirectional way
Inflammation
 Microbial ag should be recognised as non self
 This require immunological memory and specificity
 This property resides in lymphocytes
Inflammation
EOSINOPHILS
 Abundant in immune reactions mediated by IgE
 And in parasitic infections
Granules contain major basic protein
 A highly cationic protein toxic to parasites
 Also causes lysis of mammalian epithelial cells
MAST CELLS
 Basophils in tissues
 Participate in both acute and chronic
 Express on their surface receptors
which bind to Fc portion of IgE
 Degranulation cause release of mediators such as
histamine, PAF, eicosanoids, neutral proteases
TYPES OF CHRONIC INFLAMMATION
 When injurious agent causes a characteristic
histological tissue response – SPECIFIC
 E.g: TB , Leprosy
 Histologically characterized by granuloma formation
 when irritant produces a non specific inflammatory
reaction with formation of granulation tissue and
healing by fibrosis – NON SPECIFIC
 E.g: chronic osteomyelitis , ulcer
 Histologically Non specific cell infiltration
GRANULOMATOUS INFLAMMATION
GRANULOMA IS A FOCUS OF CHRONIC
INFLAMMATION CONSISTING OF MICROSCOPIC
AGGREGATION OF MACROPHAGES THAT ARE
TRANSFORMED INTO EPITHELIUM LIKE CELLS
SURROUNDED BY A COLLAR OF MONONUCLEAR
LEUKOCYTES , PRINCIPALLY LYMPHOCYTES ,
OCCASIONAL PLASMA CELLS
Inflammation
BACTERIAL
TB LEPROSY
SYPHILITIC GUMMA
FUNGAL
HISTOPLASMOSIS
BLASTOMYCOSIS
CRYPTOCOCCUS
PARASITIC
SCHISTOSOMIASIS
FOREIGN BODY
SUTURE , ANY
PROSTHESIS ,
VASCULAR GRAFT
INORGANIC
METALS,DUSTS
SILICOSIS
BERYLLOSIS
UN KNOWN
SARCOIDOSIS
Epitheloid cells
They are modified macrophages/
histiocytes which are somewhat elongated, having
pale staining abundant cytoplasm, vesicular, lightly
stained slipper shaped nucleus
 Cell membrane of adjacent epitheloid cell is closely
apposed due to hazy outline
 They are weakly phagocytic
GIANT CELLS
 Formed by fusion of epitheloid cells
 May have 20/more nuclei
 Nuclei present centrally- FOREIGN BODY TYPE
 Nuclei at periphery like horse shoe/ ring/clustered at
two poles- LANGHANS TYPE
 They are also weakly phagocytic
 Produce secretory products which helps to remove
invading agents
NECROSIS
 It is feature of some granulomatous conditions
 E.g: caseation necrosis in TB
FIBROSIS
 Due to proliferation of fibroblasts at periphery of
granuloma
Factors favouring formation of granuloma
1. Presence of poorly digestible irritant
2. Presence of cell mediated immunity to irritant
implying role of hypersensitivity in granulomatous
inflammation
Types of granuloma
1. FOREIGN BODY GRANULOMA : Material can be
seen in center when viewed with polarised light
2. IMMUNE GRANULOMA : Due to microbes capable
of activating cell mediated immunity
SYSTEMIC EFFECTS OF
INFLAMMATION
LPS EXOGENOUS
PYROGENS
TNF,IL-1
ENDOGENOUS
PYROGENS
INCREASE
CYCLOOXYGENASE
PGE2 STIMULATE
RELEASE OF CYCLIC
AMP
RESET
TEMPERATURE
SET POINT AT
HIGHER LEVEL
FEVER
• Temperature > 40C
• Triggers cold receptors
Severe
Inflammation
• Pallor
• A feeling of coldness of skin
surface
Reflex
Vasoconstriction
Of Vessels
RIGOR
Shaking
Exaggerated
shivering which
occurs with a high
fever
Changes in pulse rate
 Increase in temperature accompany increase in
pulse
 For every 1 degree F rise in temp pulse increase by
10beats/minute
 Conversely bradycardia occurs in typhoid fever
Acute phase proteins
 Mostly synthesized in liver
 Clinical concentration increase 100fold in
inflammation
 E.g: CRP, serum amyloid A protein(SAA), Fibrinogen
 Cytokines upregulate their synthesis by stimulating
hepatocytes
 CRP, SAA acts as opsonins and fix complement
They have beneficial effects in acute inflammation
but in chronic prolonged production leads to
secondary amyloidosis
CRP
 Levels increased in infection , inflammation
 Tissue necrosis , malignancy , auto immune diseases
 It binds to phosphocholine on dead / dying cells and
activate complement
 Enhances phagocytosis by microbes
 Marked increase indicates risk for CVD , hypertension
diabetes
LEUKOCYTOSIS
 Common feature of especially for bacterial infections
 Count increase by 15,000 to 20,000cells/cumm
 If it increase up to 1lakh – LEUKEMOID REACTION
(but splenomegaly, lymphadenopathy, hemorrhages
are absent)
MYELOID LEUKEMOID
TB, MENINGITIS
ENDOCARDITIS
BURNS
MERCURY POISONING
LYMPHOID LEUKEMOID
INFECTIOUS
MONONUCLEOSIS
TB, PERTUSIS
CHICKEN POX
MEASLES
INITIAL
INCREASE
ACCELERATED
RELEASE OF
CELLS DUE TO
TNF, IL-1
INCREASE IMMATURE
NEUTROPHILS IN
BLOOD
PROLONGED
INFECTION
INCREASED
COLONY
STIMULATING
FACTORS
INCREASED CELLS FOR
COMPENSATION OF
CELL LOSS
LEUKOCYTOSIS
NEUTROPHILIC LEUKOCYTOSIS BACTERIAL INFECTIONS, MI,
BURNS
EOSINOPHILIC LEUKOCYTOSIS PARASITIC INFESTATIONS,
ASTHMA, ALLERGIES
BASOPHILIC LEUKOCYTOSIS
(RARE)
INDICATIVE OF
MYELOPROLIFERATIVE DISEASE
(CML)
MONOCYTOSIS
(COMMON IN CHRONIC)
TB, ENDOCARDITIS, COLLAGEN
VASCULAR DISEASE(SLE),
INFLAMMATORY BOWEL
DISEASE(ULCERATIVE COLITIS)
LYMPHOCYTOSIS TB, VIRAL(HEP-A, CMV, EBV)
LPS
(TNF, IL-1)
TISSUE
FACTOR
EXPRESSION
BY
ENDOTHELI
AL CELLS
INTIATES
COAGULATI
ON
DIC
CYTOKINES LIVER INJURY
FAILURE TO
MAINTAIN
NORMAL
GLUCOSE
SHOCK
OVER
PRODUCTION OF
NO
BY CYTOKINE
ACTIVATED
CARDIAC
MYOCYTES
HEART FAILURE
DIC
HEART
FAILURE
HYPOGLYCEMIA
SEPTIC
SHOCK
LYMPHANGITIS- LYMPHADENITIS
 Lymphatics and lymphnodes that drain the
inflammed tissue show reactive inflammatory
changes
 This is a non specific reaction to mediators released
from inflammed tissues
 LYMPHANGITIS Inflammation Of Lymphatic Vessels
And Channels
 LYMPHADENITIS Inflammation of lymph node
REGULATION OF INFLAMMATION
1. ACUTE PHASE PROTEINS
Alpha 1 anti trypsin:
 It Is a Protease Inhibitor
 Protects Tissues From Enzymes Of Inflammatory Cells
 Especially Neutrophil Elastase
 In Absence Degradation Of Elastin
 If This Occur In Lungs , This Leads To Respiratory
Problems
 Protease inhibitor
 Hapatglobin
 It Scavangers Hb Released Into Circulation
 Potent Antioxidant
 Resist Cell Oxidative Stress
 Inhibits COX , LOX
2. CORTICOSTEROIDS
 Endogenous glucocorticoids act as anti inflammatory
agents
 Their levels are increased in infection , trauma by self
regulating mechanism
3. Supressor T cells / regulator T cells
 Modulate immune system
 Maintain tolerance to self antigens
4. Anti inflammatory chemical mediators
propree
RESOLVINS
RvS
OMEGA 3
FACTORS DETERMINING
VARIATIONS IN INFLAMMATORY
RESPONSE
FACTORS INVOLVING THE ORGANISM
Type of injury and infection
 Lung reacts to pneumococci by occurrence of
pneumonia
 While it responds to tubercle bacilli by
granulomatous inflammation
Dose
 Concentration of organism in small dose form local
lesions
 Large dose cause severe spreading infections
Portal Of Entry
 Vibrio cholera is not pathogenic if injected sub
cutaneously but cause cholera if swallowed
Product Of Organisms
 Certain products cause spread of infection
 e.g : streptokinase by streptococci
coagulase by staphylococci
FACTORS INVOLVING THE HOST
1. AGE : very young, very old are less able to combat
infection because of lack of inflammatory response
Many elderly patients respond with a chronic
inflammatory response which in young patients have
provoked acute response
2. DAMAGE TO BONE MARROW AND RETICULO
ENDOTHELIAL SYSTEM
3. ANTIBIOTIC THERAPY
 Antibiotics decrease inflammation because clearing
infection removes reason for inflammation
 Inflammatory response is modified depending on
how the agent respond to therapy
4. Diet
 when you eat your body forms PG’s from nutrients
in diet
 This can be inflammatory / anti inflammatory
 Imbalance in diet leads to formation of
inflammatory PG
 On other hand omega-3 fatty acids , antoxidants ,
phyto nutrients can produce anti inflammatory PG
FOODS HIGH
SATURATED FAT
MEAT EGGS DAIRY
PRODUCTS
COFFEE
CONTAINS CRP
PROCESSED MEATS
COOKING FOODS AT
HIGH TEMP
CAUSE RELEASE OF
TOXINS
TRANS FAT
INTAKE OF
PROCESSED FRIED
FOODS
HIGH GLYCEMIC
INDEX CHO
INSULIN CAUSE
METABOLISM OF AA
PRO INFLAMMATORY FOODS
ANTI
INFLAMMATORY
FOODS
CONCLUSSION
WAR AND INFLAMMATION
 Both are stereotyped responses to outside threats
 There are specialised troops(immune cells)
 Supply routes(vessels)
 Communication and intelligence(mediators)
 Huge array of lethal weapons(enzymes)
IN WAR AS IN INFLAMMATION THERE IS
DAMAGE TO BOTH ENEMY AND FRIENDLY FORCES
AND SEVERE DAMAGE TO BATTLE FIELD ITSELF
PROBABLY YOUR OWN
DEATH WILL BE CAUSED
BY YOUR LAST
INFLAMMATORY
RESPONSE
References
1. Robbins and Cotran Pathologic Basis
of Disease 7th edition
2. Guyton and Hall Text Book of Medical
Physiology 11th edition
3. Harsh Mohan Text Book of Pathology
5th edition
PRESENTED BY
ANUSHA.V
PG-1ST YEAR
Inflammation

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Inflammation

  • 1. INFLAMMATION Enflammare Set a fire Presented by Anusha Vaddi MDS Narayana dental college
  • 2. 1. INTRODUCTION 2. HISTORY 3. CAUSES 4. CARDINAL SIGNS 5. TYPES OF INFLAMMATION 6. ACUTE INFLAMMATION VASCULAR EVENTS CELLULAR EVENTS
  • 3. 7. CHEMICAL MEDIATORS 8. MORPHOLOGICAL PATTERNS OF ACUTE INFLAMMATION 9. CHRONIC INFLAMMATION 10. SYSTEMIC EFFECTS OF INFLAMMATION 11.REGULATORS OF INFLAMMATION 12. FACTORS DETERMINIG VARIATIONS IN RESPONSE
  • 4. Introduction Defined as “Local response of living tissues to injury due to any agent”  Fundamentally protective response  Ultimate goal is to get rid of intial cause cell injury(microbes, toxins)  Consequence of such injury(necrosis, tissues)  without inflammation wounds go unchecked, never heal
  • 5. HISTORICAL HIGHLIGHTS 3000B.C Egyptians first described 1st century Celsus described cardinal signs 1793 John hunter inflammation not disease, non specific response that has salutary effect on host 1839 Conheihm used microscope to observe changes in vessels
  • 6. 1880 Metchinkoff discovered phagocytosis Paul ehrlich proposed humoral theory of immunity 1908 Both got nobel prize 1924 Lewis explained role of chemical mediators in inflammation
  • 8. EVOLUTION OF INFLAMMATION Sponges , coelenterates body cavity is filled with coelum, cells are called coelomocytes Mollusca , urochordates body cavity is filled With hemocele, cells are hemocytes Amebocytes are seen in urochordates
  • 9. Invertebrates respond to local injury by Phagocytosis Encapsulation(similar to granuloma formation) Neutralization of noxious stimuli by hypertrophy of cells Chemical mediators are also seen in some invertebrates A F Rowley The evolution of inflammation ; journal of inflammation vol-5 1996
  • 11. Non living Trauma - osteomyelitis Heat – burns Ionizing radiation Uv light, infared Chemicals , acids, alkalies Foreign body Idiopathic
  • 12. GENETIC VARIATIONS Variations in inherited genes can place them at risk/ predispose them to inflammatory Disease. These usually don’t cause disease by themselves Unless they are challenged by particular trigger
  • 13. CARDINAL SIGNS OF INFLAMMATION Celsus (1St century) 1. RUBOR - redness 2. TUMOR - swelling 3. CALOR - heat 4. DOLOR - pain
  • 14. FUNCTIO LAESA – loss of function (later added by galen and virchow in 3rd century)
  • 15. Rubor Redness is due to VASODILATION (DUE TO RELEASE OF MEDIATORS) INCREASED BLOOD SUPPLY TRIPLE RESPONSE OF LEWIS(1924)
  • 16. RED LINE APPEARS IN A FEW SECONDS DUE TO VASODILATION OF CAPILLARIE AND VENULE FLARE FLUSH AROUND RED LINE APPEARS SLOWLY DUE TO AXON REFLEX CAUSING DILATION OF ADJACENT ARTERIOLES WHEAL SWELLING OEDEMA APPEARS IN MINUTES DUE TO TRANSUDATION OF FLUID INTO EXTRA VASCULAR SPACE
  • 17. CALOR Due to increase in blood supply Due to increase in metabolic activity in that area Appreciation of heat is possible in superficial areas with heat receptors… e.g : skin subcutaneous tissues In deeper organs although associated with heat in the area , it is not associated with perception of increased heat
  • 18. Due to release of mediators which stimulate nerve endings Occurs only when appropriate sensory N. endings exists in inflamed area Type of pain depends on extent of stimulus rather than type of causative agent
  • 19. REFERRED PAIN:  Due to spread of pain stimuli along the nerves to relevant spinal segment and relay of pain sensation to other areas served by same segmental distribution  E.g Pain of myocardial ischemia referred to left shoulder
  • 20. PAIN CAUSED BY INFLAMMATION OF CHARACTER SKIN BURNING , ITCHING DENSE TISSUES LIKE PERITONIUM BONE , ENCAPSULATED ORGANS DULL , BORING , ACHING PROGRESSED TO SUPPURATION THROBBING PUS REACHES TO SURFACE SHARP , DARTING ,LANCINATING NERVE TRUNK BORING , TINGLING
  • 21. TUMOR/SWELLING Due to increased vascularity Accumulation of fluid and cells in damaged part EDEMA- Excess fluid in interstitial / serous cavities it may be exudate / transudate in nature PUS: Purulent exudate rich in leukocytes(mostly neutrophils), debris of dead cells and in many cases microbes
  • 22. EXUDATE TRANSUDATE Edema of inflammed tissues due to alteration in normal permeability of small bvs Ultrafiltrate of blood plasma that results from osmotic/hydrostatic imbalance across the vessel wall Inflammatory edema Non inflammatory edema High protein(2.5-3.5g/dl) readily coagulates due to high fibrinogen Low protein (>1g/dl)mainly albumin low fibrinogen, no tendency to coagulate Specific gravity >1.018 ph <7.3 Specific gravity low<1.015 ph>7.3 Glucose is low(<60mg/dl) same as plasma LDH is high LDH is low Many cells, inflammatory , parenchymal cells Few cells mainly mesothelial cells and cellular debris e.g: purulent exudate such as pus Edema in congestive cardiac failure
  • 23. TYPES OF INFLAMMATION Acute inflammation Rapid response to an injurious agent that serves to deliver mediators of host defense , leukocytes and plasma proteins to the site of injury Chronic inflammation Inflammation of prolonged duration in which active inflammation, tissue destruction, and attempts at repair are proceeding simultaneously
  • 24. ACUTE CHRONIC ONSET IMMEDIATE DELAYED DURATION FEW DAYS UPTO MONTHS, YEARS CAUSATIVE AGENTS BACTERIA INJURED TISSUES PERSISTENT ACUTE , FOREIGN BODY , VIRAL AUTOIMMUNE MAJOR CELLS NEUTROPHILS ,BASOPHILS MONOCYTESMACROPHAGES MONONUCLEAR CELLS MONO,LYMHPHOCYTES PLASMA CELLS FIBROBLASTS PRIMARY MEDIATORS VASOACTIVE AMINES EICOSANOIDS OUTCOMES RESOLUTION ABSCESS FORMATION CHRONIC INFLAMMATION TISSUE DESTRUCTION FIBROSIS NECROSIS
  • 27. Five mechanisms of increased vascular permeability Venules,vasoactiv mediators Imm transient Venules IL-1, TNF DELAYED Persists till intercellular junction forms Toxins Chemicals Imm, sustained
  • 28. 1.Mediators bind to endothelium  Activates intracellular signaling pathways  Lead to phosphorylation of contractile proteins like myosin  Imm…….15 to 30 minutes……..so transient 2.Cytokines cause structural reorganisation of cytoskeleton causing retraction 3. Direct injury……….sustained…….till vessel wall repaired 4. Neutrophils while migrating secrete proteases, ros
  • 29.  In places like bbb tight junctions exisist between endothelial cells  Cell cytoplasm communicates with exterior through a process called transcytosis  Vesicles are formed from cytoplasm  Called vesiculovacular organelle  In infl……inc VDGF..............inc in no these channels…..leadin to inc vas.perm
  • 31. CELLULAR EVENTS EXUDATION The escape of fluid, protein, and blood cells from vascular system into interstitial tissue/body cavities Changes leading to migration are Changes in formed elements of blood Rolling and Adhesion ,Emigration Chemotaxis
  • 32. NORMAL AXIAL FLOW • RBC , WBC in the centre • Peripheral zone of plasma INFLAMMATION • Leakage of plasma-narrowing of peripheral zone • Redistribution of leukocytes to periphery- MARGINATION EMIGRATION • Endothelium is virtually lined by leukocytes –pavementing • Tumble slowly , adhere transiently –ROLLING ADHESION • After firm adhesion leukocytes insert pseudopods into intercellular junctions and escape into extra vascular space
  • 34. ADHESION MOLECULES INVOLVED IN INFLAMMATION SELECTINS 3 closely related proteins( P, E , L) function in adhesion They differ in their cellular distribution L-SELECTIN/CD62L Expressed in lymphocytes/other leukocytes Founds on tips of microvillus projection of leukocytes Facilitating it interaction with ligands on endothelium
  • 35. E-SELECTIN Previously know as endothelial leukocyte adhesion molecule Expressed on cytokine activated endothelial cells P-SELECTIN Present on secretory granules of platelets also found in granules of endothelial cells
  • 36. INTEGRINS 30 structurally homologus proteins promote cell-cell/cell-matrix interactions IMMUNOGLOBULIN SUPER FAMILY ADHESION MOLECULES ICAM VCAM Leukocytes express CHOligands for selectins, integrins These are low affinity reactions Fast off rate…easily disrupt by flowing blood As a result bound WBC detach and bind again roll along endothelial surface
  • 37. ENDOTHELIAL MOLECULE LEUKOCYTE RECEPTOR ROLE P-SELECTIN SIALYL-LEWIS X ROLLING E-SELECTIN SIALYL –LEWIS X ROLLING ,ADHESION ICAM-1 CD 11/CD18 INTEGRINS ADHESION, TRANSMIGRATION VCAM-1 ALPHA 4, BETA 1 ADHESION
  • 39. CHEMOTAXIS Locomotion oriented along a chemical gradient Chemokines acts chemoattractants for specific leukocytes C-X-C Chemokine / alpha chemokine NEUTROPHILS C-C Chemokine/beta chemokine Acts On Eosinophils, Basophils, Monocytes, Lymphocytes e.g: MCP, EOTAXIN C-Chemokine/gamma LYMPHOCYTES
  • 40. Chemokines mediate their activities by binding to seven transmembrane coupled receptor Receptors are CXCR, CCR, CR (CXCR-4, CCR-5 act as co receptor for viral envelope glycoprotein of HIV and thus are involved in entry and binding of virus) chemokines stimulate leukocyte recruitment and control normal migration of cells through various tissues
  • 41. Leukocyte activation Once recruited to site of injury, they must be activated Stimuli are  Microbes, Necrotic cells  Ag-Ab complex  cytokines Leukocytes express a number of receptors on their surface  Toll like receptors – recognize LPS  Cytokine receptor
  • 43. PHAGOCYTOSIS DEFINED AS Process of engulfment of solid particulate material by cells Steps involved are Recognition and attachment stage Engulfment stage Digestion/degradation stage
  • 44. RECOGNITION AND ATTACHMENT The process of coating a particle , such as microbe to target it for phagocytosis is called OPSONISATION substances are called opsonins Main opsonin present in serum are IGg opsonin(Fc) PMN possess receptor C3b opsonin
  • 45. • Tuftsin is a phagocyte enhancing material in serum • Acts directly on cell to stimulate phagocytosis • 2 types of disorders 1. congenital an abnormal peptide competitively inhibit 2.deficiency seen in splenectomy • Due to lack of tuftesin releasing enzyme from spleen.
  • 46. Engulfment This is accomplished by formation of pseudopod around particle due to actin filament beneath cellwall Eventually complete closure of particle with in a phagosome created by plasma membrane Limiting membrane of phagocytic vacuole fuses with Lysosome - phagolysosome
  • 50. Oxygen dependent By production of reactive oxygen metabolites HOCl , HOI , HOBR , HYDROGEN PEROXIDE, HYDROXYL NADPH OXIDASE present in cell membrane of phagosome reduces it to superoxide anion
  • 51. MPO dependent killing  MPO acts on hydrogen peroxide in presence of halides to form hypohalous acid  This is more potent antibacterial agent
  • 52. MPO independent killing  Mature macrophages lack MPO  They carry out bactericidal actions by forming hydroxyl ions
  • 53. Oxygen independent  Agents released from phagocytic cells donot require oxygen  These include Lysosomal hydrolases Permeability increasing factors Defensins Cationic proteins
  • 54. Chemical mediators of inflammation
  • 55. Chemical Mediator Of Inflammation • Also called permeability factors • Induce their action by binding to specific receptors on target cells • Stimulate target cell to release secondary effector molecules Two types: 1. Cell derived 2. Plasma derived
  • 57. Histamine  First autacoid to be discovered  Formed from histidine by decarboxylation  Synthesized in all tissues  More in skin , lungs , GIT  Stored in high concentration in mast cells and basophils  Involved in inflammation and anaphylactic reactions
  • 58. HISTAMINE RECEPTORS RECEPTOR TYPE LOCATION BIOLOGICAL EFFECTS H1 SMOOTH MUSCLE ENDOTHELIAL CELLS VD, BRONCHOCONSTRICTION, ACUTE ALLERGIC RESPONSE H2 GASTRIC PARIETAL CELLS VD , SECRETION OF GASTRIC ACID H3 CNS NEUROTRANSMISSION MODULATE WAKEFULLNESS COGNITIVE ABILITY FOOD CONSUMPTION H4 MAST CELLS EOSINOPHILS T-CELLS DENDRITIC CELLS REGULATE IMMUNE RESPONSE ROLE IN CHEMOTAXIS
  • 59. Exocrine glands salivary , sweat lacrimal , bronchial secretion pancreas , gastric Arterioles , capillaries , venules Vasodilation , systemic hypotension Increased permeability(edema) smooth muscle Bronchus , uterus, contraction GIT
  • 60. Screen clipping taken: 1/5/2013, 7:29 PM Screen clipping taken: 1/5/2013, 7:16 PM Screen clipping taken: 1/5/2013, 7:12 PM Screen clipping taken: 1/5/2013, 5:40 PM
  • 61. HISTAMINE ANTAGONISTS/ ANTI HISTAMINES Bovet got nobel prize in 1944 Inhibit action of histamine by blocking receptor Inhibit enzyme histidine decarboxylase (atypical antihistamines) H1 ANTAGONISTS: USED TO TREAT ALLERGY First generation second generation Chlorpheneramine Fexofenadine Diphenhydramine Loratidine Promethazine, hydroxyzine Levo Cetrizine
  • 62. serotonin  Also called 5-hydroxytryptamine(5HT)  Formed from L-Tryptophan  Present in platelets and enterochromaffin cells  Actions are similar to histamine  Less potent vasodilator than histamine
  • 63. ARACHIDONIC ACID METABOLITES  20 CARBON PUFA  Derived from dietary source  Conversion of linoleic acid  Does not occur freely in cell but esterified in membrane phospholipids
  • 65. Cell membrane phospholipids Arachidonic acid PGD2,PGE2,PGF2 PROSTACYCLIN PGI2 THROMBOXANE TXA2 PGG2 PGH2+FREE RADICALS PHOSPHO LIPASE A2 Calcium Various kinases Cycloo oxygenase Vd Inhibit platelet aggregation Vasoconstriction Promotes aggregation Vasodilation Potentiates edema Cyclooxygenase pathway
  • 66. ARACHIDONIC ACID 5-HYDROPEROXYEICOSATETRAENOIC ACID 5-HPETE LEUKOTRIENE A4 LEUKOTRIENE C4,D4,E4 LEUKOTRIENE B4 LIPOXIN A4 LIPOXIN B4 12 LIPO OXYGENASE 55 LIPO OXYGEN ASE CHEMOTAXIS 5-HETE VASO, BRONCHO CONSTRICTION INC PERMEABILITY CHEMOTAXIS CELL ADHESION VD Inhibits CHEMOTAXIS LIPOOXYGENASE PATHWAY
  • 67. MYELOPEROXIDASE ACID HYDROLASE NEUTRAL PROTEASE ELASTASE PROTEINASE CATHEPSIN NON SP COLLAGENASE LYSOZYME LACTOFERRIN COLLAGENASE GELATINASE HISTAMINASE PLASMINOGEN ACTIVATOR ALKALINE PHOSPHATASE SMALLER SPECIFIC SECONDARY LARGER AZUROPHILIC PRIMARY LYSOSOMAL COMPONENTS
  • 68.  Neutral proteases are capable of degrading various extracellular component  Collagen, Basement membrane,  Fibrin, Elastin, Cartilage  Also cleave C3 and C5 directly releasing anaphylotoxins  This results in tissue destruction Because of its destructive effects ,if initial leukocyte infiltration if left unchecked results in tissue damage
  • 71. IL-1 TNF ENDOTHELIAL INCREASED LEUKOCYTE ADHERENCE PGI SYNTHESIS PROCOAGULANT ACTIVITY LEUKOCYTE EFFECTS INCREASED CYTOKINE SECRETION IL-1 AND 6 FEVER INCREASED SLEEP,ACUTEPHASE PROTEINS DECREASED APETITE NEUTROPHILIA FIBROBLASTS INCREASED PROLIFERATION, COLLAGEN,PROTEASE PGE SYNTHESIS
  • 72. NITRIC OXIDE METABOLITES  Factor released from ENDOTHELIAL CELLS  Also called ENDOTHELIAL DERIVED RELAXING FACTOR  Also from MACROPHAGES and NEURONS in brain  Synthesized from L-ARGININE by enzyme nitric oxide synthetase(NOS) 3 types eNOS endothelial produced at low levels nNOS neuronal calcium influx cause rapid production iNOS inducible (cytokines)
  • 73. ROLE IN INFLAMMATION  Potent vasodilator  Reduces platelet aggregation  Reduce leukocyte adhesion  Inhibit several features of mast cell induced inflammation  Endogenous regulator for leukocyte recruitment  No and its derivatives are microbicidal NO is an endogenous compensatory mechanism that reduces inflammatory response
  • 76. COMPLEMENT SYSTEM  Consists of 20 component proteins and their cleavage products  Found in plasma  Function in both innate and adaptive immunity  In process of complement activation a number of components are elaborated that cause - Increased vascular permeability - Chemotaxis - Opsonisation
  • 79. C3a and C5a  Stimulate histamine release  Anaphylotoxins  They have effects similar to mast cell mediators C5a  Activates LOX pathway  Powerful chemotactic agent  Role in leukocyte adhesion C3b  Acts as opsonin
  • 80. REGULATION OF COMPLEMENT ACTIVATION The activation of complement is controlled by cell associated and circulatory regulatory proteins Regulation of C3 and C5convertase  Regulators function by enhancing dissociation of convertase complex  E.g: decay accelerating factor  Proteolytic cleaving of C3b
  • 81. Binding of active complement components by specific proteins in plasma  C1 binding to immune complex is blocked by C1 INHIBITOR(C1INH)  Deficiency of C1INH is associated with HERIDITARY ANGIONEUROTIC EDEMA Episodic edema in skin, extremities, laryngeal and intestinal mucosa provoked by stress/trauma
  • 82. KININ SYSTEM Hageman factor [XII] Activated Hageman Factor [XIIa] prekallikrein activator (fragment of XIIa) Plasmakallikrein Kallikrein HMW Kininogen Bradykinin Contact with -ve charged Collagen,Basement membrane cofactor for Activation of XII chemotaxis C5 to C5a
  • 83. BRADYKININ  Potent vasodilator  Increases vascular permeability( lower BP)  Causes constriction of smooth muscles  Pain  But the actions are short lived  As it is quickly inactivated by kininase  Any remaining kinin is inactivated by passage of plasma through lung (degraded by ACE) SO ACE INHIBITORS PREVENTS DEGRADATION THERE BY FURTHER LOWERING BP
  • 84. Ca PL
  • 85. FACTOR XIIa PRE KALLIKREIN KALLIKREIN PLASMINOGEN PLASMIN FIBRIN FIBRINOGEN THROMBIN C3 C3a KININ SYSTEM COMPLEMENT CLOTTING SYSTEM FIBRINOLYTIC SYSTEM
  • 86. FACTOR 1 FIBRINOGEN FACTOR 2 PROTHROMBIN FACTOR 3 TISSUE FACTOR FACTOR 4 CALCIUM FACTOR 5 PROACCELERIN HMW KININOGEN FITZ GERALD FACTOR FACTOR 7 PRO CONVERTIN /STABLE FACTOR SERUM PROTHROMBIN CONVERSION ACCELERATOR FACTOR 8 ANTI HEMOPHILIC FACTOR/AHFA FACTOR 9 PLAS.THROMBOPLASTIN COMP CHRISTMAS FACTOR / AHB FACTOR 10 STUART / PROWER FACTOR 11 PLASMA THROMBOPLASTIN ANTECEDENT FACTOR 12 HAGEMAN FACTOR FACTOR 13 FIBRIN STABILISING FACTOR PRE KALLIKREIN FLETCHER FACTOR
  • 87. Morphological patterns of acute inflammation Serous inflammation  Marked by outpouring of thin fluid  Derived either from plasma  Or secretions of mesothelial cells lining peritoneal, pleural, pericardial cavities  E.g: skin blister resulting from burn viral infection causing fluid accumulation either within or immediately beneath epidermis
  • 88. Fibrinous inflammation  Due increased permeability, severe injury large molecules such as fibrinogen pass vascular barrier  Fibrin is formed and deposited in extracellular space  Fibrinous exudates are removed by fibrinolysis, clearing of debris by macrophages  If it is not removed it may stimulate ingrowth of fibroblasts, blood vessels leading to scarring
  • 89. Suppurative/purulent inflammation  Characterised by formation of pus  An accumulation of pus in enclosed tissue spaces - ABSCESS  Certain bacteria like staphylococci produce this localised suppuration  E.G: Brain abscess Pyelo nephritis
  • 90. ULCER  Is A Break In Continuity Of Epithelium Due To Necrosis Or Pathologic Death Of Tissues Extending Into Submucosa  Common sites are mucosa of mouth, stomach  In acute stage infiltration with polymorphs is seen  In chronic ulcers infiltration by plasma cells, lymphocytes, macrophages associated with fibroblastic proliferation
  • 91. Microbes Toxins trauma ACUTE INFLAMMATION RESOLUTION Clearance of injurious stimuli , mediators Replacement of injured cells Normal function PROGRESS HEALING HEALING FIBROSIS Loss of function LOCALISATION abscess HEALING Chronic inflammation Angiogenesis Mononuclear cell infiltrate Viral infections Persistent injury Autoimmune diseases outcomes
  • 92. CHRONIC INFLAMMATION Chronic inflammation is of prolonged duration(weeks/ months) in which active inflammation, tissue destruction, and attempts to repair are proceeding simultaneously….
  • 93. CAUSES 1.Persistent infections  By tubercle bacilli, certain virus, fungi  These organisms are of low toxicity  Evoke an immune reaction called delayed type of hypersensitivity  Leading to formation of a granuloma
  • 94. Macrophages Dendritic cells critical for induction of t-h cells IL- 12 IF IF-Y ACTIVATES MACROPHAGES CAUSE RELEASE OF PDGF FIBROSIS MECHANISM OF TYPE IV HYPERSENSITIVITY IN FORMATION OF GRANULOMA
  • 95. • Antigen binding to mannose receptor(mhc) on surface of macrophage • This act as antigen presenting cell • Ag bearing macrophage(icam-1) interacts with receptor on t-cells(cd11a cd2) • Helper t cells - MHC CLASS II • Cytotoxic t cells – MHC CLASS I
  • 96. 2. Prolonged exposure to potentially toxic agents Either Exogenous/ Endogenous  Exogenous : Silica when inhaled for prolonged periods, results in inflammatory lung disease SILICOSIS  Endogenous : Toxic plasma lipid components lead to inflammatory process of arterial wall ATHEROSCLEROSIS
  • 97. 3. AUTO IMMUNITY  Immune reactions develop against individuals own tissues  Autoantigens evoke a self perpetuating immune reaction that results in chronic tissue damage and inflammation  E.g: Rheumatoid arthritis Systemic lupus erythematosus
  • 98. ROLE OF INFLAMMATION IN AUTOIMMUNITY
  • 99. Chronic inflammation is characterised by 1. Infiltration with mononuclear cells which include macrophages, lymphocytes, plasma cells 2. Tissue destruction induced by persistent offending agent or by inflammatory cells 3. Attempts at healing by connective tissue replacement of damaged tissue accomplished by proliferation of blood vessels (angiogenesis), fibrosis
  • 100. Mononuclear cell infiltration  Macrophage is dominant cell in chronic inflammation  It is component of mononuclear phagocyte system(MPS)  Previously called reticuloendothelial system  Comprises blood monocytes, tissue macrophages  Half life of blood monocyte is about 1day  Tissue macrophage is several months to years
  • 101. Connective tissue(histiocytes) Spleen(sinusoidal lining cells) Serous cavity(peritoneal pleural) Skin(langerhans cells) Synovia(A cells) INFLAMMATION Exudate macrophages Epitheloid cells Multi nucleated giant cells
  • 102. MECHANISM OF MACROPHAGE ACCUMULATION IN TISSUES ,CONTINUOUS RECRUITMENT FROM MICROCIRCULATION STIMULI ARE CHEMOKINES BY ACTIVATED MACROPHAGES LYMPHOCYTE MCP-1 C5a PDGF TGF-ALPHA FRAGMENTS FROM BROKEN COLLAGEN FIBRONECTIN CYTOKINES OXIDISED LIPIDS
  • 104. Other cells in chronic inflammation are  Lymphocytes, plasma cells, eosinophils and mast cells  LYMPHOCYTES are involved in both types of immune reactions(humoral , cell mediated)  Lymphocytes(B, T) use various adhesion molecules and chemokines to migrate in to inflammatory sites  Lymphocytes , macrophages interact in a bidirectional way
  • 106.  Microbial ag should be recognised as non self  This require immunological memory and specificity  This property resides in lymphocytes
  • 108. EOSINOPHILS  Abundant in immune reactions mediated by IgE  And in parasitic infections Granules contain major basic protein  A highly cationic protein toxic to parasites  Also causes lysis of mammalian epithelial cells
  • 109. MAST CELLS  Basophils in tissues  Participate in both acute and chronic  Express on their surface receptors which bind to Fc portion of IgE  Degranulation cause release of mediators such as histamine, PAF, eicosanoids, neutral proteases
  • 110. TYPES OF CHRONIC INFLAMMATION  When injurious agent causes a characteristic histological tissue response – SPECIFIC  E.g: TB , Leprosy  Histologically characterized by granuloma formation  when irritant produces a non specific inflammatory reaction with formation of granulation tissue and healing by fibrosis – NON SPECIFIC  E.g: chronic osteomyelitis , ulcer  Histologically Non specific cell infiltration
  • 111. GRANULOMATOUS INFLAMMATION GRANULOMA IS A FOCUS OF CHRONIC INFLAMMATION CONSISTING OF MICROSCOPIC AGGREGATION OF MACROPHAGES THAT ARE TRANSFORMED INTO EPITHELIUM LIKE CELLS SURROUNDED BY A COLLAR OF MONONUCLEAR LEUKOCYTES , PRINCIPALLY LYMPHOCYTES , OCCASIONAL PLASMA CELLS
  • 113. BACTERIAL TB LEPROSY SYPHILITIC GUMMA FUNGAL HISTOPLASMOSIS BLASTOMYCOSIS CRYPTOCOCCUS PARASITIC SCHISTOSOMIASIS FOREIGN BODY SUTURE , ANY PROSTHESIS , VASCULAR GRAFT INORGANIC METALS,DUSTS SILICOSIS BERYLLOSIS UN KNOWN SARCOIDOSIS
  • 114. Epitheloid cells They are modified macrophages/ histiocytes which are somewhat elongated, having pale staining abundant cytoplasm, vesicular, lightly stained slipper shaped nucleus  Cell membrane of adjacent epitheloid cell is closely apposed due to hazy outline  They are weakly phagocytic
  • 115. GIANT CELLS  Formed by fusion of epitheloid cells  May have 20/more nuclei  Nuclei present centrally- FOREIGN BODY TYPE  Nuclei at periphery like horse shoe/ ring/clustered at two poles- LANGHANS TYPE  They are also weakly phagocytic  Produce secretory products which helps to remove invading agents
  • 116. NECROSIS  It is feature of some granulomatous conditions  E.g: caseation necrosis in TB FIBROSIS  Due to proliferation of fibroblasts at periphery of granuloma
  • 117. Factors favouring formation of granuloma 1. Presence of poorly digestible irritant 2. Presence of cell mediated immunity to irritant implying role of hypersensitivity in granulomatous inflammation Types of granuloma 1. FOREIGN BODY GRANULOMA : Material can be seen in center when viewed with polarised light 2. IMMUNE GRANULOMA : Due to microbes capable of activating cell mediated immunity
  • 119. LPS EXOGENOUS PYROGENS TNF,IL-1 ENDOGENOUS PYROGENS INCREASE CYCLOOXYGENASE PGE2 STIMULATE RELEASE OF CYCLIC AMP RESET TEMPERATURE SET POINT AT HIGHER LEVEL FEVER
  • 120. • Temperature > 40C • Triggers cold receptors Severe Inflammation • Pallor • A feeling of coldness of skin surface Reflex Vasoconstriction Of Vessels RIGOR Shaking Exaggerated shivering which occurs with a high fever
  • 121. Changes in pulse rate  Increase in temperature accompany increase in pulse  For every 1 degree F rise in temp pulse increase by 10beats/minute  Conversely bradycardia occurs in typhoid fever
  • 122. Acute phase proteins  Mostly synthesized in liver  Clinical concentration increase 100fold in inflammation  E.g: CRP, serum amyloid A protein(SAA), Fibrinogen  Cytokines upregulate their synthesis by stimulating hepatocytes  CRP, SAA acts as opsonins and fix complement
  • 123. They have beneficial effects in acute inflammation but in chronic prolonged production leads to secondary amyloidosis CRP  Levels increased in infection , inflammation  Tissue necrosis , malignancy , auto immune diseases  It binds to phosphocholine on dead / dying cells and activate complement  Enhances phagocytosis by microbes  Marked increase indicates risk for CVD , hypertension diabetes
  • 124. LEUKOCYTOSIS  Common feature of especially for bacterial infections  Count increase by 15,000 to 20,000cells/cumm  If it increase up to 1lakh – LEUKEMOID REACTION (but splenomegaly, lymphadenopathy, hemorrhages are absent) MYELOID LEUKEMOID TB, MENINGITIS ENDOCARDITIS BURNS MERCURY POISONING LYMPHOID LEUKEMOID INFECTIOUS MONONUCLEOSIS TB, PERTUSIS CHICKEN POX MEASLES
  • 125. INITIAL INCREASE ACCELERATED RELEASE OF CELLS DUE TO TNF, IL-1 INCREASE IMMATURE NEUTROPHILS IN BLOOD PROLONGED INFECTION INCREASED COLONY STIMULATING FACTORS INCREASED CELLS FOR COMPENSATION OF CELL LOSS LEUKOCYTOSIS
  • 126. NEUTROPHILIC LEUKOCYTOSIS BACTERIAL INFECTIONS, MI, BURNS EOSINOPHILIC LEUKOCYTOSIS PARASITIC INFESTATIONS, ASTHMA, ALLERGIES BASOPHILIC LEUKOCYTOSIS (RARE) INDICATIVE OF MYELOPROLIFERATIVE DISEASE (CML) MONOCYTOSIS (COMMON IN CHRONIC) TB, ENDOCARDITIS, COLLAGEN VASCULAR DISEASE(SLE), INFLAMMATORY BOWEL DISEASE(ULCERATIVE COLITIS) LYMPHOCYTOSIS TB, VIRAL(HEP-A, CMV, EBV)
  • 128. OVER PRODUCTION OF NO BY CYTOKINE ACTIVATED CARDIAC MYOCYTES HEART FAILURE DIC HEART FAILURE HYPOGLYCEMIA SEPTIC SHOCK
  • 129. LYMPHANGITIS- LYMPHADENITIS  Lymphatics and lymphnodes that drain the inflammed tissue show reactive inflammatory changes  This is a non specific reaction to mediators released from inflammed tissues  LYMPHANGITIS Inflammation Of Lymphatic Vessels And Channels  LYMPHADENITIS Inflammation of lymph node
  • 130. REGULATION OF INFLAMMATION 1. ACUTE PHASE PROTEINS Alpha 1 anti trypsin:  It Is a Protease Inhibitor  Protects Tissues From Enzymes Of Inflammatory Cells  Especially Neutrophil Elastase  In Absence Degradation Of Elastin  If This Occur In Lungs , This Leads To Respiratory Problems
  • 131.  Protease inhibitor  Hapatglobin  It Scavangers Hb Released Into Circulation  Potent Antioxidant  Resist Cell Oxidative Stress  Inhibits COX , LOX
  • 132. 2. CORTICOSTEROIDS  Endogenous glucocorticoids act as anti inflammatory agents  Their levels are increased in infection , trauma by self regulating mechanism 3. Supressor T cells / regulator T cells  Modulate immune system  Maintain tolerance to self antigens
  • 133. 4. Anti inflammatory chemical mediators propree RESOLVINS RvS OMEGA 3
  • 134. FACTORS DETERMINING VARIATIONS IN INFLAMMATORY RESPONSE
  • 135. FACTORS INVOLVING THE ORGANISM Type of injury and infection  Lung reacts to pneumococci by occurrence of pneumonia  While it responds to tubercle bacilli by granulomatous inflammation Dose  Concentration of organism in small dose form local lesions  Large dose cause severe spreading infections
  • 136. Portal Of Entry  Vibrio cholera is not pathogenic if injected sub cutaneously but cause cholera if swallowed Product Of Organisms  Certain products cause spread of infection  e.g : streptokinase by streptococci coagulase by staphylococci
  • 137. FACTORS INVOLVING THE HOST 1. AGE : very young, very old are less able to combat infection because of lack of inflammatory response Many elderly patients respond with a chronic inflammatory response which in young patients have provoked acute response 2. DAMAGE TO BONE MARROW AND RETICULO ENDOTHELIAL SYSTEM
  • 138. 3. ANTIBIOTIC THERAPY  Antibiotics decrease inflammation because clearing infection removes reason for inflammation  Inflammatory response is modified depending on how the agent respond to therapy
  • 139. 4. Diet  when you eat your body forms PG’s from nutrients in diet  This can be inflammatory / anti inflammatory  Imbalance in diet leads to formation of inflammatory PG  On other hand omega-3 fatty acids , antoxidants , phyto nutrients can produce anti inflammatory PG
  • 140. FOODS HIGH SATURATED FAT MEAT EGGS DAIRY PRODUCTS COFFEE CONTAINS CRP PROCESSED MEATS COOKING FOODS AT HIGH TEMP CAUSE RELEASE OF TOXINS TRANS FAT INTAKE OF PROCESSED FRIED FOODS HIGH GLYCEMIC INDEX CHO INSULIN CAUSE METABOLISM OF AA PRO INFLAMMATORY FOODS
  • 142. CONCLUSSION WAR AND INFLAMMATION  Both are stereotyped responses to outside threats  There are specialised troops(immune cells)  Supply routes(vessels)  Communication and intelligence(mediators)  Huge array of lethal weapons(enzymes) IN WAR AS IN INFLAMMATION THERE IS DAMAGE TO BOTH ENEMY AND FRIENDLY FORCES AND SEVERE DAMAGE TO BATTLE FIELD ITSELF
  • 143. PROBABLY YOUR OWN DEATH WILL BE CAUSED BY YOUR LAST INFLAMMATORY RESPONSE
  • 144. References 1. Robbins and Cotran Pathologic Basis of Disease 7th edition 2. Guyton and Hall Text Book of Medical Physiology 11th edition 3. Harsh Mohan Text Book of Pathology 5th edition PRESENTED BY ANUSHA.V PG-1ST YEAR

Notas del editor

  1. Enflammare……………latin word
  2. Dynamic process occuring in vascularised vaible tissues……..medico legal distinction between antemortem and postmortem tissues can be made by presence of infl …………
  3. Metchinkoff conducted exp on starfish larva……he implanted foreign material into larva and observed changes in blood cells…..blood cells surrounded foreign body…….from this simple observation he further prog to demonstration of phagocytosis
  4. Lewis named the mediator as h substance……….later it was discovered as histamine…………but antihistamine therapy did not interfere with triple response………indicating that there are substances other than histamine which are involved in infl
  5. LDH: marker of tissue break down Ldh abundant in rbc: marker of hemolysis: marker in mi( levels peak at 3to4 days n remain elevated upto 10 days Ldh cause conversion of pyruvate(end product of glycolysis) to lactate in absence of oxygen
  6. In medical infl…..any reaction which is less than 6weeks is acute………..which is greater than 6weeks is chronic In dental 10 to 12 days is acte………..beyond 12 is chronic
  7. C-cysteine residue…………so 2 cysteine residues seperated by an aminoacid……..
  8. Opsonins coat bacteria they act as signals
  9. When cells are acted upon by diverse stimuli…………they release certain substances……….which act as mediators
  10. Can men……large
  11. WHEN CELL MEMB PHOSPHOLIPIDS ARE PRODUCING ARACHIDONIC ACID………..PAF IS A BYPRODUCT
  12. KALLIKREIN IS A SERINE PROTEASE CAPABLE OF CLEAVING PEPTIDE BONDS
  13. CA—CALCIUM ; PL—PLATELET MEMBRANE PHOSPHOLIPID……. GENERALLY TISSUE FACTOR IS HIDDEN BY COLLAGEN IN BASEMENT MEMBRANE……DAMAGE CAUSE EXPOSURE OF TF
  14. FIBROSIS: IF INFL OCCURS IN TISSUES WHICH ARE NOT CAPABLE OF REGENERATION OR IF THERE IS MORE PUS WHICH CANNOT BE CLEARED BY INFL CELLS OR IF THERE IS MORE FIBRIN………IT INDUCE CONN.TISSUE FORMATION
  15. THE INABILITY OF AN PREVIOUSLY SENSITISED INDIVIDUAL TO EXPRESS DELAYED TYPE HYPERSENSITIVITY IS CALLED----ANERGY
  16. MOLECULAR MIMICRY: CERTAIN MICROBIAL PEPTIDES THEY RESEMBLE HOST PROTEINS……. BEST E.G IS AB’S AGAINST BETA HEMOLYTIC STEPTOCOCCI CROSS REACT WITH MYOCARDIAL PROTEINS
  17. B-LYMPHOCYTES –PRODUCED IN BURSA OF FABRISCIUS IN BIRDS EQUIVALENT IN MAMMALS IS- PEYERS PATCHES IN INTESTINE
  18. But one of law of war is once you enter battle field………..you should kill enemy………..no matter you like it or not……. Like that if body wants to b healthy it should fight against infections……………by eliciting inflammatory response………..