11. HEAT REDNESS SWELLING PAIN LOSS OF
5 Cardinal Signs of Inflammation5 Cardinal Signs of Inflammation
12. 4 cardinal clinical signs of inflammation4 cardinal clinical signs of inflammation
described by Celsus, 1 A.D.:described by Celsus, 1 A.D.:
• Rubor - redness
• Tumor - swelling
• Calor - heat
• Dolor - pain
• Virchow added a fifth--loss of
function(functio laesa)
13. Steps Of Inflammatory ResponseSteps Of Inflammatory Response
• Remembered as five Rs:
• (1) Recognition of injurious agent
• (2) Recruitment of leukocytes
• (3) Removal of agent
• (4) Regulation of response
• (5) Resolution (repair).
33. ROLLINGROLLING::
Leukocytes tumble on endothelial
surface, transiently sticking along
the way
• Mediated by SELECTIN family of
adhesion molecules
• 3 members of this family
34. SELECTINSSELECTINS
• E-selectin (CD62E) on EC
• P-selectin (CD62P) EC & platelets
• L-selectin (CD62L) leukocytes
• Selectins bind sialylated
oligosaccharides ( sialyl-Lewis X
on leukocytes)
36. ADHESION & TRANSMIGRATIONADHESION & TRANSMIGRATION
• Adhesion mediated by integrins
• Activated by chemokines
• TNF and IL-1 activate EC to ↑
expression of ligands for integrins
41. DIAPEDESISDIAPEDESIS
• Leukocytes migrate thr’u vessel wall by
squeezing between cells at IC junctions
• Mediated by PECAM-1 (platelet
endothelial cell adhesion molecule 1
(CD31) on leukocytes & EC
42. CHEMOTAXISCHEMOTAXIS
• Leukocytes migrate toward sites of
infection or injury along a chemical
gradient
• Chemotactic substances
(1) bacterial products (2) cytokines
(3) C5a (4) LTB4.
46. PHAGOCYTOSISPHAGOCYTOSIS
• 3 steps
• (1) recognition and attachment of
particle to ingesting leukocyte
• (2) engulfment & formation of
phagocytic vacuole
• (3) killing and degradation of ingested
material.
47.
48. (1)(1) Recognition & attachment ofRecognition & attachment of
particle to ingesting leukocyteparticle to ingesting leukocyte
• Opsonins : host proteins that coat
microbes and target them for
phagocytosis (opsonization).
• Leukocytes express receptors for
opsonins
56. 3.Killing and Degradation of Microbes3.Killing and Degradation of Microbes
• Important microbicidal substances :
reactive oxygen species (ROS) and
lysosomal enzymes
• ROS
• HOCl• (hypochlorous radical)
•Superoxide radicals
(superoxide,H2O2, and OH•).
• Reactive nitrogen species( NO)
58. Defects in Leukocyte FunctionDefects in Leukocyte Function
• Common causes
• BM suppression ( tumors CT,RT)- ↓
leukocyte no.
• Diabetes - abnormal leukocyte
function
59. Defects in leukocyte function:Defects in leukocyte function:
• Margination and adhesion
–Etoh, steroids, AR leukocyte adhesion
deficiency
• Emigration toward a chemotactic stimulus
–drugs
–chemotaxis inhibitors
• Phagocytosis
–Chronic granulomatous disease
(CGD) :phagocyte oxidase generating ROS
60. Defects in leukocyte function:Defects in leukocyte function:
• Myeloperoxidase (MPO) deficiency:
Absent MPO-H2O2 system
• Chédiak-Higashi syndrome :impair
fusion of lysosomes with phagosomes
61. ACUTE INFLAMMATION - THREEACUTE INFLAMMATION - THREE
OUTCOMESOUTCOMES
• Resolution
• Progression to chronic inflammation
• Abscess
• Scarring or fibrosis
69. ABSCESSESABSCESSES
• Focal collections of pus
• Central, large necrotic region
rimmed by neutrophils
(surrounded by vessels and
fibroblastic proliferation )
72. ULCERULCER
• Local defect / excavation, surface of an
organ/ tissue prod. by necrosis of cells
& sloughing of inflammatory necrotic
tissue
• Sites (1)mucosa of GIT( Peptic ulcer),
GUT
• (2) Lower extremities, older persons
with circulatory distur.
95. CHEMOKINESCHEMOKINES
• 2 functions : leukocyte recruitment in
inflam. & N anatomic organization of cells
in lymphoid and other tissues
• Four groups
• Two major groups
• CXC :IL-8
• CC chemokines:MCP-1 , MIP-1α,
RANTES (regulated on activation normal
T expressed and secreted) and eotaxin .
96. Reactive Oxygen Species (ROSReactive Oxygen Species (ROS
• Synthesized via NADPH oxidase
(phagocyte oxidase) pathway
• Action (1) endothelial damage, with
thrombosis & ↑ perm.
• (2) protease activation and
antiprotease inactivation
• (3) direct injury to other cells
• Catalase, SOD, glutathione -↓ toxicity
97. NONO
• Synthesized from l-arginine, molecular
O2, NADPH by enzyme NOS.
• 3 isoforms of NOS
• Type I (nNOS)
• Type II (iNOS) present in macrophages
& EC induced by IL-1, TNF,IFN-γ,
bacterial endotoxin
• Type III (eNOS)
102. NeuropeptidesNeuropeptides
• Small proteins, such as substance P
• Transmit pain signals
• Regulate vessel tone
• Modulate vascular permeability
• Lung and GIT- Nerve fibers secrete NP
106. Critical steps : activation of C3Critical steps : activation of C3
• (1) Classical pathway : fixation of C1
to antig-antib complexes
• (2) Alternative pathway: bacterial
polysaccharides / microbial cell-wall
components, involve properdin and
factors B , D
• (3) Lectin pathway: plasma lectin
binds mannose residues on microbes
, activates early component of CP
107. ComplementComplement
• 3 pathways form C3 convertase :cleaves
C3 to C3a and C3b
• C3b deposits on cell or microbial surface
• Binds to C3 convertase complex to form
C5 convertase
• C5 convertase cleaves C5 → C5a & C5b
• Initiate final stages of assembly of C6 to
C9
• Thrombin : cleave C5
108.
109. ComplementComplement
• 1.Anaphylatoxins: C3a and C5a
↑vascular perm. and vasodilation ,induce
mast cells to release histamine.
• 2.C5a: activates lipoxygenase pathway
• 3.Leukocyte activation, adhesion, and
chemotaxis. C5a
• 4.Phagocytosis: C3b & iC3b act as
opsonins
• 5.Lysis of microbes - MAC
110. Coagulation and Kinin SystemsCoagulation and Kinin Systems
• 4 systems activated by Hageman
factor (factor XIIa)
• (1) Kinin system
• (2) Clotting system
• (3) Fibrinolytic system
• 4) Complement system.
118. Role of Mediators in DifferentRole of Mediators in Different
Reactions of InflammationReactions of Inflammation
• 1.Vasodilation:
Prostaglandins, Nitric oxide Histamine
• 2.↑ vascular perm:
Histamine and serotonin
C3a and C5a
Bradykinin
Leukotrienes C4, D4, E4
PAF
Substance P
119. Mediators in InflammationMediators in Inflammation
• 3. Leukocyte recruitment and
activation
TNF, IL-1
Chemokines
C3a, C5a
Leukotriene B4
Bacterial products, e.g., N-formyl
methyl peptides
135. Diseases with GranulomatousDiseases with Granulomatous
InflammationInflammation
• Tuberculosis :M. tuberculosis
• Noncaseating tubercle : a focus of
epithelioid cells, rimmed by fibroblasts,
lymphocytes, histiocytes, occasional
giant cells
• Caseating tubercle: central amorphous
granular debris, loss of all cellular detail;
acid-fast bacilli
151. 2.Acute-phase proteins2.Acute-phase proteins
• 2.Synthesized in liver
• Up-regulated by IL-6
• I) CRP II) Fibrinogen III)Serum amyloid A
(SAA) protein.
• Fibrinogen cause rouleaux- ↑ ESR
• CRP: ↑ risk of MI or stroke in pts. with
atherosclerotic vascular disease
152. 3. Leukocytosis
• TNF & IL-1-release cells from BM .
Shift to left
• CSFs - ↑ output of leukocytes from BM
• Neutrophilia , lymphocytosis ,
eosinophilia , leukopenia
153. Other manifestationsOther manifestations
• ↑ heart rate and BP
• ↓ sweating
• Rigors (shivering)
• Chills
• Anorexia, somnolence & malaise:
cytokines on brain cells
• Chronic inflammation: wasting syndrome
called cachexia, TNF- mediated appetite
suppression & mobilization of fat stores
156. 1.A 65-year-old woman had fever the past day.
On physical examination her temperature is 39 C
and blood pressure 90/50 mm Hg with heart rate
of 106/minute. A blood culture is positive for
Escherichia coli. Her central line pressure falls
markedly. She goes into hypovolemic shock as a
result of the widespread inappropriate release of a
chemical mediator derived from macrophages.
Which of the following mediators is most likely to
produce these findings?
A Nitric oxide
B Bradykinin
C Histamine
D Prostacyclin
E Complement C3a
157. 2.The major difference between a
transudate and an exudate is
(A) transudate has proteins whereas
exudate is essentially devoid of proteins
(B) both these are only seen during acute
inflammatory processes
(C) both are associated with a Suppurative
or Purulent inflammatory process
(D) transudate is associated with serous
inflammation whereas exudate is
associated with fibrinous inflammation
158. 3.Granulomatous Inflammation is
associated with which of the following
a. distinct acute inflammatory
process
b. distinct chronic inflammatory
process
c. persistent B-cell response to
certain microbes
d. IgM mediated response
159. 4.Which of the following is/are considered
an anaphylatoxins(s)
(A) lipoxins
(B) leukotrines
(C) C3a
(D) IL-1 and TNF
160. 5.What is the most common form of
increased vascular permeability
associated with acute inflammation
(A) direct endothelial injury
(B) endothelial cell retraction
(C) endothelial cell contraction
(D) leukocyte-dependent endothelial
damage
161. 6.Endothelial cell contraction &
retraction occur in
a) Postcapillary venules
b) Capillaries
c) Arterioles
d) All of the above