Is a protective response The body’s response to injury Interwoven with the repair process

1. Inflammation &
Cellular responses

2. Inflammation
 Is a protective response
 The body’s response to injury
 Interwoven with the repair process

3. Inflammation
 Types
 Acute (sec, mins., hrs)
 Chronic (days, weeks, months, yrs)

4. Causes of inflammation
 Bacterial
 Viral
 Protozoal
 Metazoal*
 Fungal
 Immunological
 Tumours
 Chemicals, toxins etc
 Radiation
*A subdivision of the animal kingdom that includes all
multicellular animal organisms having cells that are
differentiated and form tissues and organs.

5. Acute inflammation
the initial response of the body to harmful stimuli,
achieved by the increased movement of plasma and
leukocytes (especially granulocytes) from the blood into
the injured tissues.
Inflammation is not a synonym for infection.

6. Inflammation
 The Cardinal Signs of Acute
Inflammation
RUBOR
CALOR
TUMOR
FUNCTIO LAESA

7. 1. calor - heat
2. rubor - redness
3. tumor - swelling
4. dolor - pain
5. functio laesa - loss (or
impairment) of function (Galen)

8. Cardinal signs of inflammation

9. 2nd Yr Pathology 2010
Cardinal signs of inflammation

10. 2nd Yr Pathology 2010
Cardinal signs of inflammation

11. 2nd Yr Pathology 2010
Cardinal signs of inflammation

12. 2nd Yr Pathology 2010
Cardinal signs of inflammation

13. 2nd Yr Pathology 2010
Cardinal signs of inflammation

14. Inflammation
The basis of the five cardinal signs
 Increased blood flow due to vascular dilatation gives
redness and heat.
 Increased vascular permeability gives oedema causing
tissue swelling.
 Certain chemical mediators stimulate sensory nerve
endings giving pain. Nerves are also stimulated by
stretching due to oedema.
 Pain and swelling result in loss of function.

15. Components of acute and chronic inflammation

16. Cell of the acute inflammatory
response
 Polymorphonuclear leukocyte

17. The process of inflammation

19. The phases of inflammation
 FIRST THERE IS VASCULAR DILATATION
followed by exudation of protein-rich oedema
fluid which floods the area, dilutes toxins, allows
immunoglobulins to opsonise bacteria and
provides substrate (fibrinogen) for fibrin
scaffold*.
 SECOND THERE IS ACTIVE EMIGRATION OF
POLYMORPHS through vessel wall and along the
chemotactic gradient to the site of injury
make (a foreign cell) more susceptible to phagocytosis
*a temporary or movable platform
the movement of a microorganism or cell in response to a chemical
stimulus.

20.  THE VASCULAR PHASE OF INFLAMMATION
Fluid escapes from vessels because of endothelial cell (EC)
retraction, opening up gap-junctions.
The vessels which are normally involved are the post-capillary
venules where the EC have high affinity receptors for histamine.
Severe EC injury leads to leakiness of all vessels capillaries,
venules and arterioles - giving acute local oedema,
e.g. blister formation after a burn.
The phases of inflammation

21. Local vascular manifestations of acute inflammation

22. Leukocyte migration in inflammation
V: a very small vein, especially one collecting blood from the capillaries
S: Cell adhesion molecules: selectins and integrins. ... Selectins comprise a family of
three members (E-, P-, and L-selectin) that are differentially expressed by leukocytes
and endothelial cells, and are involved in the early steps of leukocyte extravasation.
Integrins are the
principal receptors
used by animal cells to
bind to extracellular
matrix. They are
heterodimers
& function as
transmembrane linkers
b/w the extracellular
matrix and the actin
cytoskeleton.

23. Molecules modulating endothelial-neutrophil interactions
LFA-1 and MAC-1
(activated integrins)
Platelet/endothelia
l cell adhesion
molecule 1
(PECAM-
1, PECAM, CD31)

24. Acute inflammation: tissue effects
Pavementation and diapedesis
Leukocyte extravasation, less commonly called diapedesis, is the movement of
leukocytes out of the circulatory system and towards the site of tissue damage or
infection. This process forms part of the innate immune response, involving the
recruitment of non-specific leukocytes

25. Acute inflammation: tissue effects
Inflammatory cells in protein exudate

26. Acute inflammation: tissue effects
Blood vessel involved in the acute inflammatory process

27. Acute inflammation: tissue effects
Bronchopneumonia

28. Acute inflammation: tissue effects
Abscess: collection of acute inflammatory cells

29. Acute inflammation: tissue effects
Multiple splenic abscesses

30.  Vasoactive amines
 Histamine
 Serotonin (5-HT)
 Neuropeptides
 Substance P
 Plasma proteases and the complement system
 Action of Hageman factor
 Arachidonic acid metabolites
 Prostaglandins
 Leukotrienes
 Lipoxins
 Cytokines
 IL-1, TNF etc.
 Chemokines (CXC and CC)
 Nitric oxide and oxygen-derived free radicals
Chemical mediators of inflammation

31. Chemical mediators of inflammation
 PREFORMED
Histamine, Serotonin
 NEWLY SYNTHESISED
Prostaglandins
Leucotrienes
Platelet activating factor
Cytokines
Nitric oxide
 LOCAL AND SYSTEMIC*
*mechanisms by which local immune stimulation is transmitted to
the periphery, leading to systemic inflammation. We concentrate
on the role of three signalling molecules: interleukin-1,
interleukin-6, and tumour necrosis factor alpha. These cytokines
provide a direct link between local and systemic inflammation

32. Chemical mediators of inflammation
(local and systemic)

33. Plasma proteases
Kinins are polypeptides and cause vasodilation and smooth muscle contraction. These
structurally related polypeptides, such as bradykinin and kallidin are members of the
autacoid family. They act locally to induce vasodilation and contraction of smooth
Kinins: any of a
group of
substances
formed in body
tissue in
response to
injury.

34. The complement system

35. Arachidonic acid metabolites
HETE =
hydroxyeicosatetraen
oic acid
HPETE =
hydroperoxyeicosatet
raenoic acid

36. Arachidonic acid
Arachidonic acid; 506-32-1; Arachidonate; Immunocytophyte;
(5Z,8Z,11Z,14Z)-icosa-5,8,11,14-tetraenoic acid; (all-Z)-
5,8,11,14-Eicosatetraenoic acid
Molecular Formula: C20H32O2
Molecular Weight: 304.474 g/mol
Arachidonic Acid is an unsaturated, essential fatty acid. It is found in animal and human
fat as well as in the liver, brain, and glandular organs, and is a constituent of animal
phosphatides. It is formed by the synthesis from dietary linoleic acid and is a precursor
in the biosynthesis of prostaglandins, thromboxanes, and leukotrienes.(ChemID Plus)
The beneficial effects of Omega-3 fatty acids are believed to be due in part to selective alteration
of arachidonate metabolism that involves cyclooxygenase (COX) enzymes. (PMID: 23371504)
Here, 9-oxononanoic acid (9-ONA), one of the major products of peroxidized fatty acids, was
found to stimulate the activity of phospholipase A2 (PLA2), the key enzyme to
initiate arachidonate cascade and eicosanoid production.
(PMID: 23704812) Arachidonate lipoxygenase (ALOX) enzymes metabolize arachidonic acid to
generate potent inflammatory mediators and play an important role in inflammation-associated
diseases. (PMID: 23404351)

37. Cytokines (IL-1 and TNF)
Cytokines : any of a number of substances, such as interferon,
interleukin, and growth factors, which are secreted by certain cells
of the immune system and have an effect on other cells. They are
small secreted proteins released by cells have a specific effect on
the interactions and communications between cells.

38. Nitric oxide (NO)

39. Effects of mediators of inflammation
Vasodilation:
Prostaglandins, NO
Increased vascular permeability:
Histamine, serotonin, C3a, C5a, bradykinin,
Leukotrienes C4, D4, E4, platelet activating factor
Chemotaxis, leukocyte activation:
C5a, leukotriene B4, bacterial products, chemokines (IL-8)
Fever:
IL-1, IL-6, TNF, prostaglandins
Pain:
Prostaglandins, bradykinin
Tissue damage:
Neutrophil and macrophage lysosomal enzymes, oxygen metabolites
NO

40. Phagocytosis
Phagocytosis of bacteria by polymorphs

41. PHAGOCYTOSIS
Recognition and attachment
Foreign objects coated with opsonins IgG and C3b which attach to
receptors on polymorph surface.
Engulfment
Cell membrane fuses around an object: at the some time
lysosomes
empty into the vacuole, often before vacuole has time to seal - this
gives
rise to 'regurgitation during feeding' and enzymatic damage to
surrounding
tissue.
Killing or degradation
H2O2, hypohalous acid (HOC1) produced by myeloperoxidase and
superoxides kill bacteria. Lysozyme digests them.

43. Chronic inflammation

44. Cells of the chronic inflammatory
response
 Lymphocytes
 Monocytes/ macrophages
 Plasma cells

45. Maturation of circulating monocytes
to macrophages

46. Macrophage-lymphocyte interactions
in chronic inflammation

47. Cellular interactions in chronic
inflammation

48. Chronic inflammation: tissue
effects
Knee joint in rheumatoid arthritis

49. Chronic inflammation: tissue
effects
Chronic cervicitis

50. Chronic inflammation: tissue
effects
Lung abscess

51. Granulomatous
inflammation:
a special form of
chronic inflammation

52. Granuloma
 Definition
 A collection of macrophages, lymphocytes,
mononuclear cells and fibroblasts with or
without giant cell formation and constitutes
a special form of chronic inflammation

53. Granulomatous inflammation
Bacterial:
TB, Leprosy, Syphillis, cat-scratch disease
Parasitic:
Schistosomiasis
Fungal:
Histoplasma, blastomycosis, cryptococcus
Inorganics, metals, dusts:
Silicosis, berrylliosis
Foreign body
Unknown:
Sarcoidosis

54. Granulomatous inflammation:
tissue effects

55. Granulomatous inflammation:
tissue effects

56. Granulomatous inflammation:
tissue effects

57. Granulomatous inflammation:
tissue effects
Epithelioid cells

58. Granulomatous inflammation:
tissue effects
Talc granulomas in the lung

59. Healing and repair

60. Wound healing: critical steps

61. The cell cycle

62. Cyclins, cyclin dependent kinases and
cyclin dependent kinase inhibitors

63. Cell-cell interactions in repair

64. Cell surface receptors in healing
and repair

65. The major components of the
extracellular matrix (ECM) required for
healing and repair

66. Extracellular matrix re-modelling occurs by the action of
Matrix metalloproteinases

67. Matrix metalloproteinase
regulation

68. Critical steps in angiogenesis

69. Major growth factors in
wound healing

70. Wound healing: critical steps

71. Granulation tissue

72. Granulation tissue

73. Scar tissue
Skin

74. Scar tissue
Lung

75. Outcome of healing and repair

76. When healing goes wrong
Keloid scar