DR. ROOPAM JAIN COURSE DIRECTOR PROFESSOR & HEAD, DEPT. OF PATHOLOGY & BLOOD BANK

1. INFLAMMATION:
Lecture - 3
DR. ROOPAM JAIN
COURSE DIRECTOR
PROFESSOR & HEAD, DEPT. OF PATHOLOGY

2. II. Plasma Protein-derived
Mediators (Plasma Proteases)

3. • These include various products derived from activation
and interaction of 4 interlinked systems:
• kinin,
• clotting,
• Fibrinolytic
• complement.
• Each of these systems has its inhibitors and accelerators
in plasma with negative and positive feedback
mechanisms respectively.
• Hageman factor (factor XII) of clotting system plays a
key role in interactions of the four systems

4. The inter-relationship among 4 systems is
summarised

5. 1. THE KININ SYSTEM
• This system on activation by factor Xlla generates bradykinin
• Bradykinin acts in the early stage of inflammation & its effects
include:
• i) smooth muscle contraction;
• ii) vasodilatation;
• iii) increased vascular permeability
• iv) pain

6. Pathway of KININ SYSTEM

7. 2. THE CLOTTING
SYSTEM
• Factor Xlla initiates the cascade of the clotting system
resulting in formation of fibrinogen which is acted upon
by thrombinto form fibrin and fibrinopeptides.
• The actions of fibrinopeptides in inflammation are:
• i) increased vascular permeability;
• ii) chemotaxis for leucocyte; and
• iii) anticoagulant activity.

8. Pathway of the clotting system

9. 3. THE FIBRINOLYTIC
SYSTEM
• This system is activated by plasminogen activator, the
sources of which include kallikrein of the kinin system,
endothelial cells and leucocytes.

10. 4. THE COMPLEMENT
SYSTEM
• The actions of activated complement system in inflammation are
as under: ”
• C3a, C5a, C4a (anaphylatoxins) activate mast cells & basophils to
release of histamine, cause increased vascular permeability
causing oedema in tissues, augments phagocytosis. ”
• C3b is an opsonin. ”
• C5a is chemotactic for leucocytes. ”
• Membrane attack complex (MAC) (C5b-C9) is a lipid dissolving
agent and causes holes in the phospholipid membrane of the cell

11. REGULATIONOF INFLAMMATION
• i) Acute phase reactants
• ii) Glucosteroids
• iii) Free cytokine receptors
• iv) Anti-inflammatory chemical mediators - PGE2 or
prostacyclin have both pro-inflammatory as well as anti-
inflammatory actions.

12. THE INFLAMMATORY CELLS
• The cells participating in acute and chronic inflammation
are circulating leucocytes, plasma cells, tissue macrophages
and inflammatory giant cells.

13. Morphology and functions of inflammatory
cells.

14. Morphology and functions of inflammatory cells.

15. Morphology and functions of inflammatory cells.

16. MONONUCLEAR-PHAGOCYTE SYSTEM
(RETICULOENDOTHELIAL SYSTEM)
• A. Blood monocytes These comprise 4-8% of circulating leucocytes.
• B. Tissue macrophages These include the following cells in different tissues:
• i) Macrophages or phagocytes in inflammation.
• ii) Histiocytes which are macrophages present in connective tissues.
• iii) Epithelioid cells are modified macrophages seen in granulomatous
inflammation.
• iv) Kupffer cells are macrophages of the liver.
• v) Alveolar macrophages (type II pneumocytes) in the lungs.
• vi) Reticulum cells are macrophages/histiocytes of the bone marrow.
• vii) Tingible body macrophages of germinal centres of the lymph nodes.
• viii) Littoral cells of the splenic sinusoids.
• ix) Osteoclasts in the bones.
• x) Microglial cells of the brain.
• xi) Langerhans’ cells/dendritic histiocytes of the skin.
• xii) Hoffbauer cells of the placenta.
• xiii) Mesangial cells of the glomerulus.

17. Role of macrophages in
inflammation
• The functions of mononuclear-phagocyte cells are as under:
• i) Phagocytosis (cell eating) and pinocytosis (cell drinking).
• ii) Macrophages on activation by lymphokines released by T lymphocytes or by non-
immunologic stimuli elaborate a variety of biologically active substances as under:
• a) Proteases like collagenase and elastase which degrade collagen and elastic tissue.
• b) Plasminogen activator which activates the fibrinolytic system.
• c) Products of complement.
• d) Some coagulation factors (factor V and thromboplastin) which convert fibrinogen to
fibrin.
• e) Chemotactic agents for other leucocytes.
• f) Metabolites of arachidonic acid.
• g) Growth promoting factors for fibroblasts, blood vessels and granulocytes.
• h) Cytokines like interleukin-1 and TNF-a.
• i) Oxygen-derived free radicals.

18. GIANT CELLS
• A few examples of multinucleate giant cells exist in normal
tissues (e.g. osteoclasts in the bones, trophoblasts in
placenta, megakaryocytes in the bone marrow).
• in chronic inflammation when the macrophages fail to deal
with particles to be removed, they fuse together and form
multinucleated giant cells.
• morphologically distinct giant cells appear in some tumours
also.

19. A. Giant cells in inflammation:
A, Foreign body giant cell
B, Langhans’ giant cells
C, Touton giant cell with circular pattern of nuclei and vacuolated cytoplasm.

20. B. Giant cells in tumours:
D, Anaplastic tumour giant cell with nuclei of variable size and shape.
E, Reed-Sternberg cell.
F, Osteoclastic tumour giant cell.

21. ACUTE INFLAMMATION
FACTORS,
MORPHOLOGY,
EFFECTS,
FATE

28. • 99. An autopsy is performed on a 65-year-old man,
Suresh who died of congestive heart failure. Sections
of the liver reveal yellow-brown granules in the
cytoplasm of most of the hepatocytes. Which of the
following stains would be most useful to
demonstrate with positive staining that these
yellow-brown cytoplasmic granules are in fact
composed of hemosiderin (iron)?
• (a) Oil red O stain
• (b) Oil red O stain
• (c) Periodic acid- Schiff stain
• (d) Prussian blue stain
• (e) Sudan black B stain
• (f) Trichrome stain