ACUTE INFLAMMATION

Vascular Changes , External manifestation of acute inflammation , CARDINAL SIGNS.
Chemotaxis , Steps of Mechanism, features of acute and chronic inflammation
Opsonization, Vascular and cellular events of acute inflammation , CHANGE IN VASCULAR FLOW AND CALIBER , OUTCOMES OF VASCULAR CHANGES ,
Phagocytosis , CHEMOTAXIS OF�LEUKOCYTES ,OPSONINS , SEQUENTIAL STEPS of phagocytosis , Receptors, Engulfment, Killing and degeneration, Reactive Oxygen Species[ROS] , Reactive Nitrogen Species , Granules Enzymes & other proteins , Fate of Acute Inflammation

1. Topics to present ACUTE INFLAMMATION Vascular Changes Chemotaxis Opsonization Phagocytosis

2. INFLAMMATION Definition Inflammation is a response of vascularized(vascular) tissues to infections and tissue damage that brings cells and molecules of host defense from circulation to sites where they are needed, to eliminate the offending agents. Note Inflammation is not harmful but it’s a natural, protective response. But in some cases; excessive, defective or misdirected inflammation results in complexities.

3. External manifestation The external manifestations of inflammation (acute) are called CARDINAL SIGNS .

4. Working Agents Steps of Mechanism Recognition of injurious agent Recruitment of Leukocytes Removal of agents Response regulation(control) Resolution[Repair]

5. Types There may be two types of inflammation: Acute Inflammation (Initial, rapid response to infections or tissue damage) Chronic Inflammation (Prolonged response in which tissue injury, inflammation and repair coexist in varying form)

6. ACUTE INFLAMMATION Events of Mechanism

7. Vascular and cellular events of acute inflammation

8. VASCULAR CHANGES CHANGE IN VASCULAR FLOW AND CALIBER VASODILATION is induced by inflammatory mediators e.g. histamine. Before vasodilation, there is a transient Vasoconstriction. Former involves arterioles and new capillary beds. It increases the blood flow at inflammation site. This is the cause of Heat and Redness[Erythema]

9. INCREASED VASCULAR PERMIBILITY (VASCULAR LEAKAGE) Vasodilation is quickly followed by INCREASED PERMIBILITY . RETRACTION OF ENDOTHELIAL CELLS results in the opening of inter-endothelial spaces which increase permeability. ENDOTHELIAL INJURY results endothelial necrosis which further increase it. This leaks the fluid, plasma proteins & leukocytes out.

10. This escape from vascular system to interstitium is known as EXUDATION. Extracellular fluid may be: EXUDATE has high protein content and cellular debris. TRANSUDATE has low protein content, cellular debris & specific gravity.

11. OUTCOMES OF VASCULAR CHANGES ADVANTAGES Maximize the movement of leukocytes from circulation to the site of infection & injury.

12. CHEMOTAXIS Definition The locomotion of cells (leukocytes) along the chemical gradient is called CHEMOTAXIS. How Gradient forms? It forms by both exogenous and endogenous substances acting as CHEMOATTRACTANTS i.e. Cytokines[chemokines & TNF] Bacterial Products Complementary system’s components(C5a) Leukotriene B4 (LBT 4) They are produced by microbes or host cells responding injury or infection during immunological reactions.

13. Mechanism After exiting the circulation, leukocytes reach the action site as, Chemo-attractants bind with the receptor site at leukocyte. They roll(selectins), attach firmly( integrins ) on epithelium & migrate through inter-epithelial gaps. Signaling occurs calcium mobilizes, assembly of cytoskeletal contractile elements. At leading edge, actin polymerizes & myosin localizes at back. By this leukocytes moves by extending filopodia at back.

14. Fig. CHEMOTAXIS OF LEUKOCYTES

15. Features The nature of leukocytes infiltrate, in chemotaxis, varies with: Age of inflammatory response Type of stimulus e.g.(in most cases) during first 6-24 hours, Neutrophils predominate & over 24-48 hours, monocyte-derived macrophages dominate as inflammatory infiltrate. Neutrophils plays great role as they are more in number, respond to chemokines more rapidly & attach more firmly. Former have less life span in tissues while macrophages do proliferate.

16. OPSONIZATION Definition The process of making the microbe or damaged-tissue cells more vulnerable to phagocytes to engulf. OR An immunological response to destroy pathogens by immune cells.

17. OPSONINS Definition An antibody or specific protein that binds to foreign microbe or damaged cells to make them more susceptible to phagocytosis. Example Immunoglobulin G [IgG] Complementary protein C3b iC3b (cleavage product of C3b)

18. Mechanism Opsonins are attached to the epitope. Form a protein coating around it. Phagocytes bear cell surface receptors for these complements fragments & express high affinity for them.

19. Advantages

20. PHAGOCYTOSIS Definition Phagocytosis is the process of engulfing the microbes or cellular debris at site of infection or injury.

21. PHAGOCYTES Definition Phagocytes are the cells which perform phagocytosis. Example e.g. Neutrophils Macrophages

22. SEQUENTIAL STEPS

23. Mechanism Recognition by phagocytic receptors Phagocytes have Mannose, Scavenger & opsins’ receptors. Which recognize the chemical substances just present in microbial cell wall not that of host. Opsonized microbial cell wall enhanced phagocytic activity.

24. Receptors

25. Engulfment A fter binding receptors with particles, cytoplasmic extension(Pseudopodia) flow around it. Plasma membrane pinches off to form cytosolic vesicle (Phagosome) Fusion of phagosome with lysosome. Discharge of lysosomal contents. During this normal cells may damage due to granular release.

26. Killing and degeneration Elimination of dead cell debris and microbes. Occurs in Lysosomes or Phagolysosomes. Accomplished by three ways i.e.

27. Reactive Oxygen Species[ROS] Assembly & activation of a multicomponent enzyme PHAGOCYTE OXIDASE [ NADPH oxidase],oxidizes NADPH. Oxygen reduces to Superoxide anion. This oxidation reaction , in neutrophils, is tightly packed with phagocytosis known as “RESPIRATORY BURST”. Superoxide dismutate to Hydrogen Peroxide but its not able to kill microbe thus converted to HOCl by Superoxide dismutase & Myeloperoxidase(MPO) respectively. Hydroxyl radical is also a powerful destructive agent. ROS are produced in phagolysosomes where they ingest particles.

28. Reactive Nitrogen Species Nitric oxide (NO) is a soluble gas produced by arginine by action of nitric oxide synthase (NOS) There are 3 types of NOS: iNOS kills microbes. NO reacts with superoxide radical forming highly reactive free radical Peroxynitrate . Like ROS , NO highly reactive free radicals damage lipids protein and nucleic acid of microbes of host cell.

29. Granules Enzymes & other proteins Neutrophils and monocytes have granules packed with enzymes and antimicrobial proteins. They degrades microbes ,dead tissues and may damage tissue. There are 2 types of granules: Phagocytic vesicle fused with lysosomal granules also engulf materials.

30. Fate of Acute Inflammation