Inflammation and Repair Flashcards
Inflammation is
a protective reaction of a living tissue to injury.
Eg. of delayed prolonged inflammatory reaction:
Sunburn
Inflammation steps: (5)
- recognition of the injurious agent
- recruitment of leukocytes
- removal of the agent
- regulation (control) of the response
- resolution (repair)
Acute inflammation had 2 majors components:
- Vascular change
2. Cellular events
Vascular change during Acute inflammation:
- Vasodilatation (increase blood flow)
- Increase vascular permeability (plasma proteins leave the circulation)
- Endothelial cell activated (increase adhesion and migration of leukocyte)
Cellular events during Acute inflammation:
- Emigration of the leukocytes from the circulation
- Cellular recruitment (accumulation in the focus of the injury)
- Activation of the leukocytes
Principal leukocytes in acute inflammation:
Neutrophils
When there is decrease osmotic pressure and increase hydrostatic pressure, the fluid leak out and is picked up by the lymphatics. This fluid is call:
Transudate (low proteins content, bc normally, capillaries are not permeable to proteins)
High protein fluid is call:
Exudate
Exudate (high protein fluid) change the balance of osmotic forces due to:
the increase of permeability when inflammation occurs, allows some proteins to escape on the venous side.
Recognition of Microbes, Necrotic cells and foreign substances (distinguish the danger from normal tissues) is done by
Receptor called ‘‘pattern recognition receptors’’ express on the surface of phagocytes, dendritic cells and epithelial cells.
2 most important families of Pattern recognition receptors are:
- Toll-like receptors (TLRs) located in plasma membranes and endosomes
- Inflammasome (detects products from death cells/bacteria)
The Increased vascular permeability is induced by
- Histamine, kinins and other mediators causing gaps between endothelial cells;
- By direct or leukocyte-induced endothelial injury;
- by increase passage of fluids through the endothelium
Endothelial cell contraction leading to intercellular gaps in postcapillary venules is due to:
- histamine, bradykinin and leukotrienes binding to endothelial cell.
- Cytokines (eg. Tumor necrosis factor - TNF) and inter-leukin-1 - IL-1 changing the cytoskeleton.
The sequence of events in the recruitment of leukocytes from the vascular lumen to the extravascular space consists of 4 steps:
- Margination and Rolling along the vessel wall
- Firm adhesion to the endothelium
- Transmigration between endothelial cells
- Migration in interstitial tissues toward a chemotactic stimulus.
WBCs float near the lumen wall doe to:
Laminar flow
RBCs float toward the middle of the lumen because:
they are smaller
During Step 1, Margination and Rolling steps of the recruitment of leukocytes, leukocytes come into contact with the endothelial cells of the capillary walls due to:
Chemoattractants cytokines –> Selectins and CAMs (cellular adhesion molecules) on the endothelial cell surface interact with ligands on the surface of leukocytes.
On the surface of most leukocytes, we can found:
- L-Selectin
2. Sialyl-Lewis X - modified proteins
During step 2, firm Adhesion to the endothelium is due to:
Integrins expressed on leukocytes cells surface interacting with their ligands on the endothelial cell causing adhesion. Increase their ability to bind by changing Integrin affinity and expression of integrin in the surface.
Integrins properties:
Normally expressed on leukocyte plasma membranes in a LOW-AFFINITY FORM and do not adhere until leukocyte are activated by chemotaxis.
'’Endothelial activation’’ during marginalization and rolling steps is due to
Cytokines
Cytokine-stimulated net result is:
Increase Integrin affinity and Increase Expression of integrin ligands to stable attachment of leukocytes to endothelial cells at sites of inflammation.
Transmigration step is due to:
Platelet endothelial cell adhesion molecule-1 (PECAM-1) or (CD31), mediates the binding events needed for leukocytes to traverse the endothelium.
After the leukocyte traverse the endothelium, getting through the vascular basement membrane is due to
Leukocytes secreting collagenases.
After extravasating from the blood, leukocytes move toward sites of infection or injury along a chemical gradient by a process called:
Chemotaxis (follow the concentration gradient from low to high concentration, where the concentration of chemokines is highest–> site of injury)
How is the bone marrow is involve during inflammation?
During inflammation, it requires a large immune response, your bone marrow will respond by making more of the immune cells.
Neutrophils caracteristics:
- Full of granules that contain lysosomal enzymes
- Fight microorganism very effectively due to these enzymes
- Phagocytose and release inflammatory mediators.
Monocyte/macrophage caracteristics:
- Phagocytose and release inflammatory mediators
- initiate the immune response
- Clean up the dead and injured cells/bacteria.
Eosinophils caracteristics:
-involve in reaction with parasites
