3. Inflammation and Repair Flashcards
Main components of inflammation
Vascular reaction and cellular response
both activated by mediators from plasma proteins and various cells
5 steps of inflammatory response
Recognition of injurious agent
Recruitment of leukocytes
Removal of agent
Regulation of response
Resolution (repair)
Causes of inflammation
infections, tissue necrosis, foreign bodies, trauma, immune response among others
Outcome acute inflammation
Elimination of noxious stimulus followed by decline of reaction and repair of damaged tissue
Or persistent injury resulting in chronic inflammation
Vascular reactions in acute inflammation
Vasodilation (by inflammatory mediators)
Increased vascular permeability
Lymphatic vessels and lymph nodes
Increased vascular permeability
Induced by histamine, kinins etc
produce gaps between endothelial cells by direct or leukocyte induced endothelial injury and increased passage of fluids through endothelium
Allows plasma proteins and leukocytes (mediator of host defense) to enter site
Fluid leak from blood vessels (exudation) results in edema
Leukocyte recruitment
From blood into tissue, migrate to site and activated
Loose attachment to and rolling on endothelium (by selectins), firm attachment to endothelium (by integrins) and migration through interendothial gaps
Cytokines and neutrophils
cytokines promote expression of selectins and integrin ligands on endothelium, increase avidity of integrins for their ligands (chemokines) and promote directional migration of leukocytes
Tissues responding to pathogens produce many cytokines
Neutrophils predominate in early inflammatory infiltrate and later replaced by monocytes and macrophages.
Removal of offending agents
Leukocyte phagocytosis (later phagolysosomes)
Destruction by free radicals (ROS, NO) generated in activated leukocyte and granule enzymes
Neutrophils extrude nucleir contant from extracellular nets that trap and destroy
Granule enzymes released into site
Anti-inflmmatory mediators terminate inflammatory reaction
(pathologic consequences of inflammation: normal tissues may be damaged)
Prinsipal medioators of inflammation
Vasoactive amines, mainly histamine
Arachidonic acid metabolites
Cytokines
Complement proteins
Kinins
Vasoactive amines
Mainly histamine
Vasodilation and increased vascular permeability
Arachidonic acid metabolites
Prostaglandins and leukotrienes
Several forms, involved in vascular reactions, leukocyte chemotaxis and other reactions of inflammation
Antagonized by lipoxins
Cytokines
Proteins produced by many cell types
Act at short range
Multiple effects: leukocyte recruitment and migration, acute inflammation (principal ones: TNF, IL-I and chemokines)
Complement proteins
Activation of complement system by microbes or antibodies
Generation of multiple breakdown products
Responsible for leukocyte chemotaxis and other particles and cell killing
Kinins
Produced by proteolytic cleavage of precurors
Mediate vascular reaction, pain.
Chronic inflammation
Prolonged host response
Cause: microbes that resist elimination, immune responses and some toxic substances
Characterized: coexisting inflammation, tissue injury, attempted repair by scarring and immune response
Mediated by: cytokines (produced by macrophages and (T) lymphocytes); birectional interactions between cells tend to amplify and prolong inflammatory reaction
Granulomatous inflammation
Granulomatous inflammation
morphologically specific pattern of chronic inflammation induced by T cell and macrophage activation in response to agent that is resistent to eradication
System effects of inflammation
Fever: cytokines (TNF, IL-1) stimulate production of PGs in hypothalamus
Production of acute phase proteins (C-reactive protein; synthesis stimulated by cytokines (IL-6)
Leukocytosis: cytokines (CSFs) simulate production of leukocytes in bone marrow
septic shock
Septic shock
Fall in blood pressure, disseminated intravascular coagulation, metabolic abnormalities, induced by high levels of TNF and other cytokines
Repair by regeneration
Continuously dividing cells (depends on proliferative potential of constituent cells)
Cell proliferation (cell cycle)
(regeneration of liver by cytokines and growth factors)
Scar formation
Deposition of connective tissue and scar formation
Clot formation, inflammation, angiogenesis and formation of granulation tissue, migration and proliferation of fibroblasts, collagen synthesis and connective tissue remodeling
Macrophages are critical by eliminating offending agents and producing cytokines and growth factors (for proliferation)
TFG-B: potent fibrogenic agent; ECM deposition depends on balance among fibrogenic agents, matrix metalloproteinases (MMPs) that digest EC< and tissue inhibitors of MMPs (TIMPs)
