3. Inflammation and Repair

Question 1

Main components of inflammation

Answer 1

Vascular reaction and cellular response
both activated by mediators from plasma proteins and various cells

Question 2

5 steps of inflammatory response

Answer 2

Recognition of injurious agent
Recruitment of leukocytes
Removal of agent
Regulation of response
Resolution (repair)

Question 3

Causes of inflammation

Answer 3

infections, tissue necrosis, foreign bodies, trauma, immune response among others

Question 4

Outcome acute inflammation

Answer 4

Elimination of noxious stimulus followed by decline of reaction and repair of damaged tissue
Or persistent injury resulting in chronic inflammation

Question 5

Vascular reactions in acute inflammation

Answer 5

Vasodilation (by inflammatory mediators)
Increased vascular permeability
Lymphatic vessels and lymph nodes

Question 6

Increased vascular permeability

Answer 6

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

Question 7

Leukocyte recruitment

Answer 7

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

Question 8

Cytokines and neutrophils

Answer 8

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.

Question 9

Removal of offending agents

Answer 9

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)

Question 10

Prinsipal medioators of inflammation

Answer 10

Vasoactive amines, mainly histamine
Arachidonic acid metabolites
Cytokines
Complement proteins
Kinins

Question 11

Vasoactive amines

Answer 11

Mainly histamine
Vasodilation and increased vascular permeability

Question 12

Arachidonic acid metabolites

Answer 12

Prostaglandins and leukotrienes
Several forms, involved in vascular reactions, leukocyte chemotaxis and other reactions of inflammation
Antagonized by lipoxins

Question 13

Cytokines

Answer 13

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)

Question 14

Complement proteins

Answer 14

Activation of complement system by microbes or antibodies
Generation of multiple breakdown products
Responsible for leukocyte chemotaxis and other particles and cell killing

Question 15

Kinins

Answer 15

Produced by proteolytic cleavage of precurors
Mediate vascular reaction, pain.

Question 16

Chronic inflammation

Answer 16

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

Question 17

Granulomatous inflammation

Answer 17

morphologically specific pattern of chronic inflammation induced by T cell and macrophage activation in response to agent that is resistent to eradication

Question 18

System effects of inflammation

Answer 18

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

Question 19

Septic shock

Answer 19

Fall in blood pressure, disseminated intravascular coagulation, metabolic abnormalities, induced by high levels of TNF and other cytokines

Question 20

Repair by regeneration

Answer 20

Continuously dividing cells (depends on proliferative potential of constituent cells)
Cell proliferation (cell cycle)
(regeneration of liver by cytokines and growth factors)

Question 21

Scar formation

Answer 21

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)