Inflammation Flashcards
4 Cardinal signs of inflammation
redness
swelling
heat
pain
Acute Inflammation
-measure in hours or days
3 Major components of acute inflammation
Dilation of small vessels leading to increased blood flow (redness and heat)
Increased vascular permeability enabling plasma proteins and leukocytes to leave the blood stream (swelling)
Accumulation of leukocytes at site of infection/injury, leukocyte activation and elimination of pathogen
Potential outcomes of acute inflammation
resolution of infection
abscess formation
scarring
chronic inflammation
Chronic Inflammation
prolonged response (weeks or months) in which inflammation, tissue injury and attempts at repair coexist
Mediators of vasodilation
prostaglandins, nitric oxide, histamine
Mediators of increased bascular permeability
histamine, bradykinin, leukotrienes, PAF
Mediators of chemotaxis, leukocyte recruitment and activation
TNF, IL-1, Chemokine (C3a and C5a), Leukotrine B4, bacterial products (PAMPs)
Mediators of fever
IL-1, TNF, prostaglandins
Mediators of pain
prostaglandins, bradykinin
Mediators of tissue damage
lysosomal enzymes of leukocytes, reactive oxygen species, nitric oxide
Histamine
vasoactive amine that is preformed and stored in mast cell granules, released immediately following mast cell activation
principle mediator of vascular permeability
stimulates release of NO which causes vasodilation
Prostaglandin D2
lipid mediator of inflammation
Bradykinin
released because of activation of hageman factor (Factor XII)
increased vascular permeability and causes contraction of smooth muscle, dilation of blood vessels, and pain when injected into skin
Proinflammatory cytokines
major ones are: TNGalpha, IL-1, and IL6
upregulate adhesion molecules.
Chemokines
generated because of introduction of pathogen
C5a and C3a promote leukocyte migration to site of infection
Lysosomal enzymes, ROS, and NO
released from activated leukocytes
toxic to microbe
also damages host tissue
Steps of leukocyte extravasation
1) rolling or tethering via selectins and selectin ligands
2) leukocyte activation via chemokines
3) tight adhesion vis integrins and integrin ligands
4) transendothelial migration
5) migration along a chemokine gradient
Fever
produced in response to pyrogens
advantages: immune system functions more effectively at higher than normal body temp, host cells are some what protected from the deleterious effects of tumor necrosis factor-alpha at high temps, pathogens grown more poorly
inhibitors of cyclooxygenase such as aspirin, block prostaglandin E2 synthesis, therefore reducing fecer
Neutrophil rolling
histamine generation upregulates endothelial cell p-selectin
p-selectin binds to neutrophil p-selectin glycolipid (PSGL-1) which is constitutively expressed
interaction between P-selectin and PSGL-1 slows the neutrophil in a low affinity interaction
Neutrophil binding
ICAM-1 is upregulated on endothelial surface
LFA-1 binds to ICAM-1 and causes neutrophil to stop rolling in a high affinity interaction
Tranedothelial migration
Neutrophils and endothelial cells constitutively express CD31 (PECAM-1)
PECAM-1 is concentrated at intracellular junctions
Neutrophils squuze between the endothelial cells, then penetrate the basement membrane using surface expressed matrix metalloproteinases
PMNs are induced to migrate toward the site of inflammation by chemotactic substances
function of PMNs
phagocytose extracellular bacteria to prevent spread
release toxic substances that damage host tissue and inflammation
Monocyte extravasation
PMN’s predominate in early inflammatory infiltration and are later replaced by macrophages
Peaks after about 2 days
Macrophages have anti-microbial activity and anti-inflammatory/pro-resolving activity
M1
Classical activated pro-inflammatory macrophage
produce proinflammatory cytokines, ROS and NO
M2
alternatively activated pro-resolving macrophage
produce anti-inflammatory cytokines such as IL-10 and TGF beta
Wound Healing
initiated by TGF beta by inducing migration of fibroblasts to the site
Also stimulated secretion of collagen
Neutrophilia
increased peripheral blood neutrophils
often accompanies acute inflammation
IL-1 and TNF cause an accelerated release of PMNs from bone marrow
sustained release by macrophage and t lymphocyte-derived release of granulocyte colony stimulating factor
Acute phase response
may occur during systemic inflammation as a result of macrophage derived IL-6
increased plasma level of acute phase proteins causes accelerated erythrocyte sedimentation rate
Shock
high level of TNG
Delerterious effects of TNF in bloodstream
systemic vasodilaition with vascular permeability and consequent intravascular volume loss leads to hypotension and shock
systemic activation of coagulation system causes multisystem organ failure and serious bleeding
