Final terms Flashcards
Mediators of vasodilation
PGE2, histamine, NO
mediators of vascular permeability
histamine, C3a, C5a, bradykinin, leukotrienes C4, D4, E4, PAF
mediators of chemotaxis/activation
chemokines, C5a, LTB4, microbial products, fibrinopeptides
mediators of fever
IL-1,TNF-a, PGE2
mediators of pain
bradykinin, PGE2
mediators of tissue damange
lysosomal enzymes, oxygen radicals
Kinins
SOURCE: Hageman factor (XII) activates prekallikrein to kallikrein, kallikrein cleaves high molecular weight kinogen to bradykinin
ACTIONS: vasodilation, increased vascular permeability, pain, smooth muscle contraction
Complement fragments
ACTIONS:
C5a - chemotaxis for neutrophils, mast cell degranulation, increased vascular permeability, activates neutrophils and monocytes (oxygen radicals, leukotrienes, prostaglandins)
C3a - increased vascular permeability
vasoactive amines
histamine and serotonin
SOURCE: mast cells, basophils (platelets)
ACTION: vasodilation, increased venular permeability, bronchial and other smooth muscle contraction
Prostaglandins
SOURCE: arachidonic acid -> cyclooxygenase -> prostaglandins
ACTION: PGE2 mediates fever and pain
PGD2 mediates smooth muscle contraction in some tissue
Leukotriene B4
SOURCE: neutrophils, macrophages, eosinophils
ACTION: chemotaxis of neutrophils and eosinophils, chemokinesis of macs
Leukotrienes C4,D4, E4
SOURCE: neutrophils, macrophages, eosinophils
ACTION: increase vascular permeability, smooth muscle contraction
Lipoxin A4 and B4
SOURCE: transcellular biosynthesis by neutrophils and platelets
ACTION: inhibit leukocyte adhesion and chemotaxis
IFN - gamma
SOURCE: T-cells, NK cells
STIMULI: antigen early immune response
ACTION: upregulate macrophage function
= increase superoxide production/killing capacity,
= induce IL-12 and Th1 shifted immune response,
= upregulate class 2 MHC (increase antigen presentation),
= upregulate other growth factors (PDGF, TGF-a),
= chronic stimulation can lead to mac fusion (giant cell formation)
TNF-alpha in inflammation
SOURCE: macrophages, fibroblasts, others
STIMULI: endotoxin, bacteria, virus, protozoa, toxins
ACTION: endothelial cells= upregulate E-selectins and increase thrombogenicity
macrophages= enhance IL-1, IL-6, IL-8, IL-10, NO; induce acute phase reaction proteins; induce fibroblast proliferation and collagen synthesis; endogenous pyrogen; induce cachexia by suppression of appetite and lipoprotein lipase inhibition (IL-1 augments effects); induce apoptosis in selected cells
chemokines
SOURCE: macrophages, stromal cells, epithelial cells
STIMULI: virus, bacteria, toxins, protozoa, cytokines
ACTION:
CXC = many are chemotactic for neutrophils and endothelial cells (IL-8 for neuts)
CC = chemotactic for lymphocytes, monocytes, and eosinophils
Factors involved in fibroblast migration/replication and collagen synthesis
PDGF, EGF, FGF, TGF-B, TNF-a, IL-1
Factors involved in epithelial proliferation/migration
EGF, HGF, KGF
Factors involved in Angiogenesis
VEGF, FGF, PDGF
EGF-a (epithelial growth factor)
SOURCE: platelets and macrophages REPAIR EFFECT: increase keratinocyte and fibroblast proliferation increase keratinocyte migration increase granulation tissue formation
HGF (hepatocyte growth factor or scatter factor)
SOURCE: fibroblasts, platelets, endothelial cells
REPAIR EFFECT:
increase epithelial proliferation
increase cell scattering and migration in development
KGF (keratinocyte growth factor)
SOURCE: fibroblast
REPAIR EFFECT:
increase keratinocyte (epithelial cell) migration, proliferation, and differentiation
PDGF (platelet derived growth factor)
SOURCE: platelets, macrophages, endothelial cells, keratinocytes, smooth muscle cells
REPAIR EFFECT:
increase chemotaxis-neuts, macs, fibroblasts, SM cells
increase mitogenesis-fibroblasts, endothelial cells, SM cells
increase synthesis-MMPs (matrix metalloproteinases), fibronectin, hyaluronic acid
increase angiogenesis
increase wound contraction
TNF-alpha in tissue repair
SOURCE: macrophages, mast cells, and T-lymphocytes REPAIR EFFECT: activates macrophages increases fibroblast proliferation increases synthesis of collagen
