Flashcards in Fiber Chaper 13. INFLAMMATION AND CYTOKINES Deck (58)
Three phases of inflammation
1. Injury: causes exposed collagen, PAF and TF release
2. Platelets bind collagen: release growth factors (platelet derived growth factor PDGF) and leads to PMN and macrophage recruitment
3. Macrophages: dominant role in wound healing; release important growth factors (PDGF) and cytokines (IL-1 and TNF-a)
-chemotactic and activated inflammatory cells (PMHs and macrophages) and fibroblasts, which leads to collagen and ECM proteins
-chemotactic for smooth muscle cells
-has been shown to accelerate wound healing
epidermal growth factor
-chemotactic and activates fibroblasts
fibroblastic growth factor
-chemotactic and activates fibroblasts, which leads to collagen and ECM proteins
platelet activating factor
-is not stored, generated by phospholipase in endothelium, is a phospholipid
-chemotactic for inflammatory cells; increases adhesion molecules
For inflammatory cells: PDGF, IL-8, LTB-4, C5a, C3a, PAF
For fibroblasts: PDGF, EGF, FGF
PDGF, EGF, FGF, IL-8, hypoxia
PDGF, EGF, FGF
PMNs last how long?
1-2 days in tissues, 7 days in blood
Platelets last how long?
Lymphocytes do what?
Chronic inflammation (T cells) and antibody productions (B cells)
Type 1 Hypersensitivity (allergic reactions)
-Eosinophils: IgE receptors that bind to allergen, release major basic protein, which stimulates basophils and mast cells to release histamine; increased in parasitic infections
-Basophils: main source of histamine in blood; not found in tissue
-Mast cells: primary cell in type 1 hypersensitivity reactions; main source of histamine in tissues
-Histamine: vasodilation, tissue edema, postcapillary leakage; primary effector in type 1 hypersensitivity reactions
-Bradykinin: peripheral vasodilation, increased permeability, pain, pulmonary vasoconstriction (inactivated by ACE)
What is the main source of histamine in blood? Tissues?
Tissue: mast cells
What does histamine do?
-Released by basophils (in blood) and mast cells (in tissue) in response to major basic protein released by eosinophils (which have IgE receptos which bind allergen)
-Vasodilation, tissue edema, postcapillary leakage
What causes peripheral vasodilation, increased permeability, pain, and pulmonary vasoconstriction in a type 1 hypersensitivity reaction?
What inactivates bradykinin?
ACE; located in lung
also called endothelium derived relaxing factor
arginine -> (via NOS) -> nitric oxide
NO activates guanylate cyclase and increases cGMP resulting in vascular smooth muscle dilation
What is the precursor to nitric oxide?
What does NO do?
activated guanylate cyclase and increases cGMP to cause vascular smooth muscle dilation
What does the opposite of NO?
Endothelin (causes vascular smooth muscle constriction)
Main initial cytokine response to injury and infection
TNF-alpha and IL-1 release
-Macrophages are largest producers of TNF-a
-Increases adhesion molecules
-Cachexia in cancer patients
-Activates neutrophils and macrophages -> more cytokine production and cell recruitment
-High concentrations can cause circulatory collapse and multisystem organ failure
-Macrophages are main source
-Effects similar to TNF-a and synergized TNF-a
-Responsible for fever (PGE2 mediated in hypothalamus): raises thermal set point, NSAIDs can decrease fever by reducing PGE2 synthethis
-Alveolar macrophages: cause fever with atelectasis by releasing IL-1
What cytokine causes fever?
What cytokine causes cachexia?
Increases hepatic acute phase proteins (CRP and amyloid A)
What are interferons?
Released by lymphocytes in response to viral infection or other stimulants
-Activate macrophages, natural killer cells, and cytotoxic T cells
-Inhibit viral replication
Hepatic acute phase response proteins
-IL-6: most potent stimulus
-CRP: opsonin, activates complement
-Amyloid A and P
-(albumin, pre-albumin, and transferrin are DECREASED)
Cell adhesion molecules
-Selectins, bet-2 integrins, ICAM, VCAM, PECAM, ELAM