Dr. Nguyen

• Sialyl-Lewis X-modified proteins
• roles--rolling

• Sialyl-Lewis X-modified proteins
• roles--rolling and adhesion

• L-selectin
• roles: Rolling (neutrophils, monocytes)

• CD11/CD18 integrins (LFA-1, Mac-1)
• roles: firm adhesion, arest, transmigration

• VLA-4 integrin
• roles: Adhesion

• CD31 (homotypic interaction)
• roles: Transmigration of leukocytes through endothelium.

• cells (histamine, serotonin, prostglandins, leukotrienes, platelet-activating factor, ROS, NO, cytokines [TNF, IL-1, IL-6], chemokines)
• plasma: synthesized in liver (complement, kinins, and proteases activated during coagulation)

• preformed mediators in secretory granules: histamine, serotonin (from mast cells, basophils, platelets)
• newly synthesized: prostglandins, leukotrienes, platelet-activating factor, ROS, NO, cytokines, neuropeptides (from leukocytes, mast cells, EC, macrophages, lymphocytes, nerve fibers)

• complement activation: C3a and C5a (anaphylatoxins), C3b, C5b-9 (membrane attack complex)
• Factor XII (Hageman factor) activation: Kinin system (bradykinin), coagulation/fibrinolysis ystem

• From mast cells, basophils, platelets
• vasodilation, increased vascular permeability, endothelial activation

• from platelets
• vasoconstriction

• from mast cells and leukocytes
• vasodilation, pain, and fever

• from mast cells and leukocytes
• increased vascular permeability, chemotaxis, leukocyte adhesion and activation

• from leukocytes and mast cells
• vasodilation, increased vascular permeability, leukocyte adhesion, chemotaxis, degranulation, oxidative burst, bronchoconstriction

• from leukocytes
• killing of microbes, tissue damage

• from endothelium and macrophages.  
• vascular smooth muscle relaxation, killing of microbes.

• from macrophages, endothelial cells, and mast cells
• local: endothelial activation (expression of adhesion molecules).  Systemic: fever, metabolic abnormalities, hypotension (shock). They are proteins that modulate the function of other cell types. They bind to specific receptors on target cells.

• from leukocytes and activated macrophages
• chemotaxis and leukocyte activation

• from plasma
• leukocyte chemotaxis and activation, direct target killing (MAC), vasodilation (mast cell stimulation)

• from plasma
• increased vascular permeability, smooth muscle contraction, vasodilation, pain

• Cyclooxygenase pathway
• lipoxygenase pathway

• from plasma
• endothelial activation, leukocyte recruitment

prostglandins and thromboxanes

leukotrienes and lipoxins

• Vasodilation
• potentiates inflammation
• inhibits platelets
• pain
• fever

• vasoconstriction
• platelet aggregation

• vasoconstriction
• bronchospasm
• increase vascular permeability

• inhibit inflammation
• decrease leukocyte chemotaxis

corticosteroids

NSAIDS

• complement system
• kinin system
• clotting factor system

• Assembly of the MAC (membrane attack complex) with lysis of offending agent.  Two mechanisms:
• -classical pathway (cytokines and endotoxins...NO and ROS kills ingested organisms, stimulates inflammation)
• -alternate complement pathway (not actively microbicidal, involved in tissue repair, promote angiogenesis, activate fibroblasts, collagen synthesis)

opsonization

• Anaphylatoxin
• mast cell degranulation
• increase in vascular permeability

• Anaphylatoxin
• mast cell degranulation
• increase vascular permeability
• **ACTIVATES ARACHIDONIC ACID PATHWAY 
• CHEMOTACTIC FOR LEUKOCYTES

• Intrinsic pathway-consists of plasma proenzymes which can be activated by Hageman factor, results in activation of thrombin, cleavage of fibrin and generation of fibrin clot
• Extrinsic pathway

• Tissue infiltration by mononuclear cells--macrophages, lymphocytes, plasma cells
• Tissue destruction--induced by products of inflammatory cells
• attempts at repair--CT replacement, angiogenesis, fibrosis

Kupffer cells

sinus histiocytes

microglial cells

• ROS, NO, Lysosomal enzymes-->leads to microbicidal actions, phagocytosis and killing of many bacteria and fungi
• IL-1, IL-12, IL-23, and chemokines-->inflammation

• Growth factors, TGF-beta-->Tissue repair and fibrosis
• IL-10 and TGF-beta-->Anti-inflammatory effects

• resolution/regeneration/restitution of normal structure
• repair/organization/healing by CT/fibrosis/scarring
• It can continue indefinitely...i.e. rheumatoid arthritis

• CRP: C reactive protein
• SAA: Serum amyloid A
• ESR: Erythrocyte Sedimentation rate
• Leukocyte count:neutrophilia, eosinophilia, lymphocytosis, lymphopenia

loss of weight, muscle atrophy, fatigue, weakness, and significantloss of appetite in someone who is not actively trying to lose weight. The formal definition of cachexia is the loss of body mass that cannot be reversed nutritionally: Even if the affected patient eats more calories, lean body mass will be lost, indicating a primary pathology is in place.

cyclosporin A emulsion