*OBJ - Mediators of Inflammation Flashcards
Inflammation in basic terms
1) Margination & rolling
2) Adhesion & trasnmigration
3) Chemotactic-driven migration (bacteria)
4) Recognition & attachemnt
5) Engulfment & phagocytosis
6) Killing & degradation
Know what are the important mediators of inflammation and what their roles are in the inflammatory process.
a
Be familiar with the major congenital and acquired alterations in inflammation, and understand why any defects in the process of inflammation have such serious consequences.
a
Describe the systemic effects of inflammation, and how these are regulated.
a
Discuss the role of mediators in different inflammatory reactions.
a
Events in Mediation & places there are mediators
- Vasodilation
- increased vascular permeability
- Chemotaxis, leukocyte recruitment, activation
- Fever
- Pain
- Tissue Damage
Locally/Cell Derived mediators
@ site of inflammation:
- synthesized de novo (Prostaglandins & cytokins)
- preformed & secreted (i.e. histamine in Mast cell granules; Ex: Intracellular granules in neutrophils, macrophages, mast cells & Platelets)
Systemically/Plasma derived
- made in liver & present in plasma as precursors that need to be activated (proteolysis)
i. e. complement or kinins
**tight regulation with short half life, inactivated by enzymes & eliminated by antioxidants
Histamine & Serotonin
preformed granules & released early in Acute Inflammation
Effect:
- dilation of arterioles
- increased vascular permeability
- platelet aggregation(triggered by ECM/collagen/thrombin)
Made by: mast cells, blood basophils & platelets
Triggered by:
- trauma, cold, heart
- IgE (allergy/asthma/hemeliths)
- C3a, C5a
- substance P (neutropeptide)
- IL-1 & IL-8
Arachidonic Acid Metabolites
Prostaglandins, Leukotrienes & Lipoxins
-Eicosanoids (AAs) synthesized @ inflammation side by WBC, mast cells, platelets & endothelial cells
2 Major pathways:
1) Cyclooxygenase => PG
2) Lipooxygenase => LT/Lipoxin
Steroids: antiinflammatory by inhibiting phosphlipases that make Arachadonic acid
NSAIDS (ASA/Indomethacin) inhibit COX 1/2(Cyclooxygenase) production of PG; antiplatelet aggregation; risk for GI bleed
Cyclooxygenase Pathway
a
Platelet Activating Factor (PAF)
a
Cytokines/Interluekins
TNF, IL-1 & IL-6
Lipooxygenase Pathway
a
Chemokines
CC chemokines
CXC (IL-8) chemokine
