Definition
Response of body to injury
Process
Vascular Phase
- redness, heat & swelling
- transient vasoconstriction after injury
- then vasodilatation of arterioles
- increased permeability followed by plasma exuded into extravascular space
Cellular Phase
- leukocytes adhere to endothelium
- margination - migrate into extravascular space
Inflammatory Cells
Neutrophils
- attracted by chemotactic agents
- phagocytose bacteria, immune complexes & particulate matter
- particulate matter may be opsonised (coated with complement or IgG)
- opsonisation helps phagocytosis by aiding recognition
- during phagocytosis particle encased by vacuole
- lysosomes fuse with vacuole and enzymes destroy particle
Eosinophils
- Involved in host defence from parasitic infections
Mast Cells & Basophils
- involved in allergic or immediate hypersensitivity reactions
Macrophages
- important in chronic inflammation
- produced as monocytes in bone marrow
- function to phagocytose matter and present antigens to T Cells
Lymphocytes
- identify antigens
- help eliminate these antigens
- B Cells become plasma cells - humoral immunity (antibodies)
- T Cells mediate cellular immunity
Mediators
Complement functions
1. Activation of inflammatory cells
2. Cytolysis of infected cells / insert pores
3. Opsonisation of antigen to facilitate phagocytosis
Kinins
- proteins that circulate in plasma in inactive form
- increase permeability blood vessels / Vasodilatation
- hypotension / pain / leukocyte margination
Vasoactive Amines
Histamine
- stored in mast cell granules
- released on activation by IgE
- produces increased BV permeability / vasodilation / bronchospasm
Serotonin
- stored in platelets
- causes vasoconstriction / increased BV permeability / fibrogenesis
Prostaglandins
Arachidonic Acid
- AA is a fatty acid found in most tissues
- released by phospholipases
Prostaglandins
Cyclo-oxygenase (COX) catalyses AA to PGG
- many types
- PGI2 (Prostacyclin) / Thromboxane A / PGE2
Effects of PGE2 & PGI2
- vasodilation
- increase BV permeability
- stimulate osteoclastic bone resorption
- anti-inflammatory effects
- inhibit T Cell activation
- inhibit B Cell proliferation
- inhibit IL-2 production
TXA2
- stimulates platelet aggregation
Leukotrienes
Lipoxygenase catalyse conversion of AA to Leukotrienes
- important mediators
1. Chemotactic for leukocytes
2. Activate neutrophil enzyme secretion
3. Increase BV permeability
4. Cause bronchospasm
Regulation
1. NSAID
- inhibit COX activity / inhibits PG synthesis
- suppress inflammation
- explains many of its side effects
- decrease cytoprotective effect of PGE2 on gastric mucosa (ulcers)
- increase leukotrienes (bronchoconstriction)
2. COX 2 selective
- don't inhibit COX 1
- maintain production of PGE2 in gastric mucosa
2. Glucocorticoids
- inhibit release of AA from phospholipids
- inhibit production of leukotrienes AND prostaglandins
Growth Factors / Cytokines
Polypeptides that regulate inflammatory cells
- Interleukins
- IL-1, IL-6 & TNF
- similar actions
- produced by monocytes
Effects
1. Pyrogenic
2. Stimulate synthesis of Acute Phase Reactants
3. Facilitates B & T Cell proliferation
4. Stimulate stem cell growth for neutrophils & monocytes
IL-2 & IL-4
- stimulate proliferation of T Cells & IG production
- stimulate fusion of macrophages to form MNGC (multinucleated giant cells)
Il-3, Il-5 & Il-7
- promote growth & differentiation of haemopoietic stem cells
Interferons
Interferon Gamma
- produced by activated T cells
- induces expression of Type II MHC antigens
- activates macrophages for antigen presentation
Neutral Proteinases
Acid Proteinases
- most stored in lysosomes of leukocytes
- degrade microbes & cell debris at low pH within phagolysosomes
- degrade extracellular proteins in connective tissue at neutral pH
1. Metalloenzymes
- require metal ions (eg Zn) as cofactor
2. Serine Proteinases
- collagenase - degrades extracellular collagen
- gelatinase - degrades denatured collagen
- proteoglycanase - degrades PG