Inflammation

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