Mechanisms of inflammation Flashcards
Describe the vascular and cellular events
- Controlled by complex web of cellular interactions
- Pro/Anti- inflammatory
Describe the action of cytokines as inflammatory mediators
- Produced at site when required- polypeptides/ glycoproteins, small, low weight
- Bind to receptors of target cells- affected gene transcription via 2nd messengers
- Inflammatory cells, fibroblasts, epithelial cells and endothelial cells secrete
- Release triggered by direct injury or stimulation by other inflammatory cells
Describe mediators of acute inflammation
- Vascular dilation: histamine, prostaglandins and nitric oxide
- Increased vascular permeability- histamine, bradykinins, leukotriene B4, prostaglandins and C5a
- Adhesion of leucocytes to endothelium: IL1 and TNF-alpha
- Chemotaxis of neutrophils: leukotriene B4 and IL8
Describe pro-inflammatory cytokines
- TNF-alpha and IL1
- > Endothelial adhesion molecules
- > Increased coagulation and cytokine secretion
- > Stimulate fibroblasts
- > Systemic effects
- IL6
- > important in systemic effects
- > Acute phase response, pyrexia, haematopoesis
Describe anti-inflammatory cytokines
- IL10
- > Inhibits cytokine secretion
- > Decreased antigen presentation
- TGF- beta (transforming growth factor)
- > Immunological tolerance
- > Released by macrophages
- > Released by myofibroblasts in fibrosis
What is the function of macrophages?
Phagocytosis and co-ordination of immune response
What is the function of mononuclear phagocyte system?
In bone marrow from haemopoietic stem cells, in the blood macrophage=monocyte
Describe antigen presentation
- Endocytosis, fragmentation, MHC Class 2 complex, presented to T cell
Describe B cell action
- Antibodies activated
- Plasma cells,
- Different to lymphocytes- more cytoplasm and perinuclear hoff
Describe T cell action
- Helper- CD4, secrete cytokines, command-and-control of immune system
- Cytotoxic- CD8, kills abnormal cells, viral antigens result in chronic inflammation, immunotherapy involves developing immune system to cure cancer
Describe mast cells
- Granular cytoplasm
- Preformed mediators
- Prostaglandins
- Cytokine release (eosinophil chemotactic factor)
- Significant in allergic reactions
Describe eosinophils
Mediated by IgE (immunoglobin E), allergy and parasitic infection
Describe neutrophils
Phagocyte, acute inflammation, granular cytoplasm (AB proteases, lysozymes, defensins)
- Ideal for bacterial infections
Describe basophils
- Resemble mast cells
- Confined to bloodstream
- Not seen in tissue
Describe endothelial cells
- Polymorphonuclear leucocytes bind to cell adhesion molecules
What are the granular polymorphonuclear leucocytes?
- Eosinophils
- Neutrophils
- Basophils
What colour does each granular polymorphonuclear leucocyte go with eosin stain?
- Eosinophil- pink- graniles have high affinity
- Basophil- dark blue stain
- Neutrophil- in between (neutral)
How does tissue heal after scarring?
- Replace damaged tissue
What does granulation tissue include?
- Endothelial cells
- Myo/fibroblasts
- Acute inflammation cells
- Macroscopic- red (very vascular) and granular surface
- Microscopic- capillaries, myofibroblasts and macrophages
- Collagen
Describe the maturation of granulation tissue in fibrosis
- Inflammatory cells leave
- Collagen increases
- New blood supply (fewer capillaries required)
- Dense fibrous tissue
Describe the function of granulation tissue in fibrosis
- To produce a scar
- Scar restores physical integrity of body
- Regulated by cytokines- TGF-beta is important for production of collagen
What are the positives of fibrosis?
Restored structural integrity
What are the negatives of fibrosis?
- Lack of function of normal tissue
- Acellular
- Cosmetic
- Complications
What are the complications involved in fibrosis?
- Stricture
- Scarring in lumen results narrowing that requires surgical treatment
