Inflammation Flashcards
What is the components and function of inflammation?
Components: vasodilation, oedema formation, leukocyte accumulation and pain
Function: destroy, dilute and partition off the injurous agent so the body can start to heal, tissue repair and tumour rejection
What are the benefits of inflammation?
- Stimulation of immune response: inflammatory cell recruitment, dilute bacterial toxins, inflammatory exudate gets into the lymph nodes
- Increase vascular permeability: allows entering of antibodies and complement components - opsonisation of microorganisms leading to lysis of phagocytosis
- Delivery of nutrients and oxygen: aided by increase fluid flow through the area
- Fibrin formation: fibrinogen forms fibrin mesh which can trap microorganisms
- Mediator and drug transport: fluid carries mediators and drugs to site where bacteria is multiplying.
What are the detrimental effects of inflammation?
- Digestion of normal tissues: collagen eases and other proteases digest normal tissues -> tissue damage and destruction and vascular damage
- Swelling: inflammatory swelling - serious in enclosed space
- Inappropriate and prolonged inflammatory response: allergic inflammatory responses may be life-threatening.
Describe the process of leukocyte migration into infected tissues
- Leukocyte adhesion
- Micro vessel transmigration
- Granulocyte chemotaxis- eosinophil and basophils have chemotaxis ability
- Phagocytosis -> generate reactive oxygen species (oxygen burst) -> anti microbial -> degranulation (release anti-microbial cytotoxic)
- Oxygen burst induces apoptosis -> gets eaten by macrophage
Which types of cells can produce agents that can kill/suppress microbial growth but uncontrolled release can damage healthy tissue cells?
Macrophages
Eosinophils
Neutrophils
Where do neutrophils mature? What are their primary functions?
Neutrophils mature in the bone marrow - three maturation process - terminally differentiated
Primary functions:
- Recognise and respond to chemical signals generated in the inflamed tissue (chemotaxis)
- Adhere to activated endothelium
- Migrate to site of infection
- Recognise invading organism
- Phagocytise/ destroy the organism
What are the defence mechanisms of neutrophils?
- Phagocytosis of the invading microorganisms
- Reactive oxygen species generation through the activity of NADPH oxidase that generates superoxide anion
- Release of granule enzymes into phagolysosome and surrounding environments
- Generation of neutrophils extracellular traps (generation of mesh work made from decondensed chromatin and histones protein to effectively trap pathogen)
What are the inflammatory mediators release by neutrophils?
Stored: IL-8
Or
Newly synthesised: PAF, LTB4
What is the beneficial effect of priming and activating neutrophils? What are the two mediators responsible for this priming and activation?
Priming neutrophils enhance its phagocyte ability.
Whilst activating neutrophils allows it to generate more reactive oxygen species to kill the phagocytise pathogen.
The two mediators responsible for this are PAF (priming) and PAF + fMLP (for activation)
What is the role of eosinophils? What are the primary functions and its defence mechanisms of eosinophils?
Eosinophils is responsible for destruction of invading parasites. It is involved in allergic disease of the eye, lung, nose and skin
Defence mechanism:
-granules: released to destroy pathogens
Specific granules:
- major basic protein
- eosinophil cationic protein
- eosinophil peroxidase
- eosinophil derived neurotoxin
Small granules:
- acid phosphatase
- B-glucoronidase
Describe the defence mechanisms of mast cells
Granules - mediators (e.g. histamine) can be released to regulate a number of processes
Receptors: bind IgE via IgE receptors. This triggers rapid activation and release of granule contents
List down chemical mediators released and plasma factors that is released during ACUTE INFLAMMATION
Chemical mediators:
- histamine
- serotonin (5-HT)
- platelet activation factor (PAF)
- prostaglandins (PGI2, PGE2)
- Leukotriene (LTB4, LTC4)
- cytokines and chemokines
Plasma factors:
- complement factors (e.g. C5a, C3a)
- kallikrienes (bradykinin)
- coagulation factors
- fibrinolytic factors
What stimulates the release of histamine? And which receptors does histamine bind to?
Complement components (C3a and C5a) or when antigen interacts with cell fixed IgE
Histamine binds to H1,2 and 3 receptors
What are the main actions in humans when histamine binds to its receptor?
H1
- vasodilation of smooth muscle except in blood vessels
- cardiac stimulation
- increased vascular permeability
H2
-stimulates gastric acid secretion
How are Eicosanoids formed?
Eicosanoids are formed from oxidation of Arachidonic acid by different enzymes which would yield different types of Eicosanoids