Lecture 5 - chronic inflammation and atherosclerosis Flashcards
nsaAcute inflammation vs chronic inflammation: what they result in
AI - Vascular changes, neutrophil recruitment, and limited tissue injury
CI - Angiogenesis, monocellular nuclear infiltrate, progressive tissue injury, fibrosis (collagen deposition and loss of function)
Acute inflammation vs chronic inflammation: their final resolution
AI resolutions - Either fibrosis, abscess, or full resolution (clearance of injurious stimuli, mediators, and acute inflammatory cells, replacement of injured cells, and regained function)
CI resolutions - Fibrosis (collagen deposition, loss of function)
Acute inflammation vs chronic inflammation: causes
AI - Infarction, bacterial infection, toxins, and trauma
CI - viral infections, chronic infections, persistent injury, autoimmune diseases
Acute inflammation vs chronic inflammation: causes
CI - (Low onset, prolonged period of inflammation (weeks to months)), possible systemic signs, predominantly monocytes/macrophages and lymphocytes, inflammation + tissue injury + repair (fibrosis & angiogenesis)
AI - (Rapid response to infection/injury (minutes to hours), often self-limiting), microbial infections, hypersensitivity reactions, physical foreign bodies, chemicals, and tissue necrosis
The general process of inflammation
Cellular infiltrate, tissue destruction, healing
Macrophages: where do they come from, how long do they last, what are they called in different locations, and what are the two activated forms of macrophages?
Bone marrow stem cells -> monoblast -> monocyte -> macrophage (t½ ~ 24hrs)
In tissue, macrophages can live up to many months
- Alveolar macrophages - in the lungs
- Microglia - macrophages in the brain
- Kupffer cells - macrophages in the liver
- Osteoclasts - macrophages in the bones
Classically activated and alternatively activated
Classically activated macrophages: what activates them and what do they do?
Usually microbial triggers - ie Toll-like receptors - or interferon-gamma (INF-γ) of the cytokines
Pro-inflammatory response:
* Microbial killing function - produces large amounts of ROS, NO, and lysosomal enzymes
* Inflammation- stimulating function - IL-1, IL-12, IL-23, and chemokines promote IF
* Displaying pathogen antigens to T cells
Alternatively activated macrophages: what activates them and what do they do?
IL-13 and IL-4
Anti-inflammatory response:
* Tissue repair and fibrosis stimulated - growth factors and TGF-β
* Anti-inflammatory effects stimulated - IL-10 and TGF-β
Adaptive immunity cycle
- Macrophages activated
- Macrophages become APC
- T cell either is activated or not activated - inactive T cells increase the TGF-γ, activating more macrophages
- Activated T cells activate more chemokines, TNF, and IL-17, recruiting more leukocytes to the area
- Activated leukocytes stimulate more macrophages to be activated
Plasma cells
Present in chronic inflammation, produces antibodies which target antigens that are usually microbial but in some cases (autoimmune) may target self-antigens
Eosinophils: when are they present
Chronic inflammatory diseases - parasites and allergens mainly
Major basic protein
Important in histamine release from mast cells and causing basophils to be released
Toxic to parasites, indirectly causes increased vasodilation and vascular permeability
Mast cells in inflammation
Produce histamines and prostaglandins
Atherosclerosis: what is it, what is produced in people who suffer from atherosclerosis, and where/what are the targets?
A form of arteriosclerosis - thickening of the arterial wall and loss of elasticity
Atheromatous plaques - lesions with a core of lipid covered by a white fibrous cap
Occurs in tunica intima, medium/large sized arteries affected
Classical and ‘new’ risk factors for atherosclerosis
Classical: modifiable and non-modifiable risk factors
‘New’: Inflammatory markers, other miscellaneous