Lecture 9; Innate Immunity, Inflammation Flashcards
What are the five signs of inflammation?
- Heat (inc. blood flow)
- Redness (Inc. blood flow)
- Swelling (accumulation of fluid)
- Pain (Release of molecules that stimulate nerve endings)
- Loss of function (Multiple causes)
What is inflammation a reaction of?
Inflammation is a reaction of the circulation - serum proteins and leukocytes move from blood to EC space
What is inflammation regulated by?
Vasoactive and chemotactic mediators (i.e chemical gradient exists in the site of inflammation to attract cells)
What assists movement of cells from the vasculature in inflammation?
Increases microvasculature permability - loss of plasma proteins into the tissue
How does inflammation assist cells moving through the endothelium?
Increased expression of adhesion molecules on endothelial cells and release of chemotactic factors from inflamed region- facilitate binding of leukocytes to vessel walls, extravasation and migration to inflamed region
What is the last component of an inflammatory response?
Inflammation resolution
Describe the onset, duration and outcomes of acute inflammation;
Onset - minutes, hours
Duration- few days
Outcomes; Resolution, abscess formation, , chronic inflammation
Describe the causes and primary mediators of acute inflammation;
Causes; Pathogens, injured tissue
Primary mediators; Vasoactive amines, eicosanoids,
What are the cells involved in acute inflammation?
Neutrophils, basophils (inflammatory response)
Eosinophils (response to helminth worms, parasites
Mononuclear cells (monocytes, macrophages)
What is the cause of chronic inflammation?
Persistant inflammation due to;
- Non-degradable pathogens,
- Viral infections,
- Persistent foreign bodies,
- Autoimmune reactions
What are the cells involved in chronic inflammation?
Mononuclear cells;
- Monocytes
- Macrophages
- Lymphocytes
- Plasma cells
- Fibroblasts
What are the primary mediators of inflammation?
Inflam cyotkines
Growth factors
ROS
Hydrolytic enzymes
What is the onset, duration and outcomes of chronic inflammation?
Onset; Delayed
Duration; Months, years
Outcomes; TIssue destruction, necrosis, fibrosis
What cells respond first to inflammation?
Neutrophils
Numbers must be tightly regulated
How can neutrophils contribute to the inflammation response?
Contain secretory granules with pro-inflammatory proteins-e.g. MPO, defensins, lactoferrin, lysozyme, MMP9
(respiratory burst (ROS)
Can eliminate microbes by multiple mechanisms (both intracellular and extracellular)
What are the killing mechanisms of neutrophils?
Phagocytosis
Degranulation
NETs
What are NETs?
Neutrophil extra cellular traps
These can promote inflammation resolution by degrading pro inflammatory cytokines
What is the function of macrophages?
Mature tissue macrophages perform immune surveillance activities (phagocytosis, antigen presentation, immune suppression, clearance of scenscent RBC)
(tissue dependant)
Describe the temporal profile of leukocyte infiltration;
Neutrophils arrive first (hrs), then undergo apoptosis before mononuclear cells (macrophages) arrive (24+hrs)
What controls leukocyte recruitment?
(Rapid) - H2O2 plays a role
Slow) - Leukocyte extravasartion from the vasculature (cytokines
Describe how hydrogen peroxide regulates the immediate recruitment of neutrophils;
Duox protein is expressed on epithelial cells, it is an NAPDH oxidase and in response to wounds there is an influx of Ca into epithelial cells, this activates the Duox protein and it creates H2O2, this creates an H2O2 gradient attracting neutrophils
How do Neutrophils sense H2O2?
Neutrophils express tyrosine kinase Lyn, H2O2 oxidises a residue, this results in a phosphorylation cascade, leading to migration, exactly how is unknown
How is the neutrophil response limited?
Neutrophils dampen the H2O2 response as neutrophil MPO consumes wound derived H2O2 (this in turn dampens the number of neutrophils responding)
Describe leukocyte extravasation from the vasculature;
- Tethering, rolling, adhesion, crawling, transendothelial migration
- Histamine, leukotrienes, cytokines alter endothelial expression of surface adhesion molecules
- Tethering (P-selectin and E- selectin)
- Chemokines activate neutrophil cell surface integrins that bind endothelial ICAMs
- Leukocytes exit blood vessel
(should know this from previous lecture)
