Acute Inflammation Flashcards
Acute inflammation phases
- Stimulus
- Mediators
- Vascular
- Cellular
- Repair/resolution
Phase 1
Stimulus: The initial cause of the inflammatory response, such as a thorn penetrating the skin, causing cell necrosis and introducing pathogens.
Phase 2
Chemical Mediator Release: Immune cells like macrophages, mast cells, or dendritic cells near the injury release mediators (e.g., histamines, prostaglandins, cytokines) in response to pathogens or damaged cells.
Phase 3
Vascular Phase: Chemical mediators affect neighboring blood vessels, causing vascular dilation and endothelial shrinkage. This results in increased blood flow (leading to heat and redness) and makes the blood vessels leaky, allowing more fluid into the tissue (causing swelling and pain).
Phase 4
Cellular Phase: Immune cells, primarily neutrophils and macrophages in the case of acute inflammation, migrate out of the blood vessels to the site of injury. They phagocytose (engulf and digest) damaged cells and pathogens, clearing the area. Neutrophils undergo apoptosis and macrophages clean up (efferocytosis).
Phase 5
Repair or Resolution: Additional blood vessels grow into the area (angiogenesis from TGF-b), bringing repair cells like fibroblasts, which close off the site. The outcome is either repair of the tissue or resolution of the inflammation.
What chemicals are released during an acute inflammatory response and what releases them?
Mast cells, macrophages, dendritic cells release histamines, prostaglandins and cytokines
Differences between macrophages and neutrophils
neutrophils = short-lived cells that respond to infection via complement system, granule release or phagocytosis; recognize microbial products
macrophages = long-lived cells that provide a warning of infection (MHC presentation) and recruit neutrophils via cytokines; phagocytose dead neutrophils
What are cytokines and where are they released from?
Cytokines are a protein released to either promote inflammation or be anti-inflammatory
Cytokines are released by different WBCs (leukocytes) - Eosinophils, Mast cells and Basophil, Monocytes and Lymphocytes
Name important cytokines
TGF-beta - Transforming growth factor beta
IFN-y - Interferon Gamma
IL-4 & IL-13 - Interleukin 4 and 13
Prostaglandin
What role do cytokines play in local inflammation
Cytokines tell cells where to go and what to do. For example, cytokines can direct immune cells toward an infection site so the cells can fight germs there. They can heighten or lessen the processes associated with inflammation.
What role do cytokines play in systemic inflammation
They send out alerts for help, they recruit other immune cells (neutrophils), increase blood flow to the area, cause a fever, tell liver to produce proteins that fight against infection
Prostaglandins origin, role and what medication to mediate
Arachidonic acid is released from the phospholipid layer of a cell with the help of phospholipase A2 enzyme. Arachidonic acid is then catalyzed by the cyclooxygenase process COX-1 & COX-2 to make Prostaglandins H2.
Medication: Aspirin and NSAIDS will prevent COX-1 and COX-2 from occurring.
Their role is inflammation:
Vasodilation, increase vascular permeability and sensitise nerve endings to pain.
Fever: Act on hypothalamus to raise body temperature set point in response to pyrogens (fever inducing organic substance).
Transforming growth factor beta origin and roles
Released by many immune cells (t cells, macrophages, b cells, fibroblasts)
Promotes tissue repair and stimulates collagen production. Regulates inflammation. Overactive TGF beta can lead to excessive scar tissue or fibrosis in various tissues.
Interleukin 4 & 13 origin and roles
Promote Th2 (t helper) responses (adaptive immunity) to fight off parasitic infections but also plays a role in allergic reactions and asthma.
interferon gamma origin and roles
Activate macrophages (potent activator or marcophages, enhancing their ability to destroy pathogens and tumor cells) although may lead to increased inflammation relevant in rheumatoid arthritis and other disorders.
Can contribute to muscle wasting and inflammation, particularly in chronic diseases with high levels of systemic inflammation.
Regulates immune responses, promoting th1 response.
T helper 1, T helper 2 & T helper 17
T helper 1 are involved in immunity against intracellular microbes.
T helper 2 are involved in immunity against large multi-cellular pathogens like parasites (predominant in allergies)
T helper 17 are involved in immunity against extracellular microbes. Involved in autoimmune & inflammatory disorders (IBD, MS, psoriasis)
What releases prostaglandins?
Macrophages, endothelial cells, fibroblasts, mast cells
What do prostaglandins do to the body?
Vasodilation and increase vascular permeability allowing liquid out of cell, and make nerve endings more sensitive (pain & swelling, redness)
Fever - tell hypothalamus to raise body temperature set point