4. Inflammation and Inflammatory Mediators Flashcards
What is acute inflammation?
A protective response in innate immunity
often, but NOT always, caused by infection - sometimes trauma
terminology by -itis
What are the local signs of inflammation?
P- Pain
R- Redness
I- Loss of mobility
S- Swelling
H- Heat
What triggers inflammation?
Pathogens or damaged tissue
Both contain molecules that pind to PRRs on complement and sentinel cells
Sentinel cells being macrophages, dendritic macrophages and mast cells
What are PAMP’s/DAMP’s
Pathogen associated-molecular patterns
Damaged associated molecular patterns
What are the mechanisms of inflam?
sent cells prod mediators that promote bloodflow, attract cells and PMN’s and improve phagocytosis, also vasodilation, increased capillary permeability, increased sensitivity to pain
How does the mechanisms of inflamation cause vasodilation and increased capillary permeability + sensitivity to pain
Vasodilation - histamines + prostaglandins released by macros, mast, and neutrophils. Inc blood flow. Sign is redness/heat
Inc capill permeability to histamine and prostaglandins, exudation of fluids. Sign is swelling.
Inc sensitivity to pain = loss of func
In regards to the mechanism of inflam, what is the initial predominant inflam cell?, what is it further activated by and stimulated to?
Neutrophils the initial predom inflam cell. Attracted by mediators from activated complement and sentinel cells which attach to endothelium of caps and crawl via diapedesis. Activated by binding pathogens or damaged tissue at their PRRs and products of activated complement. Stimulated to phagocytose and kill ingested material. Pus is formation of dead neutrophils, cells and bacteria
How does the activation of clotting work?
Proteins in exudate include clotting factors and fibrinogen. Activated by damaged/leaky tissue. Fibrin is formed, act as net to trap pathogens, may form capsule around site of inflam.
Abscess = pus trapped in capsule
What is chronic inflamation
When neutrophils decreased and macrophages and lymphocytes dominate in tissue - #’s in blood increase
fibrous tissue is prod
What cells initially trigger the inflame response? (Sentinel cells), what do they respond to?
Macrophages, dendritic cells and mast cells.
PAMPs and DAMPs, complement and prostaglandins, histamines
What is a quick summary of healing
insult is removed by phagocytosis and killing. Inflam mediator prod and inflam stops
damaged tissue replaced by new tissue and scar tissue (fibrous tissue)
What does the systemic response look like? What are other systemic responses?
In moderate and severe inflam there is whole body response - especially likely in bact/viral infections
Removal of trace nutrients from body (Ex Iron), low iron and fever works together, reduced appetite, breakdown of muscle to fuel body - harmful is prolonged
What are blood neutrophils?
In very severe inflam the # of neutrophils in blood may initially dec as they move to site of inflam. Bone marrow inc prod in response to inflam - PMN count in blood inc, usual response to moderate inflam
Mild inflam does not prod a change in blood count
What is fever? How does it work?
Interleukins and tumor necrosis factor (endogenous pyrogen) is released from sentinel cells. Acts upon hypothalamus. Prostaglandin mediated. Inc ‘set point’, shown by shivering, huddling, raised hair coat. Directly inhibs growth of some pathogens. Also enhances the activity of neutrophils, macros and T-Lymphocytes
What are acute phase proteins?
Liver is stim to prod proteins - acute phase reaction proteins ( proteins necessary for/part of local inflam response) soluble PRRs, complement components, clotting molecules and iron binding proteins
Part of clotting system - fibrinogen, prothrombin. Remove iron (ferritin, ceruloplasmin), some compl. system proteins (lectin pathways), opsonize microbes, recruit immune cells to inflame site. Proteins help degrade inflam products, plasminogen breaks down blood clots and downregular(control) inflam
